DISCLAIMER

Any questions you may have about legal information within this article should be discussed with your attorney or legal counsel at your institution. SPIRIT is an educational resource ONLY and is not meant to substitute research ethics oversight or approval.

I met Dr. Parente (of course) through LinkedIn

Janice Parente has spent more than thirty years advocating for the rights, safety and welfare of research participants, working to strengthen protections and advance human research accreditation in Canada.

Janice is the author of Ethics on Trial: Protecting Humans in Canada’s Broken Research System (Dundurn Press, 2025), which examines the structural governance failures that have allowed unethical research practices to persist. She is currently writing her second book, They Came Seeking Care: Inside Canada’s Quiet Return to Unethical Human Experimentation, scheduled for publication by Dundurn Press in 2027.

Born in Hamilton, Ontario, Janice earned a B.Sc. in biochemistry from McMaster University, followed by a Ph.D. in medicine (molecular pharmacology) at the University of Alberta and a postdoctoral fellowship at the University of Calgary.

Janice is the proud mother of two daughters - both women in STEM pursuing postgraduate degrees. She lives with Olivia, her South Korean rescue dog, on a peaceful lake in the Quebec Laurentians.

She began her career in clinical research within the pharmaceutical industry and, in 1992, founded a research company that grew into two successful operating companies: ethica CRO and Veritas IRB.

She later established two non-profits dedicated to Canadian human research accreditation and national standards development: HRA Canada and HRSO.

HRA Canada is an independent, not-for-profit accrediting body for human research

It accredits Canadian Human Research Protection Programs (HRPPs) through a bilingual, voluntary, affordable, peer-driven program based on international and national standards for human research.

HRSO is a Canadian, not-for-profit, human research standards development organization

Adherence to human research standards ensures that the rights and welfare of research participants are safeguarded and that the research is conducted in a responsible manner in an environment that promotes risk management and reliable, verifiable, and credible data.

Q1: Why did Canada need a distinct HRPP accreditation model? Does this differ from the U.S. AAHRPP accreditation model?

It was clear back in the early 2000s that Canada absolutely needed an HRPP accreditation program. The question was whether the existing American model was the right fit for Canadian institutions.

The AAHRPP program never gained wide acceptance in Canada. It was developed within the context of the U.S. regulatory and research environment, and many Canadian institutions viewed it as an imported model. It was also a significant undertaking, making it difficult for many organizations to justify the cost and resources required for accreditation.

We therefore set out to develop one that would be recognizably Canadian, accessible to Canadian institutions, and grounded in the framework they already knew and trusted.

The natural starting point was the Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans (TCPS 2). It is Canada’s principal normative research ethics document and is widely accepted by researchers, REBs (or IRBs), institutions, and funders. Rather than asking organizations to adopt a different ethical framework as the basis for accreditation, the Canadian model built on one they already valued, translating its principles into assessable National Standards of Canada.

The Canadian model also differs structurally from AAHRPP. The Human Research Standards Organization (HRSO) is a standards development organization. It develops and maintains the National Standards of Canada for human research through a consensus-based standards development process involving thousands of Canadian stakeholders from every region of the country. HRA Canada is a separate organization that assesses and accredits HRPPs against those standards. This separation is intentional: the organization that develops the standards is not the organization that determines whether an institution conforms to them.

My perspective comes from direct experience with both models. My operating companies, ethica CRO and Veritas IRB, were accredited by AAHRPP for many years before later becoming accredited by HRA Canada. AAHRPP is an excellent organization and a true pioneer in advancing the principle that protecting research participants is an institutional responsibility, not solely the responsibility of the REB.

The Canadian model was never intended to diminish or compete with AAHRPP. International research sponsors and funders, as well as the Canadian government, recognize the two accreditation models as equivalent. They are different routes to the same destination: demonstrating that an organization has a mature, institution-wide system for protecting the people who participate in research.

Q2: What does a truly institution-wide culture of research participant protection look like in practice?

A mature culture of participant protection isn’t demonstrated by having perfect policies or hoping the site reviewers don’t find anything. Quite the opposite. Organizations with strong HRPPs welcome external review because they see it as another opportunity to learn and improve. They understand that quality assurance is not about finding fault; it’s about strengthening the systems that protect research participants.

Organizations with a strong culture invest in education rather than treating training as a compliance exercise. They welcome quality assurance instead of viewing it as criticism. They understand the ethical distinction between caring for patients and conducting research with participants. Even their language reflects their values - they speak about research participants, not patients or subjects. Language matters because it reflects how an organization sees the people who make research possible.

They foster an environment where people feel safe raising concerns about the conduct of research. Individuals who report concerns in good faith are protected from retribution, and, whenever possible, their anonymity is respected. Organizations with a mature culture understand that speaking up is not an act of disloyalty - it is an essential part of protecting research participants.

And perhaps most importantly, they are willing to challenge sponsors or clients when participant protection is at stake, even if doing so risks future business.

Ultimately, a culture of participant protection is evident when an organization asks, “How can we do this better?” rather than, “How do we prove we’ve done enough?” If it is continuously asking questions, auditing itself, learning from mistakes, and welcoming independent feedback, accreditation simply confirms a culture that already exists.

Q3: How do you evaluate something intangible like culture during accreditation?

Culture may be intangible, but it isn’t invisible. During an accreditation site review, you see it in how an organization responds when things don’t go according to plan. Errors, misunderstandings, and difficult decisions often reveal far more about an organization’s culture than its written policies ever could.

One example is when an investigator conducts a project believing it to be quality improvement, only to discover later that it should have undergone REB review. Almost every experienced HRPP will eventually encounter a situation like this. The question for an accreditor isn’t whether the mistake occurred. The question is how the organization responded.

Did it look for someone to blame? Did it attempt to minimize the issue or rationalize what happened? Or did it ask why the misunderstanding occurred, whether its guidance was sufficiently clear, whether additional education or training was needed, and what changes could prevent a similar situation in the future?

The incident itself tells us very little about culture. The response tells us almost everything.

That’s why accreditation isn’t about finding organizations that never make mistakes. Every HRPP will encounter difficult situations. What distinguishes a mature organization is its willingness to examine what happened, learn from it, strengthen its systems, and share those lessons. Culture is reflected not in the absence of problems, but in the commitment to continuous improvement.

Q4: HRSO standards are positioned as national standards. How do the HRSO standards differ fundamentally from other guidance such as ICH GCP E6(R3)?

I think the first thing to clarify is that normative documents and standards, such as HRSO’s National Standards of Canada, serve different purposes.

Normative documents, such as ICH GCP E6(R3), provide guidance. They explain the principles that should govern research, why those principles are important, and the practices organizations should strive to achieve. Because they provide guidance rather than requirements, organizations may reasonably interpret and implement them differently. That flexibility is one of the strengths of normative documents, but it can also result in differences in how organizations implement the same guidance.

A National Standard of Canada serves a different purpose. It does not duplicate the guidance contained in normative documents. Rather, it establishes clear, measurable, and assessable requirements developed through a consensus-based standards development process that considers the guidance contained in relevant normative documents. A standard identifies what is required for conformity while allowing organizations the flexibility to determine how those requirements are best achieved within their own environment.

That distinction is important. When organizations conform to the same requirements, they can have confidence in one another’s systems and processes. Researchers, institutions, sponsors, and funders know they are working from a common set of expectations, even though individual organizations may implement those requirements in different ways. That consistency strengthens collaboration, reduces unnecessary duplication, and ultimately enhances the protection of research participants.

Another important feature of HRSO’s National Standards of Canada is that they are living documents. They are reviewed and maintained annually through the consensus process to ensure they remain current as normative documents evolve and new best practices emerge. This allows accredited organizations to conform to requirements that reflect the current state of knowledge and practice, rather than a point in time.

Q5: What blind spots do organizations most commonly discover during the accreditation process?

One of the most common blind spots, particularly in Canada, is the assumption that the REB is the system that protects research participants.

It is not, and it was never intended to be.

The REB is a critically important component of an HRPP, but it cannot, by itself, protect research participants. Participant protection depends on many parts of the organization working together, including investigators, research administration, contracts, privacy, legal counsel, pharmacy, information technology, quality assurance, institutional leadership, and others. An effective HRPP recognizes that protecting research participants is a shared organizational responsibility.

For many organizations, this represents a significant cultural shift. Canadian REBs have historically been told, and have come to understand, that they constitute the system of human research protection. They have therefore carried much of the responsibility for participant protection and understandably take great pride in that role. HRPP accreditation does not diminish the importance or independence of the REB. Rather, it recognizes that the REB cannot and should not be expected to carry that responsibility alone.

This blind spot extends beyond organizations undergoing accreditation. In my view, it remains embedded in the approach taken by Health Canada and the Canadian Institutes of Health Research. Both continue to place extraordinary reliance on the REB as the system of protection, while REBs themselves generally remain unchecked, unaudited, unverified, and unaccountable to any independent body. Ethical review is essential, but ethical review alone is not a human research protection system.

Changing this understanding - turning that ship - is often the greatest hurdle in the accreditation process. It requires the REB to recognize that responsibility must be shared, and the rest of the organization to accept responsibilities it may previously have left to the REB.

Once that shift occurs, organizations begin to identify opportunities to strengthen education, quality assurance, institutional oversight, leadership engagement, and collaboration across the entire HRPP. That is not simply a change in organizational structure. It is a change in culture: from relying on a committee to protect participants to building an institution-wide system that does so.

Q6: What does meaningful research participant protection look like from the participant’s perspective?

The best human research protection programs are invisible to the people they protect.

Research participants should not have to think about whether an organization has good policies, an effective REB, or a mature quality assurance program. They shouldn’t have to wonder whether staff are properly trained or whether the institution has appropriate oversight. All of those systems should work together quietly in the background.

From the participant’s perspective, protection is experienced rather than observed. They understand what they are being asked to do. They are treated with dignity and respect. Their questions are welcomed and answered honestly. Their privacy is protected. If new information becomes available, it is shared. If concerns arise, they know they will be heard without fear or hesitation.

The participant should never have to compensate for weaknesses in the organization’s systems. They should never bear the consequences of poor communication, unclear responsibilities, or inadequate oversight. Those are institutional responsibilities.

When a human research protection program is functioning well, participants may never know it exists - and that is exactly as it should be.

The best participant protection is the protection research participants never have to think about.

Q7: If you could redesign the global human research protection system from scratch, what would you do differently?

I wouldn’t begin by redesigning REBs. I would begin by recognizing that protecting research participants is an institutional responsibility, not the responsibility of a single committee.

For too long, many organizations have viewed participant protection primarily through the lens of ethics review. Ethics review is essential, but it is only one component of a mature HRPP. Truly effective participant protection requires leadership commitment, clearly defined organizational responsibilities, education, quality assurance, continuous improvement, and a culture in which everyone understands that protecting research participants is part of their role.

I would also ensure that organizations were assessed against clear, consensus-based standards rather than relying solely on guidance documents or assumptions about what constitutes good practice. Standards provide measurable requirements while allowing organizations the flexibility to implement them in ways that best suit their environment. They also create a common foundation that allows organizations, sponsors, funders, and participants to have confidence in one another’s systems.

Finally, I would build continuous learning into the system itself. No organization is perfect, and no human research protection system should be expected to be static. Organizations should welcome quality assurance, learn from mistakes, encourage people to raise concerns without fear of retribution, and continually strengthen the systems that protect research participants.

Ultimately, I don’t think the global human research protection system needs to be reinvented. It needs to be understood differently. When organizations recognize that participant protection is an institutional responsibility rather than the responsibility of a single committee, they begin to build systems that are stronger, more resilient, and more deserving of the public’s trust.

Research participants deserve more than ethical review. They deserve organizations that have made their protection everyone’s responsibility.

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Any questions you may have about legal information within this article should be discussed with your attorney or legal counsel at your institution. SPIRIT is an educational resource ONLY and is not meant to substitute research ethics oversight or approval.

Anthropic used its January healthcare and life sciences announcement to formalize something research teams have been circling for a while: giving an AI model structured access to the clinical trial ecosystem itself, not just the literature about it1.

The piece most relevant to protocol writers and IRB-adjacent staff is the new ClinicalTrials.gov connector.

It links Claude to the NIH/NLM registry’s API, which now holds roughly 500,000 registered trials across 221 countries and territories. Practically, that means six underlying functions: searching trials by condition, intervention, location, sponsor, status, or phase; pulling full protocol details (eligibility criteria, endpoints, enrollment targets) for a specific NCT number; profiling a sponsor’s full trial portfolio; identifying investigators active in a therapeutic area; comparing endpoints across multiple studies; and screening eligibility language against specific demographic or clinical criteria.

For the people who actually staff protocol design and regulatory ops, the stated use cases track closely to real workflow pain points: benchmarking primary endpoints against everything else registered in a therapeutic area, drafting eligibility criteria against precedent studies, and tracking a sponsor’s phase progression for regulatory strategy. None of that replaces judgment. It compresses the discovery phase that used to eat a day of a research coordinator’s week.

The broader announcement situates this inside a larger build-out: a parallel HIPAA-ready “Claude for Healthcare” offering with connectors to CMS coverage data, ICD-10, and NPI registries, plus additional life sciences connectors to Medidata, bioRxiv/medRxiv, Open Targets, and ChEMBL, among others. Anthropic frames the throughline as speeding up prior authorization, care coordination, and regulatory submissions. Whether that promise holds up under real institutional workflows is the more interesting question for those of us doing this work daily2,3.

Curious that there are multiple parties mentioned of who can use this integration, but none of them involve individuals who volunteer to participate in research. Stay tuned for an article focused on this aspect.

DISCLAIMER

Any questions you may have about legal information within this article should be discussed with your attorney or legal counsel at your institution. SPIRIT is an educational resource ONLY and is not meant to substitute research ethics oversight or approval.

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You can also connect with me on Instagram and YouTube.

My name is Dr. Adnan Shaikh, PharmD, and I’m extremely dedicated to making significant contributions to healthcare through my comprehensive expertise in clinical pharmacy and patient care. My foundation as a Doctor of Pharmacy equips me with an in-depth understanding of pharmacotherapy, disease management, and patient-centered treatment strategies, which I actively apply in various healthcare settings to optimize medication outcomes and ensure patient safety.

Beyond my clinical practice, I have a strong commitment to advancing pharmaceutical knowledge and regulatory compliance. Specifically, my expertise encompasses the intricate requirements and guidelines set forth by major international regulatory bodies, including the Food and Drug Administration (FDA) and the European Union (EU) regulatory authorities.

Acronyms

• ANDA: Abbreviated New Drug Application

• ASMF: Active Substance Master Files

• BLA: Biologics License Application

• CDSCO: Central Drugs Standard Control Organisation

• CEP: Certificate of Suitability

• CMC: Chemistry, Manufacturing, and Controls

• CP: Centralized Procedure

• CTD: Common Technical Document

• DMF: Drug Master Files

• DCP: Decentralized Procedure

• DTC: Direct to Consume

• DHPCs: Direct Healthcare Professional Communications

• eAF: electronic Application Forms

• EC: European Commission

• EMA: European Medicines Agency

• EU: European Union

• FDA: Food and Drug Administration

• GCP: Good Clinical Practice

• ICH: International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use

• IRB: Institutional Review Board

• NDA: New Drug Application

• NP: National Procedure

• PDUFA: Prescription Drug User Fee Amendments

• PIL: Product Information Leaflet

• PIP: Pediatric Investigation Plans

• PLR: Physician Labeling Rule

• PMDA: Japan’s Pharmaceuticals and Medical Devices Agency

• PSP: Pediatric Study Plans

• QOS: Quality Overall Summary

• QRD: Quality Review of Documents

• REMS: Risk Evaluation and Mitigation Strategies

• RMP: Risk Management Plan

• SmPC: Summary of Product Characteristics

• USPI: US Prescribing Information

Should IRBs care about CTD requirements?

IRBs were established to protect the rights and welfare of human participants in research. Though IRBs aren’t engaged in regulatory pharmaceutical marketing submissions, understanding FDA and EU CTD requirements can significantly improve protocol review quality and help ensure that the proposed research generates data that is both ethical and scientifically useful. Before we further explore this, let’s understand what the CTD is and its requirements.

The CTD serves as a unified standard in the global drug approval process

In the fast-paced world of pharmaceutical development, the CTD stands as a vital bridge between innovation and patient access.

The importance of this standardized approach goes far beyond mere convenience; it fundamentally improves the quality and speed of regulatory oversight. When reviewers across different regions examine submissions in a familiar, consistent format, it enables them to perform more focused, transparent, and efficient evaluations. Companies can allocate more energy toward the actual science of drug development, ultimately benefiting both the industry and public health.

Before the CTD was introduced by the ICH, companies were forced to reformat and recompile the exact same scientific data to meet the unique, often idiosyncratic, requirements of every individual regulatory agency. This duplication of effort not only consumed massive amounts of time and financial resources but also delayed the arrival of essential medicines to patients who needed them most. Today, the CTD provides a single, harmonized structure that allows organizations to prepare one core dossier that is accepted by major regulatory authorities across the U.S., Europe, Japan, and beyond.

The CTD is structured into five modules

Each module serves a specific purpose and is dedicated to presenting specific data concerning the quality, safety, and efficacy of a medicinal product.

Module 1: Administrative and prescribing information

Module 1 is region-specific and contains administrative details such as:

• Application forms,

• Prescribing information,

• Pharmaceutical product labeling, and

• Legal regulatory documents.

The requirements of this module vary depending on the regulatory authority.

Module 2: CTD summaries

This module provides high-level summaries of the data included in subsequent modules, including:

• Quality Overall Summary (QOS),

• Nonclinical Overview and Summary, and the

• Clinical Overview and Summary.

This module is critical as it presents a concise interpretation of the detailed data, aiding reviewers in understanding the key aspects of the dossier.

Module 3: Quality

Module 3 contains detailed drug substance and product information, including:

• Drug substance characterization,

• Manufacturing process and controls,

• Specifications and analytical methods, and

• Stability data.

This module ensures that the product is consistently manufactured and controlled according to quality standards, known as CMC.

Module 4: Nonclinical study reports

Module 4 includes nonclinical (i.e., preclinical) study reports, primarily conducted in vitro and in animal models, which assess:

• Pharmacology,

• Pharmacokinetics, and

• Toxicology.

This data helps to determine the safety profile before human exposure.

Module 5: Clinical study reports

Module 5 contains clinical data generated from human trials, including:

• Clinical study reports (Phase I–IV),

• Clinical pharmacology studies, and

• Efficacy and safety data.

The CTD can be further understood from the graphic below.

Key Differences Between FDA and EU/EMA CTD Requirements

While the CTD provides a harmonized structure, there are notable differences between submissions to the FDA and the EU/EMA.

Common CTD Challenges

One of the primary challenges associated with the CTD is the complexity and volume of documentation required. The CTD is divided into five modules, each demanding extensive data related to quality, nonclinical, and clinical aspects. Preparing these modules requires significant time, expertise, and coordination across multidisciplinary teams. Smaller organizations or emerging biotech firms may struggle with resource constraints, making it difficult to compile a comprehensive and compliant submission. Additionally, maintaining consistency across all modules is a demanding task, as discrepancies can lead to regulatory queries or delays.

Another major drawback is the lack of complete global harmonization despite the standardized format. Although the CTD is accepted in regions such as the United States, Europe, and Japan, regional differences in regulatory expectations still exist. Authorities like the US FDA, EMA, and other national agencies may require additional data, specific formatting preferences, or region-specific administrative information. This results in the need for customization of submissions, thereby reducing the intended efficiency of the CTD framework.

Data standardization and integration also present significant challenges in CTD preparation. Ensuring that data from various studies, formats, and sources are aligned with CTD requirements can be difficult. Inconsistencies in data presentation, especially in clinical study reports, may lead to increased scrutiny from regulatory authorities. Moreover, the requirement for detailed summaries and overviews in Modules 2 and 5 demands high-level scientific writing skills and regulatory expertise.

Another limitation is the rigid structure of the CTD, which may not always be suitable for innovative therapies such as gene therapies, biologics, or personalized medicine. These advanced therapies often require flexible and adaptive documentation approaches that the traditional CTD structure may not fully accommodate. As a result, sponsors may need to provide additional justifications or supplementary documents, increasing the complexity of submissions.

Finally, regulatory timelines and review processes can still be lengthy despite the use of CTD. The standardized format does not necessarily guarantee faster approvals, as the review duration depends on the quality of data, regulatory workload, and the complexity of the product. Frequent updates, lifecycle management, and post-approval changes further add to the regulatory burden.

The IRB’s Role in CTD

Before a study begins, IRBs review and approve clinical trial protocols, informed consent forms, patient recruitment materials, and other participant-related documents to safeguard the rights, safety, and well-being of research participants. Their oversight helps ensure adherence to Good Clinical Practice (GCP) guidelines, ICH standards, and applicable regulatory frameworks. The ethical review and continuous monitoring provided by IRBs contribute significantly to the quality, integrity, and reliability of clinical trial data that are later included in Module 5 of the CTD for regulatory submissions. Regulatory authorities such as the U.S. FDA, EMA, and other global health agencies require evidence that clinical studies have been conducted under appropriate ethical oversight. As a result, IRB approval, ongoing review, and regulatory compliance are essential components of successful CTD submissions, marketing authorization applications, and the overall pharmaceutical drug approval process.

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DISCLAIMER

Any questions you may have about legal information within this article should be discussed with your attorney or legal counsel at your institution. SPIRIT is an educational resource ONLY and is not meant to substitute research ethics oversight or approval.

📢Top FDA Developments

Proposed Rule to Modernize Drug Manufacturing Registration

FDA issued a proposed rule that if finalized, would create a streamlined registration pathway for distributed manufacturing establishments that operate as a single establishment using a “hub-and-spoke” model. The proposed rule would also clarify registration requirements for certain foreign establishments that manufacture drugs, including active pharmaceutical ingredients, that indirectly enter the U.S. drug supply (1, 2).

Guidance on Psychedelic Drugs: Considerations for Clinical Investigations

This final guidance provides general considerations for sponsors developing psychedelic drugs for the treatment of medical conditions (e.g., psychiatric disorders, substance use disorders) and discusses recommendations for clinical investigations using psychedelic drugs. This guidance finalizes the draft guidance of the same title issued on June 26, 2023 (3, 4).

I found it curious that this guidance had no mention of Institutional Review Boards (IRBs). There was very little mention with respect to participant protections and welfare. Hopefully our SMEs in this space can provide further guidance for IRBs. Stay tuned to S.P.I.R.I.T.’s interview on US Institutional Review Board Perspectives Regarding Psychedelic Research with Jill Oliver Robinson.

FDA will host a public meeting on September 14, 2026, on potential future therapeutic use of psychedelic drugs. The agency wants to obtain feedback and perspectives on issues associated with the potential future therapeutic use of drug products containing a psychedelic drug substance in supervised and supportive settings (5).

📢Top HHS Developments

HHS and the VA entered into a Memorandum of Understanding (MOU) to strengthen collaboration on the research, clinical development, and responsible deployment to veterans suffering from serious mental health conditions of potential future rapid-acting psychedelic drug products if approved by FDA (6).

📢Top NIH Developments

Significant Website Update

In late July, NIH will start introducing a new website experience designed to make it easier to find health information, research, funding opportunities, and other resources. During the transition, you may notice changes to navigation, page layouts, and where some information is located (7).

⚡NIH Quick Hits

• HHS will accept a maximum of nine new and resubmission Phase I, Fast-track, and Direct to Phase II applications (including grants, cooperative agreements) and contract proposals from a Small Business Concern in a fiscal year (8).

• NIH leadership will host NIH’s Unified Funding Strategy on August 14, 2026 (9).

📢Other Top Developments

• NSF issued a Dear Colleague Letter prohibiting collaboration with entities on U.S. restricted parties list (10).

• DOE’s Conflict of Interest and Conflict of Commitment Policy Requirements will be effective on August 17, 2026 (11).

• ORI, in partnership with the University of Rochester, will host the next Research Integrity Officer (RIO) Boot Camp on September 2-4, 2026, in Rochester, New York (12).

• The Subcommittee on Health of the Committee on Energy and Commerce held a hearing on “Maintaining America’s Leadership in Biomedical Innovation: FDA’s Role in Advancing U.S. Drug Development” (13).

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Dr. Victoria Shepherd is the Principal Research Fellow from Cardiff University

She is also a registered nurse based in the Centre for Trials Research where I lead research to improve the inclusion of under-served populations, with a particular focus on populations and settings where informed consent can be challenging including the use of alternative models of consent.

Her research entails exploring the ethical, legal and practical issues around research involving adults who lack capacity consent and the development of complex interventions to address the barriers to inclusion.

For those hearing about ACCORD for the first time, what is the project trying to accomplish, and why is it different from previous work in this area?

We know that people living with conditions and disabilities that can affect their ability to consent to research are frequently excluded from studies that are relevant to them. For example, 1 in 3 patients with a hip fracture have cognitive impairment yet 8 out of 10 randomised controlled trials (RCTs) exclude or ignore this population, and 40% of older adults presenting to emergency departments have cognitive impairment but this population is excluded from 25% of RCTs in emergency care. There are similar patterns in research into neurological conditions, palliative care, dementia, stroke and beyond.

This exclusion is primarily due to the complex governance and practical arrangements needed to conduct research involving adults who lack capacity to consent which means it is more challenging to conduct these studies. This can lead to researchers excluding participants who are unable to provide consent, or studies that do involve them taking longer to receive the necessary approvals, can struggle to recruit, and may end up recruiting people who are more able to provide their own consent.

Previous work in the UK has focused on developing tools and resources to help researchers design and conduct studies that include adults with impaired capacity to consent, including the CONSULT programme that I lead. But we also know that there is real uncertainty about how to interpret the ethical and legal frameworks that govern research involving adults lacking capacity to consent, and that behaviour plays an important role.

ACCORD (‘Addressing Consent-based Exclusion to Improve Inclusivity in Research’) is an 8-year project funded by the Wellcome Trust which aims to understand how the ethical and legal frameworks are currently being implemented in the UK through analysing study documents, conducting interviews and focus groups, and observing research ethics committees (RECs/IRBs). We will then identify the ethico-legal issues and behavioural influences that limit inclusion, and co-design interventions in collaboration with public and professional stakeholders to target individual-level and system-wide barriers. Engaging with policymakers and a diverse range of people with lived experience and focusing on implementation will help ensure national and international impact.

Many people who lack capacity are excluded from research not because researchers don’t want to include them, but because the consent process is difficult to navigate. What motivated you to dedicate an eight-year program to addressing this issue?

Exclusion occurs partly because of the complexity of the regulation of research involving adults with impaired capacity to consent. With differing frameworks depending on the type of research, and where it is being conducted, it is no surprise that they are widely misunderstood. Unlike other areas of law, in most countries there is no case law to help interpret the complex legal provisions. Researchers, clinicians, ethics committees, and participants’ families struggle to navigate this complexity.

There is also a lack of knowledge amongst researchers and other groups about the ethical and legal frameworks, which leads to misinterpretation when applying them in practice. This further adds to the complexity that drives exclusion. Alongside this, research itself is increasingly complex, including platform trial designs and use of routine data, with implications for consent.

Given the complexity involved, a larger programme of work is needed which builds on the foundations of the previous work and takes account of the wider influences across the research system. The length of the project enables us to combine empirical research with conceptual exploration, and to develop and implement theoretically informed and evidence-based interventions to address the barriers to inclusion.

You often describe this as a problem of inclusivity rather than simply consent. Can you explain that distinction?

There is a growing recognition of the impact of a lack of inclusivity in health and care research, which leads to some groups being under-served by research. In order for the benefits of research to be distributed equitably, all populations should have the opportunity to be included in research that is relevant to them. Having unrepresentative study populations also affects the validity of a study as the results may not be generalisable to the clinical population as groups may respond differently to an intervention, and the balance of risk and benefit may not be so favourable for these groups. Consequently, improving inclusion of under-served groups in research is a priority for research funders, regulators, and policymakers.

While questions about exclusion are commonly considered with respect to sex/gender and ethnicity, this must be extended to consider other demographic factors such as disability and cognitive status where the issues encountered are even more complex. Key to ethical inclusion is finding the balance between protecting this population from unnecessary harm whilst ensuring they have equitable access to evidence-based - not evidence-biased - care.

Framing consent-based exclusion as an inclusivity issue, rather than simply a consent issue, enables us to consider the wider ethico-legal issues and systemic influences that affect the protection-inclusion balance, and also to harness the impetus for change driven by research funders, regulators, and policymakers.

Your work suggests the greatest barriers aren’t always the regulations themselves, but how they’re interpreted. What have you learned about that gap?

Whilst the regulations themselves can be problematic, we know that uncertainty about how the regulations are interpreted leads to gaps between legislation, policy and practice. This misinterpretation occurs right throughout the development, governance, and delivery of a study. This includes at the study design stage when interpreting the requirements for a study involving adults lacking capacity to consent, then navigating ethical approval processes, approaching potential participants with impaired capacity, undertaking an assessment of capacity to consent, involving an alternative decision-maker (a ‘proxy’ or ‘legal representative’), and when revisiting consent throughout the study.

This manifests in multiple ways, including incorrect use of terminology, study documents lacking essential information, being uncertain about who can act as an alternative decision-maker, miscommunicating the legal basis for their decision, and implementing unnecessary or inappropriate processes and documents. This creates what researchers have previously described as a ‘black box of horrendousness’ and contributes to the decisional and emotional burden experienced by some family members when acting as a proxy or legal representative. It directly impacts the beliefs and behaviours of researchers, practitioners, and governance organisations, leading to them ‘writing their own rules’ around inclusion. This results in different approaches being used for comparable contexts, with many adopting a more rigid approach than the law permits which limits inclusion.

Sometimes there is a real lack of consensus amongst the research community about how the regulations should actually apply, or whether they are ‘fit for purpose’. This is also something we will be considering throughout ACCORD which may lead to recommendations for policy or legislative changes.

The project involves researchers, clinicians, ethics committees, governance organizations, and families. Why was it important to include so many different perspectives?

Previous work has identified that the barriers to inclusion occur across the research system and involve different interacting actors (researchers, clinicians, ethics committees, governance organisations, and families) whose relationships are characterised by complex and dynamic interdependencies. For example, unless researchers design a study to include adults lacking capacity to consent, or an ethics committee give approval for the study to do so, those delivering the study are unable to recruit them and vice versa - even if the study is designed and approved to include adults lacking capacity to consent, unless the research team is knowledgeable and confident in approaching and recruiting them, the study will not include any participants lacking capacity. Involving these different perspectives means that the barriers can be understood and addressed across individual, organisational and system-wide levels.

IRBs are often viewed as gatekeepers, yet they also have a responsibility to facilitate ethical research. In your view, how can IRBs (or research ethics committees) move beyond simply identifying risks to actively enabling the ethical inclusion of populations that have historically been excluded from research?

As a member of an ethics committee, I understand the important role they play and that finding the right balance between protecting the rights and interests of participants and facilitating ethical research is not straightforward. I sometimes hear ethics committee members expressing frustration that a study has exclusion criteria that only allows participants who are able to provide their own consent to take part. At the same time, researchers fear what they think a REC/IRB’s reaction will be if they submit an application for a study that includes participants who lack capacity to consent. Researchers described this experience to me as sometimes being a ‘brutal’ experience or a ‘baptism of fire’. This included situations where RECs/IRBs raised concerns about the processes being proposed, although researchers considered that they had adhered to the legal frameworks to the best of their ability to interpret the requirements, which researchers viewed as gatekeeping practices.

From a behavioural perspective, we know that peoples’ decisions are influenced by the anticipation of regret and, in general, people are regret-averse which can result in risk-averse choices – in this case avoiding the ‘black box of horrendousness’ if possible! There can also be a status quo bias, where it can feel more ethically justifiable to keep things as they are, such as continuing to exclude adults lacking capacity to consent. This can affect ethics committee members (as well as researchers and others) leading to a tendency towards paternalism over proportionality.

RECs/IRBs can help to create an environment that is supportive of researchers who are attempting to navigate the complex regulations, where open communication is welcomed, and where inclusivity is viewed as a core ethical issue. RECs/IRBs can also reflect on how to find the right balance between protecting the rights and interests of participants and facilitating ethical inclusion of populations that have historically been excluded from research. This might be through considering key questions when reviewing studies, such as who is affected by the disease or condition being studied, do the aims and design of the research mean that the findings will be generalisable to these groups, how might the study processes enable or prevent these groups from taking part?

Looking beyond the UK, do you think the challenges ACCORD addresses are universal, and could the project’s findings influence international research practice?

The challenges of ethically including adults who lack capacity to consent in research are universal, although there are key contextual issues to consider such as jurisdictional and cultural differences. In ACCORD we will also be exploring the application of the findings to other international contexts. This will include exploring how the conceptual frameworks we develop align with differing ethical and legal frameworks, and whether the interventions can be adapted for other international contexts. We would welcome further international collaborators who have an interest in this area. We will also be exploring whether the methodological approach and findings can be extended to research involving other populations who are considered ‘vulnerable’ participants such as children.

When the project concludes, what impact do you hope it will have on research ethics and participant inclusion worldwide?

As a global ageing population brings rising prevalence of conditions affecting decisional capacity, unless the issues driving exclusion of adults with impaired capacity to consent from research are better understood, research will fail to meet tomorrow’s health and care needs. When ACCORD concludes, the hope is that we have created a national and international paradigm shift in understanding the barriers to the ethical inclusion of this under-served group, implemented effective interventions that help target individual-level and system-wide barriers, built research capacity in this interdisciplinary research area, and ultimately that research is better able to meet future populations’ needs.

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A few days ago, I started retro walking (i.e., walking backwards) on purpose, as a form of exercise. This activity is popular in physical therapy and sports training because it recruits muscles and balance systems that you wouldn’t otherwise use.

It’s a lot harder than it looks.

This is something I used to do before I started my workday. I’ve also heard wonders on what this can for joint health and knee relief. There are also cognitive benefits such as improved focus, coordination, and overall brain-body connection.

What I didn’t expect was how directly it would map to my passion.

The parallels kept showing up faster than I could ignore them, so naturally I decided to write about it.

Momentum is the enemy of attention

Forward walking is automatic. Your body has done it so many times that conscious thought barely enters the process. You can walk and think about something else entirely, and your feet will still find the ground and keep momentum.

Retro walking will not let you do that.

The moment your attention drifts, your balance goes with it. Every step requires a decision. There is no coasting.

This is precisely the failure mode that shows up in mature compliance programs. Momentum builds what I call “institutional autopilot.” For example, a protocol gets approved the same way it was approved last year, because it looks the same as last year’s protocol.

The discipline of retro walking is the discipline of staying present with each step instead of trusting that the last hundred steps guarantee the next one. I find extreme value in tools such as the IRB Precedent Tool, especially for those real oddball scenarios. However, just like with anything in life, it’s important to stay present and not make assumptions because something “looks the same”.

Slowness is not the same as inefficiency

There is a real temptation, in retro walking and in regulatory review, to speed up.

In walking, that temptation ends in a stumble almost immediately. The body punishes it right away. Compliance systems rarely get that immediate feedback. A rushed review, a corner cut, a training module clicked through without engagement, none of these produce a stumble you can see in the moment.

We’ve all heard the unfortunate conversation and perception of IRB review as a bottleneck. Speed is treated as the value and thoroughness as the tax. Retro walking reframes that instinct in a way I find useful.

The pace of review isn’t the obstacle. It’s the mechanism that keeps you from falling.

You can’t see where you’re going, so you have to coordinate

The hardest part of walking backwards is the obvious one: you can’t see your destination.

Your eyes, normally the dominant sense for navigation, are no longer reliable for the direction of travel. Your body compensates by leaning harder on proprioception, peripheral vision, and the memory of the space behind you. No single sense can do the job alone.

No single component of the research protection system (e.g., the IRB, the investigator, the compliance office, etc.) has a clear forward view of every risk. Each one sees a different part of the picture, and each one is limited in a different way.

• The IRB sees protocol design and consent but not day to day conduct.

• The investigator sees day to day conduct but may be too close to the work to see design flaws.

• The compliance office sees patterns across studies but not the texture of any single one.

Oversight fails when one of these components tries to walk the whole path relying only on its own view. The way a person might try to power through retro walking using only their eyes and ignoring everything else their body is telling them. It works when the systems function as a coordinated whole, each contributing the kind of awareness the others cannot supply for themselves.

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Any questions you may have about legal information within this article should be discussed with your attorney or legal counsel at your institution. SPIRIT is an educational resource ONLY and is not meant to substitute research ethics oversight or approval.

📢Top FDA Developments

Correction to RFI on Expedited IND Pilot Program

FDA is correcting the email address for this public comment request (1).

⚡FDA Quick Hits

• Approved allogeneic T-cell-based immunotherapy reduces chronic graft-versus-host disease (GVHD) in patients with blood cancers undergoing stem cell transplantation (2).

• Approved gene therapy provides new treatment option for children 2 years and older with life-threatening blood disorder (3).

📢Top HHS Developments

2026 Unified Agenda

Over the holiday weekend, HHS issued the 2026 Unified Agenda with notable significant rule changes in healthcare, research compliance, and regulatory affairs (4). This will be analyzed in detail for the monthly Federal and Congressional Scoop.

⚡HHS Quick Hits

• OHRP is seeking public comment on revising the agency’s research complaint form (5).

📢Top NIH Developments

Federal Demonstration Partnership (FDP) Phase VIII Notice

This notice announces a solicitation for large and small public and private colleges and universities (including predominantly undergraduate institutions, minority serving institutions, and emerging research institutions), non-profit research and education organizations, and research hospitals and medical centers that are recipients of federal research or research-related funding to participate in Phase VIII of the Federal Demonstration Partnership (FDP) (6).

⚡NIH Quick Hits

• In intramural news:

  • NIH issued the most expansive data release in the history of its All of Us Research Program, making available data from more than 747,000 participants and establishing All of Us as the world’s largest integrated genomic and electronic health record (EHR) database (7).

  • NIH researchers showed that elevated levels of certain circular RNAs in the blood nearly tripled patients’ risk of developing symptoms, suggesting these molecules are more sensitive to symptom onset than traditional Alzheimer’s disease biomarkers (8).

• In extramural news:

  • NIH published a resource detailing key study information required for ClinicalTrials.gov records (9).

  • NIH contract opportunities are showcased on SAM.gov and are different from receiving an NIH grant (10).

  • NIH announced a new parent funding opportunity designed to help promising Ph.D. students (11).

📢Other Top Developments

Senate Committee on Appropriations and OMB’s Proposed Rule

The Committee sent a letter to the OMB to extend the comment period by at least 90 days and withdraw portions of the rule that would potentially harm small and rural communities and scientific and biomedical research (12). Further, this Committee along with Senate and House Appropriations Subcommittee on Energy and Water Development also sent a letter to OMB with respect to the Department of Energy (DOE). They stressed how this would enable political appointees to terminate grants for virtually any reason they please, which will put critical energy projects on the chopping block and scare private investment away from projects that lower Americans’ costs (13).

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A Question Older Than It Looks

In 1982, a group of researchers studying informed consent did something simple. They asked people who just agreed to join a clinical trial to explain, in their own words, what would happen to them next.

One woman, 25 years old, with three years of college, understood the study better than almost anyone else they interviewed. She could describe all three treatment groups, including the placebo group. She knew assignment would be random. She knew dosages would be adjusted based on blood tests.

Then the researchers asked her directly how her own medication would be chosen.

She said she had no idea.

She then added, “I hope it isn’t by chance.”

Pressed further, she gave a definition of “random” that was completely correct: one person gets one thing, the next gets another. Like a lottery.

She had just explained the exact mechanism that would decide her treatment.

Then, as she described herself, she reached for a different word than the one chosen by the interviewers. Nobody told her to use it. It’s simply the word most people reach for when picturing someone getting medical care.

That question, patient or subject, might sound like a technicality. It isn’t.

In 2025, the organization that sets the global standard for how clinical trials are run made a deliberate change. It retired the word “subject” and replaced it everywhere with “trial participant.” This wasn’t a copyedit. It was an acknowledgment, decades overdue, that the old word wasn’t doing its job.

A federal letter issued in 2026 still can’t hold one term steady across a single page.

The people who wrote the foundational rules on this question, back in 1977, weren’t sure either. Two transcripts I obtained directly from Georgetown University, scanned at my request by the Archivist for the Kennedy Institute of Ethics, catches them arguing about it live.

The Line Belmont Drew

In 1979, a federal commission published what would become the founding document of American research ethics: the Belmont Report. Its first job was to draw a line between two things that can look identical from the outside.

• “Practice” is what a doctor does when the whole point is to help the specific person in front of them.

• “Research” is something else: an activity designed to test a question and produce knowledge that will help future patients, whether or not it helps the person enrolled today.

That distinction is the reason hospitals have ethics review boards at all. Belmont presents it as settled, confident guidance. It wasn’t drawn as cleanly as it reads.

Two Unresolved Boundaries, Caught Live

About two years before Belmont was finished, the commission writing it was still fighting two overlapping battles at once:

• What actually counts as research in the first place, and

• What to even call the person involved in the research project.

The transcripts of those meetings aren’t online. I obtained them from Georgetown University’s Kennedy Institute of Ethics archive, scanned at my request by the Archivist for the Kennedy Institute of Ethics.

At the August 1977 meeting, one member pushed to draw a clean line between “research” and something he called a demonstration project: a school trying a new teaching method, say, just to see if it helped.

The chairman asked for a clear example that wasn’t research.

A staff member finally cut through the debate: these kinds of activities, he said, will just vary. There’s no clean rule. That exchange becomes, almost word for word, Belmont’s own section on the boundary between practice and research.

In the room, it was still unresolved.

Later that same meeting, the bioethicist Robert Levine objected to the Commission inventing a new, technical meaning for an ordinary word.

He said plainly that he was fighting a rear-guard action in defense of the English language. “Subject” already had a perfectly good dictionary definition, he argued; the Commission didn’t need a new one just to tell review boards what to look at. Others pushed back; the point wasn’t literary purity. It was giving oversight boards the right scope. Levine himself later admitted his own proposed definition was incomplete. The people about to hand the English-speaking world its regulatory word for “the person in a study” weren’t convinced, in that room, that it was the right word at all.

A month later, the uncertainty hadn’t gone away, it had just gotten quieter.

One commissioner asked whether the definition of “human subject” actually resolved when informed consent was required. Another said plainly: no, that’s still unresolved.

In a separate exchange, a member describing his own approach to consent, a mutual, signed agreement rather than a one-sided form, called the people in his studies participants. It’s one of only two times that word comes up across two full days of transcripts.

It didn’t catch on. It would take nearly fifty years for the field to circle back and settle on it.

When Lines Blur in Practice

The instability wasn’t only about which word to write down. It showed up in what people believed about their own care. Decades of research, building on that original 1982 study, found something consistent: people can understand a study’s mechanics perfectly and still can’t quite believe those mechanics apply to them. They assume, reasonably, that the person treating them is choosing what’s best for them, the way ordinary medicine works. Often, in a trial, no one is making that choice at all.

Its authors call the people in their studies “subjects” most of the time. Partway through, describing the same people, they switch to “patients.” At another point they reach for a term that doesn’t officially exist: “patient-subjects.”

A Letter from May 2026 and What It Actually Shows

In May 2026, the federal Office for Human Research Protections (OHRP) closed an investigation into the Medical College of Wisconsin. The complaint, filed the previous October, alleged that clinical staff told patients a trial was their only option, withheld standard treatments while a trial slot opened up, and in some cases stopped caring for patients who declined to enroll. Both OHRP and the institution’s own internal investigation found the allegations unsubstantiated. Nothing here was proven.

• In one instance, OHRP’s letter uses “subject” five times, always when citing the actual regulation.

• It uses “patient” five times, always when describing the alleged conduct.

• It uses “participant” once, in the closing line.

Three different words, one letter, for the same group of people. (The letter also notes its review wasn’t comprehensive of the institution’s broader oversight procedures: language that, as it turns out, appears almost verbatim in a 2024 letter to an unrelated institution. It’s evidently standard OHRP boilerplate, not a choice made about this case specifically.)

I reviewed 25 federal determination letters issued between 2020 and 2026 (post-Common Rule era - I’ll explain this what the Common Rule is shortly). The word “subject” appears roughly 300 times, “participant” about 37, and “patient” only 18. The clearest example of the pattern isn’t the 2026 case at all.

It’s a 2023 letter about UCLA, where a research participant was injured during a study.

• Every regulatory citation in that letter uses “subject.”

• Every sentence describing what actually happened to the injured person uses “participant”, sixteen times more often than “subject” appears at all.

The federal office writing these letters, again and again, over years, cannot hold one word steady for the person the letter is actually about. This was never really a story about one hospital. It’s a story about a pattern that runs through the whole archive.

The Rule That Didn’t Get the Memo

Last year, the clinical trials industry’s own rulebook stopped calling people in studies “subjects.” Even the FDA agreed: in September 2025, it published its own guidance saying “participant” is the right word.

But guidance isn’t a rule.

It doesn’t change the actual regulation, the Common Rule, that the federal research protections office enforces day to day. That rule still says “subject.”

This isn’t the United States lagging the rest of the world. It’s one part of the federal government agreeing, in writing, that the word needs to change, while the rule in another part of that same government still enforces never got the memo.

Fifty Years On

This was never really a story about one hospital, or one federal office’s habits.

The next time someone sits across from a doctor who is also, in that moment, a researcher, the word used to describe them won’t be neutral. It will shape what they’re told, what they believe their options are, what protections they think apply to them.

The woman in 1982 who called herself a patient in the same breath she correctly explained randomization never got a clear answer to which she actually was.

Fifty years later, the people who write the rules still haven’t given one.

Neither, it turns out, has anyone else.

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📢Top FDA Developments

Master Protocols for Drug and Biological Development Draft Guidance

The draft document provides recommendations on the design and analysis of trials conducted under a master protocol as well as guidance on the submission of documentation to support regulatory review (1, 2). This will revise and replace the previous draft guidance for industry of the same name issued on December 22, 2023. The most notable change is the addition of recommendations on basket trials (3).

FDA recommends a central institutional review board (IRB) review the master protocol, informed consent, and other relevant documents for trial monitoring.

Could this mean that the single (central) IRB mandate is soon to be finalized?

The final rule still holds a deregulatory status within the Unified Agenda (5).

DOJ and FDA Join Forces Falsifying Clinical Trials Data

A doctor and two staff members of a medical research center were charged with their alleged scheme to falsify data in clinical trials of prospective new drug treatments. A third staff member was also charged in a criminal information. The defendants allegedly fabricated testing data and falsified other records while conducting clinical trials sponsored by a pharmaceutical development company. The trials were designed to test prospective new drugs to evaluate their safety and efficacy for potential approval by the FDA.

Further, the defendants allegedly used identification documents from people, who did not actually participate in trials, to create false records purporting to show those individuals participated and generated test results. The indictment also alleges that the scheme caused the falsified test data to be submitted into the clinical trial database systems used for evaluating prospective new drugs (6).

RFI on Expedited IND Pilot Program

The FDA is requesting public comment on the Expedited Investigational New Drug (IND) pilot program; to shorten the time it takes from drug identification to first-in-human (FIH) study, while protecting clinical trial participants (7).

Specifically, the pilot aims to:

• Test whether they can improve the quality of IND submissions such that there are fewer instances where it is necessary to impose phase 1 clinical holds;

• Reduce FDA review time through a rolling submission process; and

• Test whether clinical trial initiation activities, such as IRB review and site contracting, can be conducted in parallel with IND development and review, thereby accelerating the time from when FDA permits a clinical investigation to begin to FIH study initiation.

📢Top HHS Developments

Operation TrialBlazer: A Path Forward for Clinical Research?

HHS launched a multi-agency effort, Operation TrialBlazer, to strengthen America’s leadership in clinical research, accelerate the development of lifesaving treatments, and ensure that patients have access to the most innovative therapies in the world. (8).

Under this initiative:

• FDA is proposing measures to accelerate drug development by shortening early clinical trial timelines, clarifying regulatory expectations, and supporting approval based on one high-quality pivotal trial with confirmatory evidence when appropriate (see RFI on Expedited IND Pilot Program).

• NIH is promoting faster, more efficient clinical research by supporting well-designed trials and advancing the responsible use of AI, real-world data, human cell-based models, and other innovative research tools.

  • NCATS is leveraging advances in personalized CRISPR-based gene editing to accelerate the development of new therapies for patients with rare diseases.

  • NCI is streamlining cancer clinical trial activation and improving participant enrollment to accelerate the development of new cancer treatments.

• ONC is exploring ways to use electronic health records to better connect eligible patients with clinical trial opportunities during routine healthcare.

• ARPA-H is modernizing clinical research through innovative trial designs and AI-enabled technologies that improve safety prediction, dose optimization, and trial efficiency.

• HHS OIG is seeking public input on potential updates to federal anti-kickback safe harbor and beneficiary inducement regulations related to participation in clinical trials (see RFI on Federal Anti-Kickback Statute and Clinical Trial Renumeration).

Doesn’t this make you wonder about OHRP?

TrialBlazer highlights that expanding clinical trial access can’t be done alone by the FDA, but in effort with other agencies (including OHRP) to identify and dismantle the financial and logistical barriers that disincentivize patients and clinicians from participating in clinical trials.

The plan further describes balancing participant protections but doesn’t necessarily state or provide examples on how this would be managed.

RFI on Federal Anti-Kickback Statute and Clinical Trial Renumeration

The Office of Inspector General (OIG) issued an RFI on whether any additions or modifications are needed to the safe harbor regulations under the Federal anti-kickback statute or the exceptions to the civil monetary penalty provision prohibiting inducements to beneficiaries (the “Beneficiary Inducements CMP”) for remuneration provided to individuals in connection with their participation in clinical trials (9).

📢Top NIH Developments

New Office of Research Innovation, Validation, and Application (ORIVA)

ORIVA will advance the use of human-based research technologies across NIH. ORIVA will coordinate NIH-wide efforts to develop, validate and scale New Approach Methodologies, or NAMs, including 3D human tissue models, computational tools and other animal-free methods that can better reflect human biology. The office will also serve as a hub for interagency coordination and regulatory translation (10).

RFI to Limit the Number of Submissions Made by a Single Investigator

NIH’s interest in limiting submissions stems from several studies suggesting that scientific output doesn’t increase proportionally as funding accumulates in a single laboratory. Research also suggests that smaller teams may be more likely to produce disruptive or innovative findings. Finally, large and complex research enterprises can present challenges for oversight, mentoring, and project management.

NIH wants to specifically hear public comments related to:

• Pros and/or cons of the policy,

• The optimal number of Research Project Grants (RPGs) for the cap (e.g., two, three, or four),

• Strengths and weaknesses of the proposed implementation strategies, and

• Possible unintended consequences or policy loopholes (11, 12).

  ---

RFI on Measuring and Awarding Scientific Impact

NIH seeks public input on the defining features of modern 21st-century science that should be measured, recognized, and incentivized. These features can include:

• Rigor and reproducibility,

• Data, software, and model sharing,

• Training and mentorship,

• Collaboration,

• Entrepreneurship and translation,

• Foundational scientific exploration, and

• Public impact (13, 14).

📢Top NSF Developments

Guidance on Financial Assistance (GFA)

NSF issued an information collection request entitled “U.S. National Science Foundation Proposal/Award Information—NSF Guidance on Financial Assistance” to seek approval to extend with revision an information collection for three years (15).

Compared with the current PAPPG, the proposed GFA represents a substantial policy modernization. The most consequential changes include:

• A comprehensive research security framework with expanded disclosures and institutional certifications;

• Broader Responsible Conduct of Research (RCR) training requirements integrating research security and export controls;

• New foreign financial disclosure and former NSF employee disclosure obligations;

  implementation of recent Executive Orders (EO) affecting biological research, scientific integrity, public access, and grant administration;

• Adoption of proposed OMB Uniform Guidance revisions, including a 15% de minimis indirect cost rate and the proposed disallowance of publication costs; and

• Structural reorganization into 26 topical guides intended to make NSF policies easier to navigate while distinguishing policy requirements from implementation procedures (16).

Comparison between PAPPG and GFA was completed via ChatGPT and Microsoft Copilot, then reviewed by the author.

📢Top White House Developments

EO an Advancing AI Innovation and Security

President Trump signed an EO to advance AI innovation to strengthen America’s cybersecurity, protect critical infrastructure, and ensure the United States remains the global leader in AI innovation. The EO directs appropriate agencies to prioritize the cyber defense of National Security Systems, Department of War information systems, and civilian Federal government information systems (17, 18).

NSPM-11: AI in the National Security Enterprise

National Security Presidential Memorandum 11 (NSPM-11) will responsibly accelerate the use of AI across intelligence and warfighting domains in line with American values. The Trump Administration will accelerate the development and use of AI for national security applications, guided by the following four pillars:

• Adoption,

• Adaptation,

• Assurance, and

• Accountability (19).

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The Next Frontier of Quantum Innovation

The EO establishes a national effort to develop the first ever quantum computer powerful enough to initiate the era of quantum-enabled scientific discovery and accelerate quantum capabilities for commercial applications (20, 21). This includes evaluations of quantum computing system capabilities, an assessment of the resources necessary to build this science-enabling quantum computer, and development of specifications for such a system.

Multiple agencies will be engaged in updating the National Quantum Strategy, including NSF, to support the maturing Quantum Information Science and Technology (QIST) ecosystem, including promoting commercialization and deployment of QIST, supporting the quantum-enabling technology ecosystem, and encouraging partnerships with United States industry. NSF issued a statement regarding the EO and the agency’s commitment to securing American leadership in quantum information science and technology (22).

📢Top Congressional Developments

Senate HELP Committee on Largest Public Health System’s Recent Cybersecurity Breach

The U.S. Senate Health, Education, Labor, and Pensions (HELP) Committee pressed on the recent cybersecurity incident affecting NYC Health + Hospitals, the largest public health system in the U.S. Over a three-month period, NYC Health + Hospitals allowed hostile actors access to over one million patients’ health insurance information, medical information, biometric information, precise geolocation data, and Social Security numbers. Earlier this Congress, the HELP Committee passed Cassidy’s Health Care Cybersecurity and Resilience Act to safeguard Americans’ health data. The Committee wrote a letter to the CEO of the NYC Health + Hospitals about the incident (23).

House Committee on Science, Space, and Technology Pushes for Public Hearing on Jim O’Neill as the Next NSF Director

The House sent the Senate HELP Committee a letter urging him to hold a public hearing on the nomination of Jim O’Neill for Director of the NSF (24). Ranking House Member calls into question whether O’Neill is qualified for the role and implores the Senate to examine O’Neill’s involvement in a controversial grant awarded to an unqualified research group to study vaccine efficacy on infants in Guinea-Bissau during his time as leader of the CDC.

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In May 2025, the Administration issued EO 14303, Restoring Gold Standard Science. The EO laid out a vision for federal science built around reproducibility, transparency, uncertainty, collaboration, falsifiability, unbiased peer review, acceptance of negative results, and freedom from conflicts of interest. It was an ambitious statement leading to even more difficult questions for its implementation.

• What does “Gold Standard Science” look like when it moves from a presidential directive into the machinery of federal research policy?

• How does it shape grantmaking?

• How does it affect the way agencies evaluate success?

• How does it change incentives for researchers and institutions?

The first is the Office of Management and Budget’s (OMB) proposed overhaul of federal grant administration. OMB’s proposal emphasizes accountability, transparency, oversight, research security, stewardship of taxpayer funds, and alignment with federal priorities. The second is NIH’s Request for Information on Measuring and Rewarding Scientific Impact. NIH asks a different kind of question: what should the biomedical research enterprise actually measure, recognize, and incentivize?

Together, these documents unveil three layers of the Administration’s science policy:

• The Gold Standard Science EO sets the principles.

• NIH’s RFI explores incentives.

• OMB’s proposed rule builds the oversight framework.

The question is whether those layers reinforce one another or whether they compete against one another about how to truly strengthen American science.

Gold Standard Science as a Statement of Values

The Gold Standard Science EO frames itself around public trust.

It begins from the premise that confidence in science has declined and that federal agencies have a responsibility to restore credibility in how scientific information is produced, interpreted, communicated, and used in decision-making.

The EO defines Gold Standard Science as science that is:

• Reproducible,

• Transparent,

• Communicative of error and uncertainty,

• Collaborative and interdisciplinary,

• Skeptical of its findings and assumptions,

• Structured for falsifiability,

• Subject to unbiased peer review,

• Accepting of negative results, and

• Without conflicts of interest.

Those principles are familiar to anyone who follows scientific integrity, open science, or reproducibility debates. They reflect concerns that have been building for years: irreproducible findings, publication bias, weak incentives for replication, conflicts of interest, selective communication of uncertainty, and overreliance on prestige-based measures of scientific success. The order’s most interesting feature is that it connects scientific quality to governance.

Gold Standard Science is not merely about how researchers conduct experiments. It’s about how agencies use scientific information, communicate uncertainty, disclose assumptions, and make decisions that affect the public. That makes the EO more than a scientific integrity document. It is also a science policy document. However, principles alone don’t change scientific culture. Incentives might.

NIH asks the incentive question

That is why NIH’s RFI on Measuring and Rewarding Scientific Impact is so important.

NIH begins from a premise that closely tracks the Gold Standard Science framework: modern biomedical research is collaborative, interdisciplinary, dependent on transparent reporting, strengthened by replication, and improved through careful interpretation of methods and analyses. Then, NIH issues an RFI not only highlighting these principles, but how incentives can aid in the shift if science culture.

The agency asks what features of modern science should be measured, recognized, and rewarded. It specifically invites comment on:

• Rigor and reproducibility,

• Data, software, and model sharing,

• Training and mentorship,

• Collaboration,

• Entrepreneurship and translation,

• Foundational scientific exploration, and

• Public impact.

This is a different approach from the OMB. NIH is not primarily asking how to monitor scientists. It is asking how to reward better science. Scientific culture is shaped by what institutions value. For decades, academic success has often been measured through publications, citation counts, and journal prestige (1). Though these metrics can be meaningful, it doesn’t paint the complete picture.

• What about replication?

• What about careful data curation?

• What about mentorship and team science?

NIH’s RFI implicitly recognizes that if federal science policy wants reproducibility, transparency, and public impact, then federal research systems must reward those behaviors.

OMB asks the oversight question

OMB’s proposed grant reform approaches the same problem from a different direction.

Where NIH asks what should be rewarded, OMB asks what should be controlled. The proposal emphasizes transparency, accountability, oversight, and stewardship of taxpayer resources. It reflects concern that federal financial assistance has not always been sufficiently aligned with law, executive branch policy, agency priorities, national interests, or public accountability.

OMB’s proposal includes expanded risk reviews, additional disclosures, enhanced oversight of recipients and subrecipients, increased scrutiny of foreign affiliations and collaborations, and clearer agency authority over awards. From OMB’s perspective, these reforms strengthen integrity in federal funding.

Publicly funded science depends on public trust. Taxpayer dollars should be managed responsibly. Conflicts of interest matter. Research security matters. Transparency matters. Federal agencies have legitimate obligations to ensure that awards are used for authorized purposes and that recipients comply with applicable requirements.

In that sense, OMB’s proposal shares some DNA with Gold Standard Science:

• Both are concerned with trust.

• Both are concerned with transparency.

• Both are concerned with credibility.

• Both seek to prevent misuse of scientific or public authority.

Both questions are legitimate. They may not always point in the same direction.

Transparency: One Area of Alignment

Transparency is the clearest overlap among the three documents.

Gold Standard Science calls for transparency in data, assumptions, analyses, uncertainty, and communication. NIH asks how to reward data, software, and model sharing. OMB seeks more transparency in federal awards, recipient conduct, subrecipient reporting, and institutional accountability.

For scientists, transparency often means open data, clear methods, reproducible analyses, disclosure of limitations, and willingness to share tools so others can validate results (2).

• For NIH, transparency becomes an incentive problem: how should the system recognize researchers who build reusable datasets, develop software, share models, or make replication possible?

• For OMB, transparency becomes an accountability problem: how should agencies know who receives federal funds, how those funds are used, and whether recipients are complying with federal requirements?

These are related but not identical. One form of transparency improves science. Another improves grant administration. The strongest federal policy would connect the two.

The risk is that administrative transparency can expand without necessarily improving scientific transparency. More reporting is not the same as more reproducibility (3). More disclosure isn’t the same as better methods. More oversight doesn’t equal better science. This is the distinction policymakers must bear in mind.

Reproducibility: Incentives May Matter More than Oversight

Gold Standard Science places reproducibility near the center of federal science policy. NIH’s RFI does the same.

The agency’s Replication and Reproducibility Initiative and its RFI suggest that NIH understands reproducibility as a cultural and structural challenge. Researchers need incentives, infrastructure, and recognition for replication and reproducibility work.

OMB’s proposal is less directly connected to reproducibility. Its oversight mechanisms may improve compliance, but compliance is not the same as reproducibility. A study can comply with federal grant requirements and still be difficult to reproduce. A project can satisfy reporting obligations while still failing to share data, methods, code, or models in a useful way. This is where NIH’s approach appears more closely tailored to Gold Standard Science than OMB’s proposed rule.

Reproducibility isn’t achieved by adding more administrative review. It’s achieved by changing scientific incentives, improving infrastructure, supporting replication, rewarding transparency, and recognizing work that makes science more reliable. OMB can support that goal indirectly by ensuring accountability and stewardship. However, NIH’s RFI gets closer to the heart of the scientific problem.

Peer Review: A Major Tension

Gold Standard Science explicitly includes unbiased peer review.

NIH’s RFI reflects an interest in rethinking how scientific contributions are evaluated, especially in a research environment where team science, data sharing, mentorship, translation, and public impact may not be adequately captured by traditional metrics. OMB takes a different position. It emphasizes that peer review is advisory and that agencies retain authority to make final funding decisions based on law, policy, priorities, risk, and national interest. Federal agencies have always considered factors beyond scientific merit. Congress sets statutory purposes. Administrations set priorities. Agencies have responsibilities that extend beyond technical evaluation.

If Gold Standard Science depends on unbiased peer review, then the role of peer review in grantmaking matters. If peer review becomes too weak, scientific quality may suffer. If agency discretion becomes too broad, researchers may worry that scientific merit is being subordinated to political or administrative priorities. The question isn’t whether peer review or agency discretion should prevail. The question is how to define the boundary between them.

The Value Public Impact

NIH’s RFI adds something important to the Gold Standard Science conversation: public impact.

The agency asks how to recognize broader contributions to health outcomes, economic growth, clinical practice, public trust, accessibility, and societal benefit. This is significant because it moves beyond narrow productivity metrics.

• A dataset that supports future discoveries has impact.

• A replication study that prevents wasted investment has impact.

• A mentoring environment that trains the next generation of scientists has impact.

• A communication effort that strengthens public trust has impact.

OMB is also concerned with public value, but primarily through the language of stewardship and taxpayer accountability. NIH’s RFI is concerned with public value through scientific contribution. Those approaches are complementary, but they emphasize different dimensions of the same problem. OMB asks whether public funds are being used appropriately. NIH asks whether scientific work is being valued appropriately. Gold Standard Science needs both.

The missing bridge: administrative burden

One issue connecting all three documents but remains unresolved is the administrative burden of implementing these policies.

Gold Standard Science requires more transparency, more documentation of uncertainty, more attention to reproducibility, and more scrutiny of conflicts of interest. NIH wants better incentives for rigorous, collaborative, and mission-driven science. OMB wants stronger oversight and accountability. Each goal is defensible.

Researchers already operate in a dense regulatory environment. Universities manage overlapping requirements related to grants, human research, animal care, biosafety, conflicts of interest, export controls, and research security. Adding new expectations without removing obsolete or duplicative ones can make the system heavier.

The research community’s responses to OSTP’s RFI repeatedly emphasized this point. Stakeholders did not ask for the elimination of oversight. They asked for smarter oversight. That distinction should guide implementation of Gold Standard Science. If Gold Standard Science becomes another compliance layer, it may undermine the acceleration agenda. If it becomes a framework for aligning incentives, improving transparency, supporting reproducibility, and reducing low-value burden, it could strengthen American science. NIH’s RFI points toward the second path. OMB’s proposed rule risks being read as the first.

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📢Top FDA Developments

FDA Launches Initiatives with Global Regulatory Counterparts

First, the FDA launched a reciprocal staff-sharing initiative with its regulatory counterpart in the United Kingdom, the Medicines and Healthcare products Regulatory Agency (MHRA) (1). Having embedded staff in place will deepen this relationship and is expected to accelerate joint initiatives, enhance policy development, and help to identify strategic opportunities in such key areas as medical devices, artificial intelligence, rare diseases, and real-world evidence/real-world data.

FDA also signed a landmark Statement of Cooperation (SOC) establishing a formal framework for regulatory collaboration with the African Medicines Agency (AMA) (2). This SOC advances regulatory convergence, harmonization, and information exchange with the following focus areas:

• Reliance-based regulatory pathways,

• Clinical trial oversight for innovative medical products,

• Emergency regulatory response,

• Quality management systems,

• Digital transformation, and

• Combating substandard and falsified medical products.

⚡FDA Quick Hits

• Two guidance documents were distributed (3, 4, 5) and two medical device rules were published (6, 7).

• FDA broadened access to opioid overdose spray (8).

• FDA approved:

  • Over the counter (OTC) Glucose monitor for children (9).

  • Indication for certain pediatric patients with recently diagnosed Stage 3 Type 1 Diabetes (10).

📢Top NIH Developments

NIH’s New Office: Office of Research Innovation, Validation, and Application (ORIVA)

ORIVA will advance the use of human-based research technologies across NIH. ORIVA will coordinate NIH-wide efforts to develop, validate and scale New Approach Methodologies, or NAMs, including 3D human tissue models, computational tools and other animal-free methods that can better reflect human biology. The office will also serve as a hub for interagency coordination and regulatory translation (11).

Two Request for Information (RFIs) of Note

NIH seeks public input on the defining features of modern 21st-century science that should be measured, recognized, and incentivized. These features can include:

• Rigor and reproducibility,

• Data, software, and model sharing,

• Training and mentorship,

• Collaboration,

• Entrepreneurship and translation,

• Foundational scientific exploration, and

• Public impact (12).

NIH’s National Library of Medicine (NLM) invites input from the biomedical, public health, informatics, publishing, and history of medicine communities to inform the future direction of the Grants for Scholarly Works in Biomedicine and Health program. This RFI seeks feedback on program priorities, scope, structure, and opportunities to enhance the relevance, impact, and dissemination of scholarly works in an evolving digital and data-driven environment (13).

⚡NIH Quick Hits

• In intramural news:

  • Dr. Raymond Jacobson selected as director of the NIH Center for Scientific Review (14, 15).

  • Researchers discover single-cell brain activity that underlies human speech (16).

  • For adults with prediabetes, lifestyle intervention lowered risk of developing multiple chronic conditions (17).

• For extramural news:

  • Article shared on defining a “Person Month” and its calculation (18).

📢Other Top Developments

Update from the National Science Foundation (NSF) on OOI

NSF has ceased all plans on dismantling the Ocean Observatories Initiative (OOI). Though the Endurance Array has been removed from the water, NSF will redeploy the equipment after servicing (19).

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I’m so excited to share the launch of my first FREE course designed for:

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By the end of the course, you’ll be able to:

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You can enroll today: Why Applied Research Ethics Matters in Human Subjects Research.

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📢Top FDA Developments

FDA’s Approach to Generic Drug Oversight

The FDA updated multiple product specific guidance documents to reduce expensive and time-consuming clinical studies needed for generic inhalation products, which could help bring more affordable options to patients sooner. FDA continues to prioritize the speed and efficiency with which generic drugs are regulated, while balancing the need for minimizing risk and ensuring access to quality medications.

The Quality Management Maturity Program aims to foster quality culture, encourage strong quality management practices, identify improvement opportunities, and ensure reliable product supply (1).

RFI Comment Extension on Repurposing Drugs for Unmet Needs

The Request for Information (RFI) originally issued on May 12, 2026, has extended its public comment period until July 13, 2026. In this RFI, the FDA requested comments to solicit input on FDA's efforts with respect to drug repurposing to address unmet medical needs (2).

Reopening RFI on Recommendations on Scale-Up and Postapproval Changes Guidance for Industry

The RFI originally issued on March 3, 2026, has reopened its public comment period until July 13, 2026. In this RFI, the FDA requested comments on the Agency's series of guidance documents for industry on scale-up and postapproval changes for specific dosage forms (3).

⚡FDA Quick Hits

• Six rules published related to medical devices (4, 5, 6, 7, 8, 9).

📢Top NIH Developments

RFI to Limit the Number of Submissions Made by a Single Investigator

NIH’s interest in limiting submissions stems from several studies suggesting that scientific output doesn’t increase proportionally as funding accumulates in a single laboratory. Research also suggests that smaller teams may be more likely to produce disruptive or innovative findings. Finally, large and complex research enterprises can present challenges for oversight, mentoring, and project management.

NIH wants to specifically hear public comments related to:

• Pros and/or cons of the policy,

• The optimal number of Research Project Grants (RPGs) for the cap (e.g., two, three, or four),

• Strengths and weaknesses of the proposed implementation strategies, and

• Possible unintended consequences or policy loopholes (10, 11).

⚡NIH Quick Hits

• For extra,ural news:

  • Article defining the differences between NIH institutes, centers, and office’s highlighted topics and general interest areas (12).

  • Bookmark NIH’s Grants and Funding outreach calendar (13).

• For intramural news:

  • NIH Selects Dr. Steven Schiff as Director of Fogarty International Center, Associate Director for International Research (14).

  • NIH research establishes new framework for the role of senescence in aging (15).

  • NIH researchers trigger sleep’s restorative effect in parts of the awake brain (16).

  • NIH researchers identify regulatory cells that shield against inflammatory bowel disease (17).

📢Top HHS Developments

HHS defined public health in a joint statement to ensure that decisions affecting U.S. workers, families, farmers, and businesses are guided by transparent, evidence-based processes that reflect America’s interests and scientific standards. Interestingly, the Trump Administration is committed to improving the health and safety of the American people, including rigorous, independent scientific expertise (18).

⚡HHS Quick Hits

• HHS announce a historic development to increase nutrition requirements at every level of U.S. medical education, competency-evaluation, training, and residency (19).

📢Other Top Developments

NSPM-11: Artificial Intelligence (AI) in the National Security Enterprise

National Security Presidential Memorandum 11 (NSPM-11) will responsibly accelerate the use of AI across intelligence and warfighting domains in line with American values. The Trump Administration will accelerate the development and use of AI for national security applications, guided by the following four pillars:

• Adoption,

• Adaptation,

• Assurance, and

• Accountability (20).

DOJ and FDA Join Forces Falsifying Clinical Trials Data

A doctor and two staff members of a medical research center were charged with their alleged scheme to falsify data in clinical trials of prospective new drug treatments. A third staff member was also charged in a criminal information. The defendants allegedly fabricated testing data and falsified other records while conducting clinical trials sponsored by a pharmaceutical development company. The trials were designed to test prospective new drugs to evaluate their safety and efficacy for potential approval by the FDA.

Further, the defendants allegedly used identification documents from people, who did not actually participate in trials, to create false records purporting to show those individuals participated and generated test results. The indictment also alleges that the scheme caused the falsified test data to be submitted into the clinical trial database systems used for evaluating prospective new drugs (21).

U.S. Senate HELP Committee on Largest Public Health System’s Recent Cybersecurity Breach

The U.S. Senate Health, Education, Labor, and Pensions (HELP) Committee pressed on the recent cybersecurity incident affecting NYC Health + Hospitals, the largest public health system in the U.S. Over a three-month period, NYC Health + Hospitals allowed hostile actors access to over one million patients’ health insurance information, medical information, biometric information, precise geolocation data, and Social Security numbers. Earlier this Congress, the HELP Committee passed Cassidy’s Health Care Cybersecurity and Resilience Act to safeguard Americans’ health data. The Committee wrote a letter to the CEO of the NYC Health + Hospitals about the incident (22).

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The OSTP RFI that Stopped the Research Community in its Tracks

In November 2025, the Office of Science and Technology Policy (OSTP) issued a Request for Information (RFI) on Accelerating the American Scientific Enterprise. OSTP was not merely seeking feedback on a single program or agency initiative. It was asking a broader question: How should the federal government strengthen America’s scientific enterprise to ensure continued leadership in discovery, innovation, and technological competitiveness?

More than 12,000 comments were submitted. Universities, scientific societies, research administrators, policy organizations, and advocacy groups offered recommendations on everything from research funding and artificial intelligence (AI) to technology transfer and regulatory reform. Public policy research advocates from Public Responsibility in Medicine and Research (PRIM&R)/Association for the Accreditation of Human Research Protection Programs (AAHRPP), the Council on Governmental Relations (COGR), the Association of Public and Land-grant Universities (APLU), the American Association for the Advancement of Science (AAAS), and the National Academies of Sciences, Engineering, and Medicine (NASEM) provided substantial feedback and recommendations related to:

• Reshaping federal funding mechanisms,

• Leveraging emerging technologies towards the advancement of research, and

• Eliminating unnecessary regulatory barriers to reduce administrative burden.

Although these organizations represent different research policy interests, their responses reveal several common themes. Stakeholders repeatedly emphasized reducing unnecessary administrative burden, strengthening research infrastructure, supporting responsible adoption of AI, improving funding mechanisms, and preserving rigorous merit-based scientific review.

Several months later, the Office of Management and Budget (OMB) released a sweeping proposal to revise the federal government’s grants management framework. OMB characterized the proposal as a necessary effort to strengthen accountability, transparency, oversight, and stewardship of taxpayer resources. The proposed changes would affect virtually every institution that receives federal funding, including universities, hospitals, research institutes, and nonprofit organizations.

Both OSTP and OMB agencies are operating under the same administration. Both are concerned with the future of American science. Both recognize intensifying global competition and the need for a strong research enterprise.

However, when one compares what the research community told OSTP with what OMB has proposed, a notable tension emerges.

What OSTP Asked

The OSTP RFI begins from the premise that scientific leadership can’t be taken for granted. The document notes that America’s scientific enterprise has historically been fueled by institutional innovation. From the creation of major research universities and national laboratories to the establishment of venture capital ecosystems, the U.S. has repeatedly reinvented the structures that support scientific discovery.

At the same time, OSTP acknowledges that science is changing.

AI is transforming research workflows. New institutional models are emerging outside traditional academic structures. Scientific questions increasingly require interdisciplinary collaboration. Global competitors are investing heavily in research and development. These developments raise important questions about whether existing federal policies remain well suited to the needs of modern science. The questions posed by OSTP reflect:

• How can public-private partnerships be strengthened?

• How can scientific discoveries move more efficiently from laboratories to practical applications?

• How can federal grantmaking be improved?

• How should policymakers support high-risk, high-reward research?

• How can AI accelerate discovery?

• Which regulations create unnecessary barriers to scientific progress?

• How can research security be strengthened while minimizing compliance burdens?

What the Research Community Told OSTP

The responses submitted by research organizations reveal a remarkable degree of convergence. Although different groups emphasized different priorities, several aforementioned themes appeared.

Administrative burden is slowing science

One of the clearest messages involved administrative burden. PRIM&R and AAHRPP highlighted NASEM’s report, Simplifying Research Regulations and Policies: Optimizing American Science. APLU similarly pointed to duplicative requirements, inconsistent federal definitions, and the lack of risk-based approaches across agencies. NASEM itself emphasized that its report identified dozens of reforms intended to preserve essential oversight while reducing unnecessary complexity.

This distinction is important. The organizations responding to OSTP were not calling for the elimination of oversight. They were calling for more effective oversight. Across the research ecosystem, investigators, administrators, and compliance professionals increasingly report that excessive complexity consumes resources that could otherwise support discovery.

Sustainable research requires sustainable funding

PRIM&R and AAHRPP advocated for policies that would improve researchers’ access to facilities, equipment, and research resources. COGR argued that institutions must be reimbursed for the full costs of conducting federally sponsored research, warning that continued pressure on indirect cost recovery could undermine the long-term sustainability of research programs. APLU similarly emphasized strengthening partnerships among universities, industry, and government.

AI is an opportunity, not merely a challenge

APLU recommended the development of frameworks identifying which scientific tasks are appropriate for AI assistance, human oversight, or full automation. PRIM&R and AAHRPP advocated for expert panels that could develop standards and best practices governing the use of AI in research. NASEM emphasized the potential for foundation models and advanced AI systems to transform scientific discovery.

Preserve scientific expertise

AAAS emphasized strengthening merit-based peer review. Other organizations similarly highlighted the importance of evidence-based decision making and expert evaluation. The message was clear. If policymakers want better science, scientific expertise must remain central to decisions about research funding and priorities. Taken together, the responses present a relatively coherent vision.

What OMB Proposed

The OMB proposal approaches the research enterprise from a different perspective. Rather than focusing primarily on scientific productivity, OMB focuses on accountability. The proposal repeatedly emphasizes oversight, transparency, stewardship, and alignment with federal priorities.

OMB argues that stronger controls are necessary to ensure responsible use of taxpayer funds, prevent waste, improve compliance, and maintain public trust.

To achieve these goals, the proposal introduces a range of new requirements and expectations including:

• Expanded disclosure obligations,

• Additional risk reviews,

• Increased scrutiny of foreign affiliations and collaborations,

• Enhanced monitoring requirements, and

• Broader authority for agencies to oversee award recipients.

The proposal also emphasizes that peer review should remain advisory rather than determinative, with agency officials ultimately responsible for funding decisions.

Areas of Alignment

OMB's proposal is not entirely disconnected from concerns raised through the OSTP process.

Research Security

OSTP specifically asked how federal policies could strengthen research security while minimizing compliance burdens. OMB’s proposal reflects growing concern about foreign influence, technology transfer, and protection of sensitive research. Universities and research organizations have increasingly invested in research security programs over the last several years.

Public Trust and Accountability

Organizations such as PRIM&R and AAHRPP consistently emphasize public trust as a cornerstone of ethical research. OMB’s focus on transparency and accountability is broadly consistent with that objective. Scientific institutions depend on public confidence.

Areas of Tension

The more significant story may lie in the areas where OMB's proposal appears to diverge from priorities emphasized by stakeholders.

More Oversight vs. Less Burden

The organizations responding to OSTP repeatedly called for simplification. They highlighted duplication, complexity, inconsistent requirements, and excessive administrative obligations. OMB’s proposal introduces additional reviews, disclosures, oversight requirements, and compliance mechanisms. Supporters will argue that these requirements are justified by accountability concerns. Critics will argue that they move in the opposite direction from the reforms stakeholders requested.

High-risk Science

OSTP explicitly asked how federal policy could encourage more high-risk, high-reward research. Historically, many transformative discoveries emerged from projects that appeared uncertain, unconventional, or speculative. Systems designed primarily around accountability often struggle with this reality. The more emphasis placed on predictability, measurable outcomes, and risk mitigation, the more difficult it may become to support ambitious research programs whose benefits are uncertain.

Science Judgment and Political Oversight

AAAS and other organizations emphasized merit-based evaluation and scientific expertise. OMB’s proposal reiterates that peer review should inform funding decisions but ultimately remain advisory. Agency officials are expected to ensure alignment with broader policy priorities. This is not a new debate. Federal research funding has always involved both scientific and political considerations.

The question is where the balance should be struck.

What This Means for the Future of Science Policy

The comparison between OSTP’s RFI and OMB’s proposal reveals something larger than disagreement between agencies. It highlights two different theories of how scientific progress occurs.

• One theory emphasizes reducing friction, empowering researchers, supporting innovation, and improving institutional flexibility.

• The other emphasizes accountability, oversight, stewardship, and alignment with public priorities.

Neither theory is entirely wrong. Scientific institutions require public trust. Public trust requires accountability. Scientific discovery depends on creativity, experimentation, and tolerance for uncertainty. Those characteristics often resist bureaucratic control.

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📢Top FDA Developments

Eliminating Unnecessary Animal Testing in Cancer Drugs Draft Guidance

The FDA issued a draft guidance to reduce unnecessary animal testing in nonclinical safety assessments for certain cancer drugs. When finalized, the guidance will provide recommendations for general toxicology studies, including when animal testing may be unnecessary because there is no binding or pharmacologic activity. The FDA requests that public comments to be submitted by July 30, 2026 (1, 2, 3).

ICH and FDA Guidance Harmonization Update

The FDA issued ICH final guidance titled “M15 General Principles for Model-Informed Drug Development.” The guidance provides general recommendations for the planning, model evaluation, and documentation of evidence derived from model-informed drug development (MIDD) (4).

Additionally, the FDA issued another ICH final guidance titled “Q8, Q9, and Q10 Questions and Answers (R5).” Since the Q8, Q9, and Q10 guidance documents were made final, ICH regions have requested clarification on implementation. This Q&A is intended to clarify key issues (5).

⚡FDA Quick Hits

• This month marks the 50th anniversary of the 1976 Medical Device Amendments to the Federal Food, Drug, and Cosmetic Act (FD&C Act) (6).

• Draft guidance issued to help accelerate gene and cellular therapies (7, 8).

• Final guidance issued to exempt certain unclassified medical devices from premarket notification requirements (9).

• Seven rules published related to medical devices (10, 11, 12, 13, 14, 15, 16).

📢Top NIH Developments

More Discussion on Foreign Components

NIH defines “foreign component” broadly as the performance of any significant scientific element or segment of a project outside of the United States, either by the recipient or by a researcher employed by a foreign organization. NIH stresses that the central issue is not whether foreign collaboration occurs, but whether NIH is informed appropriately and approvals are obtained when required (17).

⚡NIH Quick Hits

• Clarification on percent effort and support for career development (K) awards (18).

• Small Business Program webinar on June 9th (19).

• NIH’s Investigational New Drug (IND) application for mitragynine, the primary psychoactive compound found in Mitragyna speciosa (kratom), has taken into effect with the FDA (20).

📢Other Top Developments

White House EO an Advancing AI Innovation and Security

President Trump signed an EO to advance AI innovation to strengthen America’s cybersecurity, protect critical infrastructure, and ensure the United States remains the global leader in AI innovation. The EO directs appropriate agencies to prioritize the cyber defense of National Security Systems, Department of War information systems, and civilian Federal government information systems (21, 22).

⚡Other Quick Hits

• Another EO was signed to make senior Federal leaders that influence policy decisions more accountable to the American people; however, this reduces some traditional civil-service protections (23, 24).

• GAO conducted a study on the federal electronic health record system and provided recommendations to the DOD and Department of Veteran Affairs (25).

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📢Top Developments

HHS’ Proposed Rule on Modified Terminology

The FDA issuing a proposed rule to modify certain terminology in Title 21 of the Code of Federal Regulations (CFR) to comply with Executive Order (E.O.) 14168, “Defending Women From Gender Ideology Extremism and Restoring Biological Truth to the Federal Government,” issued on January 20, 2025. Specifically, this proposed rule, if finalized, will remove the term “gender” and replace it with the term “sex”, along with other editorial changes to improve readability.

FDA’s Launch of One-Day Inspectional Assessments to Strengthen and Expand Oversight

FDA announced its plans for piloting one-day inspectional assessments, as part of a broader initiative to make its inspectional resources more targeted and efficient. The pilot is being conducted across multiple FDA inspectorates, including human and animal foods, biologics, medical products, and clinical research programs. As of late April 2026, the FDA has completed approximately 46 one-day assessments. One-day inspectional assessments are not intended to replace standard FDA inspections.

FDA’s Expansion of AI Capabilities and Finalizes Data Consolidation

FDA launched Elsa 4.0, a significant upgrade to the agency’s internal AI tool available to all FDA staff, from scientific reviewers to investigators. they also consolidated more than 40 disparate application and submission data sources, systems and portals across all their centers into a new platform called HALO (Harmonized AI & Lifecycle Operations for Data).

FDA Postapproval Pregnancy Safety Studies and IRBs

This final guidance provides sponsors and investigators with recommendations on how to design investigations to assess the outcomes in pregnant women exposed to drug and biological products regulated by FDA (i.e., pregnancy safety studies) in the postapproval setting.

An NIH Update on Foreign Influence

In summary, NIH has initiated the following efforts to upload the highest standards of scientific integrity, public accountability, and social responsibility in the conduct of research:

• Foreign Interference Assessment Tool

• Revised Disclosure Forms

• Small Business Program Foreign Risk Assessments

• Research Security Training Certification

Canvas Cybersecurity Attack: What Should IRBs Consider Right Now

Instructure Holdings, Inc. (Instructure), the parent company of the Canvas Learning Management System (Canvas), recently disclosed an ongoing cybersecurity incident affecting Canvas platforms used by K–12 schools and institutions of higher education worldwide.

• This incident involves unauthorized access to usernames, email addresses, course names, enrollment information, and messages.

• A ransomware group identified as ShinyHunters claimed responsibility and repeatedly defaced Canvas login pages with ransom demands

• Per Instructure’s FAQ, core learning data (course content, submissions, credentials) was not compromised.

The U.S. Senate Health, Education, Labor, and Pensions (HELP) Committee wrote a letter to the Instructure’s CEO about the incident requesting a response by May 28, 2026. The Federal Student Aid Office (part of the Department of Education) provided immediate actions for institutions to take.

NIH’s Reminder for NIH-Supported Research Using AI

NIH released three reminders to the extramural research community:

• Limit the number of applications to six that designate the same principal investigator per calendar year, due to the rising numbers of applications generated with AI tools.

• Peer reviewers are prohibited from using generative AI for their study section critiques.

• AI tools may be appropriate to assist in application preparation for specific circumstances, but researchers should be aware of potential risks.

NIH also reminds researchers of what they would consider noncompliance and how researchers can mitigate these potential risks. Further, the Office of Research Integrity (ORI) is developing best practices to prevent AI-related research misconduct and guidance on the appropriate use of AI tools throughout the research process.

HHS on Protecting Children Online and What This Could Mean for IRBs

HHS released a toolkit and advisory on raising national awareness about the growing risks associated with excessive and harmful screen use among young people. “Children today spend more time on screens than sleeping, exercising, or engaging face-to-face with family and friends — and we are seeing the consequences in rising rates of anxiety, depression, obesity, and developmental challenges,” said HHS Secretary Robert F. Kennedy, Jr.

• The advisory highlights warning signs that screen use may be causing harm.

• The toolkit provides steps that families, schools, and community organizations can use immediately to help children develop healthier digital habits.

OMB Proposes to Revise the Guidance for Federal Financial Assistance

Full disclosure that for this particular update, I used AI to help better understand. As I saw someone on LinkedIn wrote, “I used AI to go through this information because Girl it’s a lot.” I’m sure I’m paraphrasing, but you get the point.

OMB aims to revise its Guidance for Federal Financial Assistance to improve government-wide policies and requirements related to the management of grants, cooperative agreements, and other forms of assistance. OMB is proposing revisions that would improve transparency, accountability, and oversight.

ORI Released New Guidance Documents for the Final Rule

ORI issued the following topic-specific guidance to provide institutions with practical resources tailored to meet the complexities of the updated regulation:

• State of mind

• Respondents

• Institutional record best practices

🔗Full Breakdown

100+ additional reference links from this month from HHS, NIH, FDA, and more!

➡️View here: The Federal and Congressional Scoop on Research (May 2026).

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Any questions you may have about legal information within this article should be discussed with your attorney or legal counsel at your institution. SPIRIT is an educational resource ONLY and is not meant to substitute research ethics oversight or approval.

The Paper that Took LinkedIn Through the Roof

I first saw Joel Seah on LinkedIn proudly announce his first authorship paper titled “Chat-IRB for LMICs: an opportunity for ethics review capacity-building and protection against ethics dumping, IRB shopping, and other exploitative research practices—a response to Moodley et al”.

Here, we discuss his perspective on this collaborative effort on a deeper level.

Your paper illustrates how AI can be used as a tool for research oversight. Where exactly do you think the boundary lies between AI assistance and human moral participation?

Depending on how the IRB-user intends to deploy it, the utilisation of “Chat-IRB” — application-specific large language models for research ethics review — can vary considerably. Its uses can range from relatively simple or “mundane” applications to more substantive ones.

For example, simple or ‘low-hanging fruit’ applications like: assisting IRB staff (and/or members) in pre-review screenings, and autonomously generating summaries of IRB applications/study protocols; to more substantive functions like: prompting the IRB to reconsider or provide additional justifications for proposed decisions that deviate from past precedents or ethical guidelines, and providing decisional support to inform the IRB’s ethical analysis on specific issues. And the latter would invariably involve AI outputs that can influence the IRB’s ethical judgements, and consequently, its decisional outcomes (i.e., approval, require modifications, or disapproval) for the proposed research.

Relatedly, I was quoted in Science saying that Chat-IRB “could help you handle your more mundane matters, so that you can focus on the substantial stuff”. But what if there might be good reasons for Chat-IRB to assist with, or “do” the substantial?

As such, I believe that when IRBs start to employ GenAI tools in more substantive ways during their ethics review, they begin to enter the zone of ‘AI for moral deliberation’; particularly if and when Chat-IRB is deployed in an agentic fashion to inform and facilitate — and possibly influence in the process — members’ ethical deliberations during their reviews and discussions such as at convened ‘Full Board’ meetings.

Functionally, it is technically feasible to programme a Chat-IRB that provides IRB-users with ethical analyses and justifications for the approval/modification/disapproval of proposed studies. Accordingly, human participation in such AI-assisted ethical deliberations can range — much like in most forms of AI-assisted decision-making — from substantial to little or no meaningful involvement at all.

Unsurprisingly, deploying Chat-IRB in such a manner raises ethical concerns (e.g., automation bias), especially when its outputs are presented or otherwise perceived as highly logical, accurate, and/or authoritative, such that human reviewers begin to anthropomorphise it as an “expert” and accept its recommendations/suggestions at face value.

At the same time, it also raises the more difficult question of whether some degree of deference to a Chat-IRB that demonstrates strong accuracy and reliability in ethical analysis — and perhaps even in moral deliberation — might be warranted, particularly if and when the IRB lacks substantial ethics expertise within its composition. After all, it is quite unlikely that a brief, one-off minimum ethics training course (e.g., CITI program) would equip one with substantial expertise in ethical analysis.

Your proposal assumes past IRB decisions are valuable training data. Has the study team ever considered integrating their tool with the IRB Precedent Tool? If institutions all adopted the IRB Precedent Tool, how would the study team theoretically account for any inconsistencies, biases, or over-conversative IRB decisions?

As described in our paper, Chat-IRB’s functions such as “preliminary review” and “consistency checking” were framed with ‘IRB precedent’ — or perhaps more appropriately termed, ‘decision summary banks’ — in mind.

Importantly, the introduction of AI should not obfuscate how can and should IRBs operationalise precedent effectively because, the question remains unchanged even in the absence, or non-use, of AI tools; that is to say, how are IRBs to treat banked decisions that are: inconsistent with current proposed decisions; biased; or seemingly over-conservative?

While these are important matters that warrant further analysis and deliberation — and which any precedent project would have to eventually address — here is my brief take:

• On inconsistencies: This is why the term ‘decision summary’ is preferable to ‘precedent’ because, the latter might imply or be misunderstood that the IRB’s (future) decisions are strictly bound to past decisions — e.g., for the sake of consistency. This ought to not be the case. Like judges, IRBs should similarly have the ability to deviate from prior decisions if there exist good and justifiable reasons for doing so, and importantly, to disregard prior decisions that are, in retrospect, considered mistaken or made in error.

• On bias: Beyond ensuring their decision summaries (DS) are of sufficient quality, IRBs should consider conducting periodic audits of their banked DS to identify decisions that may reflect bias or had been made under biased assumptions.

  • This is also an area where AI has an advantage over humans. Human bias during reviews is sometimes difficult to detect, and it is even harder to correct. Being told you are biased does not mean you would be able to easily or immediately correct it, nor can there be any assurance that you would cease to be biased in your views and judgements. By contrast, an AI’s outputs can at least be monitored, audited, and iteratively debiased through evaluation and retraining of the model.

  • Accordingly, when an institution chooses to implement tools such as Chat-IRB, IRB-users and developers should pay close attention to, amongst other things, bias when curating their DS for Chat-IRB’s knowledge base. And if historically biased DS are to be retained in the database to serve as institutional memory, they should at least be flagged accordingly — both to the AI system and to its IRB-users.

• On over-conservativeness: To determine whether an IRB decision is or was “overly conservative” in any objective sense would likely require a comparison against some form of baseline. While challenging as it may be, I think establishing a national-level database of sufficiently anonymised DS, contributed by various IRBs, can potentially assist HRPPs in developing a consensus on what constitutes a reasonable standard of human protections (for a given type of study).

That said, it is also important to remember that, as the saying goes, “it depends”. What may seem over-conservative on its face might in fact be appropriate once you consider the contextual factors of the proposed research — e.g., institutional history, cultural considerations, or the prevailing political climate.

Who should be legally and morally accountable when an AI-assisted IRB decision contributes to participant harm?

In terms of legal liability, this would be an important issue for the legal scholars, practitioners, policy makers, and jurisdictions to resolve. However, it is admittedly not an easy question; we can already observe this in analogous applications of AI such as autonomous/self-driving vehicles, where frameworks for determining liability still appear to be under development.

One potential way forward may be to employ “Collective Reflective Equilibrium in Practice”; a method proposed by Savulescu et al. that utilises public preferences/attitudes to help inform and shape policy on the use of controversial novel technologies. (I mention this merely as a possible approach, and not necessarily as an endorsement of it).

At the same time, this also raises a prior question: how many instances have there actually been where an IRB’s decision was determined to have contributed to participant harm? Put differently, how often has harm to a research subject or participant been directly attributed to an IRB’s action or inaction?

Supposing we can establish with certain confidence that the IRB was in fact responsible for the harm caused, then this table by Price et al., which maps “potential physician liability for clinical use of AI” (Table 9.1 from their chapter “Liability for use of artificial intelligence in medicine”), may provide a useful starting point for thinking through the conditions under which an IRB could or would be liable for the harm caused from AI use in its decision-making (see #2 and #7 of the table).

Quite clearly though, this table does not map neatly onto the IRB’s context. The HRPP field will therefore have to develop its own framework for determining IRB lability in relation to the use of AI-assistance for ethics review and decision-making.

Again, these are merely suggestions. As the technology rapidly evolves — and as institutional adoption of AI increases — so too will our legal frameworks and moral analyses change and adapt accordingly.

From my understanding, reasoning models improve explainability because they expose chain-of-thought reasoning. However, there is also AI research that suggests that this approach may be fragile and unreliable. Why should IRBs trust it?

Just as a note on the notion of ‘trust’. There is some philosophical literature on why it would be inappropriate to trust AI in the same way we would trust a human person, and that we should be ‘relying’ on AI instead. Briefly, trust has a relational property (between two agents). So, until AI can be held accountable or responsible for their actions/outputs in ways humans can, it would be more appropriate to ask, “Why should we rely on AI?” rather than, “Why should we trust it?”.

Now, until we possess validated GenAI tools (e.g., LLMs, Reasoners, Agentic AI) that are purpose-built for ethics review, and that achieve accepted, reproducible levels of accuracy and reliability in their outputs and/or Chain-of-Thought (CoT) — similar to the kinds of validation standards expected of for clinical AI — I do not think IRBs should treat a reasoner’s CoT as a panacea for explainability.

That said, this does not mean CoTs are ineffectual or “worthless”. Compared to older models, like the now-retired ChatGPT-4o, which provide end-users with only its final output, a reasoner’s CoT provides at least a certain degree of interpretability regarding how their responses came to be. This permits the human user to assess and determine if the AI might have “hallucinated” its output or made logic errors.

Unsurprisingly, this in turn raises the question of whether the human user possesses the level of expertise required to adequately evaluate the CoT (and the resulting output). Consequently, this relates back to my earlier point regarding appropriate deference to an accurate and reliable AI. What happens if the human user lacks the necessary expertise to critically evaluate the AI’s reasoning and conclusions?

If AI tools in ethics review are indeed inevitable, then it is imperative that institutions begin critically examining the kinds of domain expertise required within their IRBs and their composition, to competently evaluate the outputs of GenAI used in support of, or to augment their ethical judgements, before it is too late.

IRBs are already criticized for potential delays in starting research. Could AI systems unintentionally intensify oversight by generating more flags, more caution, and more procedural scrutiny?

I find statements such as “the IRB delayed my study” to be a somewhat sweeping claim that does not do justice to the many challenges IRBs face in trying to fulfil their mandate.

To be clear, I am not suggesting IRBs are guiltless. But the causes of delays are often nuanced, multifactorial, and sometimes interrelated with knock-on effects, such that it can be unfair to attribute delays to any single point alone. Contributors to extended turnaround times can range from things like:

• Sub-optimal staff/member-to-application ratio (i.e., inadequate manpower);

• Protracted response times from both researchers and IRBs, especially when the latter are short-handed;

• Poorly written submissions, missing documents, and/or discrepancies within the IRB application;

• Insufficient knowledge or understanding of ethical, institutional, and/or regulatory requirements;

• Poor communication strategies in explaining what is required of researchers — and importantly, the reasons why — owing in part to complex regulatory language; and

• Perhaps more controversially, disagreements between the IRB and researchers on what safeguards or restrictions are ethically necessary or justified.

The last point is particularly contentious. IRBs may believe that certain safeguards, alternative procedures, and/or restrictions are necessary to adequately protect participants, or that certain interventions are ethically impermissible because they are too risky. While researchers on the other hand may believe that the IRB’s concerns are unfounded, overly conservative, or insufficiently justified, and that such requirements or changes mandated by the IRB ultimately prevent them from collecting data crucial to answering their research questions.

I believe a well-designed and reliable Chat-IRB would potentially address many of the points raised above. Whether it could help ameliorate or resolve the impasse described in the last point however remains to be seen, though I am cautiously optimistic. For example, it may help IRBs better articulate and justify the rationale underlying their decisions to researchers. Conversely, it could provide IRBs with supporting literature, empirical information, and/or ethical analyses that suggest why their initial assumptions, interpretations, or judgements might be mistaken.

Ultimately, whether Chat-IRB might cause unnecessary delays in securing ethics approval will depend significantly on how, and at which stage of the ethics review process, does the IRB choose to deploy it.

If an IRB determines that delays are arising from AI utilisation, it should then examine the nature of those delays. If the delay stems from the AI identifying ethically (or legally) relevant concerns that the IRB had previously overlooked or insufficiently examined in similar (past) protocols, then such delays would in fact be ethically warranted. In this instance, the AI is helping the IRB better fulfil its societal moral mandate: protecting human research participants, and serving as gatekeepers for the ethical conduct of research.

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DISCLAIMER

Any questions you may have about legal information within this article should be discussed with your attorney or legal counsel at your institution. SPIRIT is an educational resource ONLY and is not meant to substitute research ethics oversight or approval. The views and opinions expressed here are solely from the interviewee (Rekha Kota) and do not represent those of her institution or any affiliated organization.

How do I know Rekha?

Well, from LinkedIn of course!

Rekha has 23 years of experience in the medical field specializing in optimizing workflows, improving data quality, and fostering effective team collaboration to support medical research, patient care, and regulatory compliance. Her background includes clinical trial data management, laboratory operations, regulatory oversight, and quality assurance, with a strong focus on efficiency, accuracy, and compliance.

In her current role, she oversees ClinicalTrials.gov registration, maintenance, and compliance across Mass General Brigham, ensuring adherence to FDAAA‑801, NIH, CMS, ICJME, IRB, and institutional requirements. Rekha focuses on:

• Managing ClinicalTrials.gov records and ensure institution‑wide compliance,

  Reviewing protocols to determine registration and results‑reporting requirements,

  Developing educational materials, trainings, and communication strategies,

• Collaborating with IT to improve tracking systems and compliance monitoring,

  Addressing noncompliance and escalate issues to leadership when needed,

• Maintaining policies/SOPs and recommend corrective actions,

• Liaising with NIH ClinicalTrials.gov, and

  Providing high‑level support to investigators and serve on IRB ancillary review.

In this interview, we will learn about the intricacies of ClinicalTrials.gov.

What do most research teams misunderstand about ClinicalTrials.gov?

A common misconception among study teams is that completion of ClinicalTrials.gov registration marks the end of their regulatory responsibilities for that record.

In practice, many institutional policies emphasize front end compliance, such as initial registration, as part of the initial IRB approval process. This ensures that study teams meet baseline requirements at study initiation.

However, this focus can inadvertently create a gap in understanding regarding ongoing obligations.

As a result, compliance efforts often diminish after initial registration, highlighting the need for greater awareness and institutional reinforcement of post registration responsibilities throughout the study lifecycle.

What is the most common error you see on a record?

A consistent challenge is the lack of ongoing record maintenance after initial registration.

At the time of registration, often before the study has even begun, study teams are required to provide anticipated dates such as the study start date, primary completion date, and study completion date.

Following initial IRB approval, there is an expectation that teams will update the record to reflect the following within 30 days of change:

• Current study status,

• IRB approval information, and

• Any revised timelines within 30 days of the change.

However, this responsibility is frequently overlooked. As studies progress, the initially provided dates may lapse without updates, resulting in the record becoming outdated.

This pattern reinforces that compliance is not limited to initial registration but requires active and ongoing management to ensure accuracy throughout the lifecycle of the study.

What are the biggest operational mistakes study teams make with result reporting timelines?

Although registration timelines may vary across regulatory bodies such as the FDA, NIH, and PCORI, results reporting timelines are notably consistent.

A common issue is that study teams often underestimate this requirement by not fully accounting for the time needed to complete data analysis. As a result, records frequently fall out of compliance.

Data analysis typically requires significant coordination among study teams, statisticians, and data coordinators, and can be a time intensive process.

To address this challenge, it is essential that study teams are educated early in the study lifecycle that the 12-month reporting timeline includes both data analysis and reporting activities.

With this understanding in place from the onset, teams are better positioned to plan accordingly, allocate sufficient time and resources, and maintain compliance. Proactive planning is critical to ensure that both analysis and reporting are completed within the required timeframe.

What role should IRBs and HRPPs play in ClinicalTrials.gov oversight?

Many institutional policies appropriately incorporate ClinicalTrials.gov requirements into the IRB process, which is a strong foundation for compliance. However, the level of integration can vary significantly by institution.

Some institutions engage with ClinicalTrials.gov activities at multiple points throughout the study lifecycle, while others focus primarily on initial registration and/or final results reporting.

Expanding the integration of ClinicalTrials.gov requirements into ongoing IRB processes can substantially improve compliance.

Although this integration may slightly increase the regulatory workload, it ultimately supports more consistent compliance and reduces the risk of regulatory findings.

• With increasing scrutiny from regulatory agencies, maintaining accurate and up to date ClinicalTrials.gov records are critical.

• Embedding these responsibilities within familiar IRB processes helps streamline workflow, promotes accountability, and enables study teams to manage their obligations more effectively across the full study lifecycle.

What policies or workflows separate study team ClinicalTrials.gov compliance from those constantly struggling?

Ongoing maintenance of the study record and a clear understanding of regulatory expectations are essential components of compliance.

Many institutions have taken positive steps by incorporating ClinicalTrials.gov training as a mandatory component of initial onboarding for clinical research teams. In addition, institutions often provide resources to guide study teams through the full process, including registration, record maintenance, and results reporting when applicable. However, access to training and resources alone is not sufficient. The key issue is awareness and consistent application of that knowledge throughout the study lifecycle.

Study teams already embed IRB processes into their regular workflows as a standard practice. Applying the same discipline to ClinicalTrials.gov requirements can significantly streamline compliance efforts and reduce the likelihood of last-minute challenges.

Addressing ClinicalTrials.gov obligations early and consistently is far more efficient than attempting to resolve compliance issues at the end of a study, when teams are already managing multiple competing regulatory requirements associated with study closeout. A simple but critical step is regular record maintenance.

With increasing regulatory scrutiny and heightened enforcement actions from agencies such as the FDA and NIH for noncompliance, education and accountability are more important than ever. Study teams must recognize the significance of ClinicalTrials.gov requirements and approach these responsibilities with the same level of attention and rigor as other regulatory obligations.

What are examples of noncompliance with ClinicalTrials.gov?

Several recurring issues can affect ClinicalTrials.gov compliance, many of which stem from gaps in ongoing record maintenance and awareness of regulatory expectations.

Erroneous records or records that lack updates

These are among the most common issues observed.

They typically result from a failure to maintain the record after initial registration. As noted earlier, study teams are required to provide anticipated dates at registration, including the study start date, primary completion date, and study completion date. When these dates pass without being updated to reflect the current status of the study, the record becomes outdated and is automatically flagged as “Not Recently Updated.”

This type of error is a clear indicator of inadequate record maintenance and highlights the importance of routinely reviewing and updating ClinicalTrials.gov records throughout the study lifecycle.

FDAAA Late Results

Another significant compliance issue is the “FDAAA Late Results” flag.

Once the actual primary completion date has been updated on the record, results are generally required to be reported within 12 months of that date if study meets certain criteria. If results are not submitted for those studies, or if submitted results are incomplete, the record may be flagged for late results under FDAAA requirements. This is a serious compliance concern. For studies conducted under an IND/IDE application, there is increased regulatory scrutiny and oversight by the FDA. Noncompliance may result in formal notification letters, which are publicly posted on the FDA’s noncompliance webpage. This level of transparency can have reputational implications for investigators and institutions.

NIH-Funded Study Challenges

For studies funded partially or completely by the NIH but not subject to FDA regulation, tracking results reporting timelines can be more complex.

These studies may not trigger FDAAA late results flags within ClinicalTrials.gov if they do not meet specific applicability criteria for FDA regulated products. As a result, principal investigators cannot rely solely on system generated alerts to monitor compliance.

In these cases, responsibility for tracking reporting deadlines rests entirely with the PI/study team. The NIH maintains its own oversight mechanisms and may issue noncompliance notifications if results are not reported within required timelines.

Across all scenarios, the underlying theme is the same. PIs must take active ownership of their ClinicalTrials.gov records. Regular updates, proactive tracking of key dates, and a clear understanding of regulatory expectations are essential. Relying on system flags alone is not sufficient. Consistent oversight and early planning are critical to maintaining compliance and avoiding regulatory consequences.

What is the primary key takeaway from this topic?

ClinicalTrials.gov compliance is not a one-time task but an ongoing responsibility that requires active management throughout the entire study lifecycle.

The most important takeaway is that success depends on:

• Early education,

• Consistent record maintenance, and

• Proactive planning for results reporting.

Study teams must understand from the start that responsibilities extend well beyond initial registration and include timely updates, accurate tracking of key dates, and results reporting within required timelines.

Integrating these responsibilities into routine workflows, especially alongside IRB processes, makes compliance more sustainable and reduces the risk of errors, outdated records, and regulatory findings.

In simple terms, plan ahead, update regularly, and treat ClinicalTrials.gov requirements with the same priority as other regulatory obligations.

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DISCLAIMER

Any questions you may have about legal information within this article should be discussed with your attorney or legal counsel at your institution. SPIRIT is an educational resource ONLY and is not meant to substitute research ethics oversight or approval.

Oh where, oh where is OHRP? Oh where, oh where could they be?

OHRP’s LinkedIn disappears without a trace

For those unaware:

• OHRP stands for the Office of Human Research Protections.

Am I the only one who remembers tagging OHRP on LinkedIn?

Back when OHRP was fully staffed before the massacre happened, I remember tagging OHRP quite a bit. I’m kicking myself because I saw a post from OASH (which will be defined later) that OHRP’s LinkedIn would be taken down (which would have been an excellent screenshot to include in this article).

However, when you go to OASH’s LinkedIn page something interesting happens…

Under “Posts > All”, we see nothing.

Very strange.

But…

Under “Images” and even “Videos”, we can see that there was clearly activity on LinkedIn…

Going back to OHRP’s LinkedIn page…

For those who don’t remember, OHRP had a LinkedIn page!

This wasn’t a hallucination. In fact, when you try to click the LinkedIn page, this is what you see:

I even tried to look up previous employees that I knew worked at OHRP to see if I could find their page. Interestingly, I only found this page: Public Health.

OHRP now offers Human Research Protections (HRP) training via CDC TRAIN

For those unaware:

• CDC stands for Centers for Disease Control and Prevention.

• TRAIN is a national learning network that provides quality training opportunities for professionals who protect and improve the public’s health.

Based on their last newsletter (which will be a point of discussion shortly), TRAIN makes the content easier to find and access for state, tribal, territorial, and local health departments; public health institutes; federally qualified health centers; students; and other public health professionals.

Another interesting quote: “As a TRAIN affiliate, CDC can also add additional HRP trainings as needed.”

This makes me curious about OHRP’s overall contribution to training efforts (without external collaborators) - given the reduction in staff.

Is this why there is a push to make public health professionals aware of this space?

Lack of OHRP news, but variability in determination letters

Compliments of Google Gemini, I asked this nifty tool to create a visual chart of OHRP’s newsletters and determination letters over time. I went based off the newsletters as these started in 2022; I’m aware that determination letters go farther back. I find it curious that the same year we had a change in administration, we see the most variability in these numbers. Given the various reports on OHRP’s staff cuts, it makes sense that their efforts would be geared more towards enforcement.

However, it seems like OHRP may need some reinforcement (no pun intended) if they are going to issue any determination letters this year.

Interestingly in 2023, OHRP didn’t issue its first letter until June.

Only time will tell…

OHRP’s and CDC’s current structure

OHRP is currently organized as an office under OASH under the HHS OS

Even more acronyms:

• OASH stands for Office of the Assistant Secretary for Health.

• HHS stands for Department of Health and Human Services.

• OS stands for Office of the Secretary.

OS supports the HHS Secretary by overseeing operations, providing guidance, and ensuring laws are followed fairly. Their focus is on public health, health care, and human services. OASH is an office under the OS.

Within OASH, we have two critical organizations pertaining to research compliance (directly copied from the website):

• OHRP

• Office of Research Integrity (ORI) - I know, another acronym.

CDC is a division of HHS

Divisions within the HHS administer a wide variety of health and human services and conduct life-saving research for the nation. The CDC specifically serves the American public—individuals, families, and communities—who rely on accurate data, health guidance, and preventive measures.

Understanding the HHS FY27 Budget in Brief

CDC has its own budget, so what about OHRP?

Under the proposed FY27 budget, OHRP will be one of the research protections offices in ASCRA.

Assistant Secretary for Civil Rights and Appeals (ASCRA): who is this?

ASCRA’s mission is to serve as a unified guardian of American health, rights, and research. ASCRA is committed to ensuring that all services provided under HHS are administered with the highest levels of fairness, accountability, compliance, and integrity. ASCRA will carry out legal compliance through enforcement and adjudication in the healthcare environment under all federal statutes and regulations, including civil rights laws, Medicare appeals statutes, and administrative law authorities.

ASCRA, ORI, OCR, OHRP, and OARP: will this alphabet soup be good for the soul?

I.e., what would federal research compliance potentially look like under this new umbrella?

Last set of acronyms (I hope):

• ORI stands for Office of Research Integrity.

• OCR stands for Office for Civil Rights.

• OARP stands for the newly proposed Office for Animal Research Protections.

Per ORI’s website, ORI oversees and directs Public Health Service (PHS) research integrity activities on behalf of the Secretary of Health and Human Services with the exception of the regulatory research integrity activities of the FDA.

Per OCR’s website, OCR enforces federal civil rights laws, conscience and religious freedom laws, the Health Insurance Portability and Accountability Act (HIPAA) Privacy, Security, and Breach Notification Rules, and the Patient Safety Act and Rule, which together protect your fundamental rights of nondiscrimination, conscience, religious freedom, and health information privacy.

Under OARP, there is a very small snippet of what this office will do:

OARP will help to ensure that animal research supported by HHS can ethically and humanely deliver compliant, trustworthy data that advances health.

Sadly, my final question left me with more questions; I’m hoping this resonates with you.

Under this new umbrella☂️:

1. Could Health Insurance Portability and Accountability Act (HIPAA)-related studies be under greater scrutiny?

2. Where will Institutional Review Board (IRB) and Responsible Conduct of Research (RCR) committees intersect with studies including artificial intelligence (AI) and potential research misconduct?

3. Could exempt four categories be revised to be under limited IRB review (as some other exempt categories under the Common Rule)?

4. What are the implications to decentralized clinical trials (DCTs) that use digital health as a mode of data collection (e.g., a wearable)?

5. When will IRBs realize the expertise of emerging technologies and privacy concerns needs to be a requirement for either a board member or to consistently collaborate with subject matter experts (SMEs)?

6. How do we truly define “minimal risk” in the age of these chilling technologies?

7. I realize the budget includes OHRP educational materials, but I question if this will truly happen. What do you think?

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DISCLAIMER

Any questions you may have about legal information within this article should be discussed with your attorney or legal counsel at your institution. SPIRIT is an educational resource ONLY and is not meant to substitute research ethics oversight or approval.

📢Top Developments

NIH’s Reminder for NIH-Supported Research Using AI

NIH released three reminders to the extramural research community:

• Limit the number of applications to six that designate the same principal investigator per calendar year, due to the rising numbers of applications generated with AI tools.

• Peer reviewers are prohibited from using generative AI for their study section critiques.

• AI tools may be appropriate to assist in application preparation for specific circumstances, but researchers should be aware of potential risks.

NIH also reminds researchers of what they would consider noncompliance and how researchers can mitigate these potential risks. Further, the Office of Research Integrity (ORI) is developing best practices to prevent AI-related research misconduct and guidance on the appropriate use of AI tools throughout the research process.

IRB Regulatory Insight

GAO Spotlight on Privacy Enhancing Technologies

The Government Accountability Office (GAO) reported on Privacy enhancing technologies, or PETs, which can help reduce risks associated with collecting, using, and sharing data. They also could enable more secure collaboration and research on sensitive information, such as medical records or proprietary company data.

• PETs modify, hide, or process data in ways that make it difficult to access sensitive information.

• PETs could enable responsible deployment of AI and other applications that are using increasing amounts of personal data; therefore, reducing data privacy risks.

• Though PETs sound promising, they are expensive and there is also lack of federal guidance.

IRB Regulatory Insight

HHS on Protecting Children Online and What This Could Mean for IRBs

HHS released a toolkit and advisory on raising national awareness about the growing risks associated with excessive and harmful screen use among young people. “Children today spend more time on screens than sleeping, exercising, or engaging face-to-face with family and friends — and we are seeing the consequences in rising rates of anxiety, depression, obesity, and developmental challenges,” said HHS Secretary Robert F. Kennedy, Jr.

• The advisory highlights warning signs that screen use may be causing harm.

• The toolkit provides steps that families, schools, and community organizations can use immediately to help children develop healthier digital habits.

IRB Regulatory Insight

🔗Full Breakdown

15+ additional updates this week, including:

⚡Senate Health, Education, Labor, and Pension (HELP) Committee concerns on national security threats against American universities

⚡NIH’s continued commitment to fundamental research

⚡ HHS re-org of the Office for Civil Rights (OCR)

➡️View the curated list here: The Science Policy Scoop (Week of May 18, 2026).

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