Trial Innovations: Potential Impact on Access to Experimental Treatments

By: Jane Reese Coulbourne, MS ChE

As Right to Try efforts gain visibility and patients increasingly demand earlier and greater access to experimental medicines, regulators are working with study sponsors, academic centers and patients on ways to facilitate broader access to clinical trials and simultaneously afford individual patients access to information about their diseases and potentially more effective treatments sooner.

Janet Woodcock, MD, Director of the US Food and Drug Administration (FDA) Center for Drug Evaluation Research (CDER),  and Lisa M. LaVange, PhD, Director of CEDER’s Office of Biostatistics, provide examples of these newer trial designs in the July 6, 2017 New England Journal of Medicine article, Master Protocols to Study Multiple Therapies, Multiple Diseases, or Both .“We need to find ways to answer more questions, more efficiently and in less time,” argue Drs. Woodcock and LaVange., We couldn’t agree more.  Their detailed examples of methodologic innovation explain how these trials have been designed to evaluate multiple targeted therapies in a single protocol open at many institutions, addressing challenges in recruiting patients with rare diseases, and sometimes rare genetic subtypes of a disease.

Potential access to multiple experimental medicines can be very attractive to a patient who has exhausted all standard-of-care treatments. For example, the I-SPY 2 trial includes response-adaptive randomization, allowing a patient who has met the trial entry criteria to receive an experimental treatment regimen and, if responsive, to remain on that treatment, or  if non-responsive, to move on to yet another experimental treatment regimen.

Including larger numbers of patients, with different types of disease, across a single trial addresses access challenges for patients as well as recruitment challenges for researchers. The LUNG-MAP protocol classifies patients into genetic subgroups. The design also includes participants whose biomarker signatures do not fall into any of the defined subgroups:  these patients are not eliminated from the protocol but are instead assigned to the no-match subgroup in which they receive an experimental targeted therapy and are evaluated against the standard of care in the five substudies, allowing more screened patients to participate.

Drs. Woodcock and LaVange share key learnings through these examples: “By taking advantage of coordinated data collection across multiple trials, master protocols can enhance other initiatives.”  While not specifically discussed by the authors, pre-approval access (PAA) offers yet another setting for the systematic collection of data.  Leveraging a trial network with an established infrastructure can expand our knowledge of new therapies.  Data from PAA patients who are potentially sicker and ineligible for clinical trials can provide evidence of how real world patients will respond to medicines once approved by a regulatory authority.

Going forward, finding ways to ethically provide access to more patients and simultaneously capture more data from each patient is a strategic win-win for all patients.

** Disclosures: Reese-Coulbourne was treated in a Phase II clinical trial for advanced breast cancer, serves as a member of the I-SPY 2 Independent Agents Selection Committee (IASC), and was the founding Executive Director of the Reagan-Udall Foundation for the FDA. She is currently a senior consultant at MK&A and a member of the New York University School of Medicine Working Group on Compassionate Use and Pre-approval Access, focusing on ethical access program design and data collection.

 Additional Resources:

  • Pre-approval access programs and real world data collection: click below to download MK&A’s latest FAQ

To learn more about adaptive trial design and pre-approval access, please contact Jane at

About the Author:

Jane Reese Coulbourne, MS ChE

Jane is a senior consultant at MK&A.  Jane brings comprehensive knowledge of evolving regulatory requirements and sensitivity to patients and sponsors’ needed in the conception and design of pre-approval drug access programs. She has helped shape policy and practice in this new paradigm of patient advocacy for early access to experimental treatments.

Most recently, Jane was the founding executive director of the Reagan-Udall Foundation for the FDA. Prior to that, she was an advisor to Dr. Richard Klausner, director of the National Cancer Institute. She served as executive vice president of the National Breast Cancer Coalition and as the board chair of the Lung Cancer Alliance.

Jane holds an MS in chemical engineering from the University of Virginia.

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