Our efforts to improve the quality of the clinical trials enterprise, with a particular focus on academic trials, continue along two main streams: improving the public reporting of individual clinical trials and ensuring that the evolving evidence base is used optimally to inform future research, policy, and clinical decision-making.

Work to improve the reporting of individual clinical trials included a publication aimed at improving methods for reporting master protocol research designs. Master protocols often do not have a clear “study start date” and “study completion date” date, anticipated by registries such as ClinicalTrials.gov, but rather an overall design that permits study arms to open, close, and evolve with emerging evidence. Registration and reporting, therefore, has been challenging. We are also monitoring results reporting rates for different funder types, an analysis that reveals the impact of various policies (e.g., ICMJE requirements) and the degree to which there is need for improvement.

The MRCT Center’s key efforts related to the second stream—ensuring optimal use of the evidence base—consisted of a multi-pronged project designed to assess and make recommendations related to avoiding the initiation and continuation of low value trials, particularly when there is evidence from prior research that the new “index” trial would likely be uninformative. Through the mixed methods approach (e.g., literature review, focused interviews, and a modified Delphi consensus panel), we developed shared standards for literature review and analyses of the therapeutic landscape relevant to the study (i.e.,  ‘landscape analysis’), to help ensure that new clinical trials are informed by earlier research.  Related projects included analyses of informed consent forms and protocols in order to focus efforts at quality improvement.

In 2023, we plan to focus on incentive systems to ensure complete reporting of clinical trial results and how to further improve the reporting of complex trial designs.  Efforts to improve the use of the evidence base will focus on developing tools to aid in the conduct and documentation of Landscape Analyses in order to support effective oversight.  In addition, we are analyzing the description of data monitoring plans in trial protocols and beginning to explore methods for studying the functioning of data monitoring committees.

Explore Advancing the Quality of Clinical Trial Enterprise.

The challenges of moving pediatric medicines from regulatory approval to market access emerged as a key challenge in the pediatric work group discussions.

Following a series of preliminary meetings in March, May, and November 2022, we plan to host a two-day conference entitled, “Access to Medicines for Children: From Regulatory Approval to HTA (Health Technology Assessment) Review,” at The Brocher Foundation in Hermance, Switzerland, on 24-25 January 2023. The intent of the small group discussions is to gain clarity and mutual understanding of the different ethical aspects, responsibilities, evidentiary requirements, and scientific methodologies of regulatory and HTA decision-making that can lead to different decisions and thus differential access to medicines for children.

The MRCT Center continues to work with and respond to in-country stakeholders to deliver dynamic, practical, and sustainable training courses for regulators, ethics committees, data safety committees, and clinical site investigators staff.

In 2022, the MRCT Center developed and delivered virtual trainings to audiences around the world.

• In partnership with the African Vaccine Regulatory Forum (AVAREF) and support from the Bill and Melinda Gates Foundation, the MRCT Center conducted training courses for Ethics Review of Clinical Research. Committing to a train-the-trainer model, ethics committee chairs and members from 25 countries across Africa participated in virtual lectures and case study group discussion.
• In the Philippines, in collaboration with the National Institutes of Health at the University of the Philippines in Manila, members of a newly established Data Safety Monitoring Committee (DSMC) were trained in the responsibilities of a DSMC.
• In collaboration with Pfizer Indonesia, lecturers from public and private universities who teach in undergraduate and graduate biotechnology degree programs were inspired by lessons on real world data, genomics, and research ethics.

In 2022, the MRCT Center expanded its offering of online learning:

• A six-part training, “Equity by Design in Clinical Research,” which was initially delivered as a live virtual course, was made available online to advance diversity, equity, and inclusion of underrepresented populations in clinical trials.
• “IRB Health Literacy in Clinical Research” introduces the concept of health literacy and how it applies to the review and approval of clinical research.
• The successful “Interpretation and Application of ICH GCP E6(R2)” training continues to attract 40-50 individuals from around the world each month. Since its inception in early 2020, more than 3,200 individuals have enrolled and more than 2,000 individuals have completed all ten modules.

Upcoming trainings in 2023 include:

• Commissioned by the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH): an overview and training modules on ICH E8 (R1): General Considerations for Clinical Trials
• With the support of the Bill & Melinda Gates Foundation and the World Health Organization: capacity building for ethics committees across Africa through the development of an online, on-demand training course.
• Health literacy online training for sponsors, research study teams and CROs.
• Online training for research teams at academic medical centers on how to return summary study results to participants.

Patients and participants remain central to the work of the MRCT Center as we continue to champion ethical, well-conducted research grounded in participant involvement and engagement.  As such, provision of accurate health and research information in plain language will help people identify and understand options before them.

In 2022, the MRCT Center developed and disseminated new educational research materials for young people, shown here.  Additionally, we are delighted to share videos, some developed in partnership with Dr. Gianna “Gigi” McMillan, Associate Director for the Bioethics Institute at Loyola Marymount University (click here to view), and others with iCAN (International Children’s Advisory Network – click here, here and here), that highlight the importance of youth input in clinical research.

The MRCT Center developed a short document that suggests questions that patients and participants might ask their study teams about the costs of and payments associated with participating in a clinical research.

We partner with patients and patient advocates to advance important issues in the clinical research space. Jamie Tyrone, author, research participant, and patient advocate, helped us narrate a video on the benefits and potential risks of participant use of social media. Her blog post explains the process and learnings.  This blog post, advising on how to navigate social media as a research participant, is emblematic of the types of partnerships we continue to prioritize in our work with patients.

Work on the MRCT Center plain language Clinical Research Glossary has expanded in 2022. The expanded glossary, co-developed with a diverse multi-stakeholder workgroup, will be released in the coming year.

Access our Patients and Participants Resources.

The patchwork of privacy laws that apply to the processing of personal data, including clinical trial and health data, can restrict the transfer of such data across national boundaries and impede the progress of science and public health, as well as the use of personal data for secondary research. In addition to European Union’s General Data Protection Regulation (GDPR), a growing number of sector-specific and omnibus state privacy laws have been enacted, as well as country-specific omnibus privacy laws (e.g., China’s Personal Information Protection Law). The MRCT Center remains at the forefront of analyzing and understanding the impact of these emerging data and biospecimen sharing and privacy laws and regulations.

In June 2022, the MRCT Center and Ropes & Gray LL held a virtual meeting of the Research, Development, and Regulatory Roundtable (R3) to discuss recent developments with respect to GDPR and research with representatives.  The presentation included representatives from the U.S. government involved in negotiating the Trans-Atlantic Data Privacy Framework that the Biden administration announced in March 2022 and for which an Executive Order was issued in October 2022.  In December 2022 the MRCT Center and Ropes & Gray LLP hosted a one-day hybrid meeting of the Research, Development, and Regulatory Roundtable (R3) to discuss various issues related to data sharing and privacy. The first panel addressed regulatory issues in areas outside the U.S. and European Economic Area, while the other four focused on issues related to GDPR.

Review the Impact of Privacy Laws on Clinical Research initiative.

The MRCT Center remains dedicated to advancing Diversity, Equity, and Inclusion (DEI) in Clinical Research. The release of the MRCT Center’s Achieving Diversity, Inclusion, and Equity in Clinical Research Guidance Document in 2020 laid the foundation; continued focus was and is necessary to sustain change.

In 2022 and in response to requests, the MRCT Center launched a live six-module short course that was later reformatted into a continuous online curriculum entitled, Equity by Design in Clinical Research: A Six-Part Course. In partnership with others, the MRCT Center released the Equity by Design (EbD) in Clinical Research Metrics Framework to help stakeholders evaluate and implement processes to advance DEI in clinical research. Complementary to the efforts focused on clinical research practitioners and professionals, the Center also released its IRB and HRPP Toolkit, a suite of tools and resources designed to support IRBs and human research protection programs (HRPPs) advance DEI efforts in clinical research.

This year, in collaboration with others, the MRCT Center has focused on inclusion of people with disabilities in clinical research, first by calling attention to broad eligibility criteria that results in exclusion of people with disabilities. We published empirical data that identified areas of needed change. We have described the utility of supported decision-making in clinical research to preserve autonomous decision making by people with cognitive and intellectual disabilities where possible.  We are finalizing an “Accessibility by Design in Clinical Research” toolkit that aims to provide practical tools for sponsors, researchers, and IRBs to use to increase the inclusion of people with disabilities.

Lastly, in response to stakeholder requests for application of DEI best practices globally, the MRCT Center is working to understand the different challenges that regulators, sponsors, investigators, and study teams face internationally when considering diversity and inclusion in clinical research.

See the Diversity, Inclusion, and Equity in Clinical Research initiative.

The COVID-19 pandemic highlighted the need for clear, understandable communications about medicine and research. The MRCT Center has focused on health literacy in clinical research and on developing resources to support all stakeholders along the research continuum.

In 2022, the MRCT Center disseminated educational sessions related to the principles and practices of health literacy to academic centers, industry partners, and other organizations. The successful launch of a free, online health literacy training for IRBs in 2022 will be coupled by a general health literacy training for investigators, study teams, and contract research organizations to be released in 2023.

The Clinical Research Glossary, launched in 2021, was expanded this year, and the expansion was again co-created with patients and patient advocates. The larger, more comprehensive, and sustained resource will be released in 2023.

Learn more about Health Literacy in Clinical Research, and the Clinical Research Glossary.

In 2017, the MRCT Center released a framework that outlined the post-trial responsibilities (PTR) to a research participant at the end of participation in a clinical trial. The framework included principles, a guidance document, and toolkit, and provided a case-based, stakeholder approach to evaluate ethical responsibilities for continued access of an investigational product.

After five years, implementation challenges have emerged, and the growing importance of in post-trial responsibilities by all stakeholders of the global clinical trial enterprise are compelling reasons to update the framework. In addition, post-trial responsibilities of implanted devices, a topic not addressed previously, raise new issues. In the summer of 2022, the MRCT Center initiated an assessment of the current challenges and barriers associated with this topic including: who determines evidence of benefit and what the standards for benefit should be; the expectations and limits of stakeholder responsibilities; the challenges of providing continued access to medicines in the case of second indications that are not approved,  the complexities of PTR in lower middle income countries (LMICs); the responsibilities of PTR in academic trials and specific issues involving implantable devices. The MRCT Center has conducted subject matter expert interviews, a legal landscape, and a literature review. The October 13^th Bioethics Collaborative focused on the ethical questions related to and application of the ethical principles for PTR.

A taskforce will convene in late 2023 to identify the necessary updates for the current framework that will offer practical solutions and answers for the continuing challenges.

Find out more about the MRCT Center’s work in Post-Trial Responsibilities.

The MRCT Center is committed to ensuring children benefit from clinical research, and that the youth voice is elevated and reflected in all aspects of clinical trials and product development. We continue to promote efforts that emphasize the importance of including children in clinical trials, harmonize processes, and improve access to medicines. Ethical and operational issues continue to challenge the conduct of pediatric clinical trials, and many countries do not have established regulatory frameworks for research in children. Thus, these efforts remain of critical importance to secure that safe and effective pediatric therapeutic products are available and accessible.

The FDA-funded Advancing International Pediatric Clinical Research webinar series, focused on critical aspects of pediatric clinical trials, continues. Webinars to date have covered an array of topics: (1) lessons learned from COVID-19 related to the initiation of pediatric clinical trials and the infrastructure needed to support the international pediatric clinical trial enterprise appropriately (October 2021); (2) elevating the pediatric voice in research from study design to assent (February 2022); (3) the cultural context of assent and consent encountered in the field (June 2022); and (4)  global regulatory cooperation, focused on building onto existing models to strengthen the global regulatory ecosystem for pediatric drug approval (November 2022).  The series will conclude in winter 2023 with the 5^th and final webinar that will coincide with the public launch of the pediatrics project and dissemination of associated deliverables.

In 2022, the MRCT Center added additional pediatric educational materials to the growing compendium of resources available to support young people thinking about becoming involved in clinical research.

Explore Promoting Global Clinical Research in Children.

Most participants want to receive research results, yet few receive them. In 2022, the MRCT Center released a web resource dedicated to the Return of Individual Research Results. The resource will help to lower the barrier to entry and promote adoption of a process for returning individual results to participants. In parallel, the MRCT Center has recently convened a small task force to help US and other clinical research and academic sites develop strategies for sharing aggregate study results with participants.

Find out more about the Return of Individual Results and Return of Aggregate Results project.

There is significant variability in ethical review and approval of decentralized and hybrid trials (collectively DCTs) that can lead to different approaches and often prolonged delays in approval. In partnership with Medable, a multi-stakeholder task force of ~20 people was convened to provide guidance and tools for sponsors, investigators and their study teams, and IRBs.

We hope that aligning expectations and processes, focusing on salient differences between DCTs and more “traditional trials,” and illuminating inherent ethical issues will help standardize and speed ethics review. A toolkit, IRB Oversight of Decentralized Clinical Trials, will be released in early 2023.

The Bioethics Collaborative of the MRCT Center brings together representatives from academia, patients and patient advocates, industry representatives, and the government to discuss ethical issues pertinent to multi-national clinical trials. Engaging individuals with diverse backgrounds and expertise together in conversation fosters informative and creative discussion. Conducted under Chatham House Rule, the Bioethics Collaborative is a unique opportunity for attendees to hear from people involved in different aspects of clinical research about their concerns, challenges, and successes. Collaboration among stakeholders is essential to effectively addressing these important and difficult issues.

The MRCT Center hosted four virtual meetings in 2022:

• February 3, 2022: Ethical Complexities with Human Challenge Trials
• April 5, 2022: Data Ownership, Reciprocity, and Research
• June 2, 2022: Sex and Gender in Clinical Research
• October 13, 2022: Post-Trial Responsibilities: Continued Access to Investigational Medicines and Devices

The MRCT Center is grateful to the following sponsors of the MRCT Center Bioethics Collaborative:

• Genentech, Inc.
• Eli Lilly & Co.
• Johnson & Johnson
• Merck, known as MSD outside of U.S. and Canada
• Pfizer Inc.
• Sanofi
• Takeda Pharmaceuticals International, Inc.

Recent publications related to meetings of the Bioethics Collaborative can be found here.

Find out more about the Bioethics Collaborative project

The Research, Development, and Regulatory Roundtable (R3) is an impartial forum to present and discuss pre-competitive issues in drug and device development, regulatory oversight of clinical trials, and human participant research. Meetings convene policymakers, legal counsel, academicians, industry representatives, and global regulators. Meetings of the R3 address one or two specific topics that are either directly related to policy or have legal implications for sponsors and investigators. Mark Barnes and David Peloquin of Ropes & Gray LLP, experts in this field of practice, summarize current issues and the pertinent rules and guidelines. The R3 provides a space for sponsors, researchers, and legislators to learn from one another and openly discuss the issues and difficulties they face; attendees are encouraged to ask questions. Additionally, the forum offers an opportunity to shape the direction of future policy and practice.

In 2022, the MRCT Center and Ropes & Gray LLP hosted four meetings of the R3:

• March 10, 2022: (1) “Investigator” Designation and (2) “Engagement” in Remote Clinical Research
• June 21, 2022: Recent Developments in the Trans-Atlantic Processing and Shipment of Personal Data for Research Purposes
• September 20, 2022: (1) Legal and Regulatory Perspectives on For-Profit Research Sites and (2) The Regulation of Research Involving Controlled Substances
• December 13, 2022: The Impact of International Privacy Laws on Research

Publications related to meetings of the R3 are found here.

The MRCT Center and Ropes & Gray LLP are grateful to the following sponsors of the R3:

• Advarra
• Amgen
• Dana-Farber Cancer Institute
• Genentech, Inc.
• International Society for Biological and Environmental Repositories
• Johnson & Johnson
• Mayo Clinic
• Merck, known as MSD outside of U.S. and Canada
• Sanofi
• Takeda Pharmaceuticals International, Inc.
• Vertex
• Washington University in St. Louis
• WCG IRB

Find out more about the Research, Development, and Regulatory Roundtable (R3) of the MRCT Center and Ropes & Gray LLP project.

The MRCT Center remains focused on advancing knowledge and access to clinical trials, while maintaining participant safety and data integrity as a top priority. In 2023, we will launch the expanded Clinical Research Glossary and training resources on health literacy. We will provide a set of tools to promote global clinical research in children and pursue the different roles and responsibilities of regulatory and health technology assessment agencies that can limit access to pediatric medicines. Our continued work in diversity, equity and inclusion will be focused on developing a framework for global diversity and inclusion and increasing access to clinical research for underrepresented communities including gender diverse people and people living with disabilities. We will convene a task force to explore post-trial responsibilities related to continued access to investigational drugs and devices after trial completion. We plan to continue our work on decentralized and hybrid clinical trials. Recognizing the need for the continuity of clinical research in the face of emergencies, we will work with stakeholders to understand and develop a framework for preparedness in clinical research. Finally, we will pursue cross-border data transfer, essential for scientific discovery and public health.

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