The Patient as Ultimate Outsourcer: Recent Initiatives in Patient-Focused Drug Development

Abstract

The growth of pharmaceutical outsourcing in recent decades is but one indication of the increasing complexity that has occurred within the scope of drug development. Advances in biomedical research alternatively inspire and confound manufacturers and developers— creating new opportunities, new problems, and new regulations. For physicians and allied health care professionals, these advances are frequently conceptualized under the rubric of “personalized medicine,” whereby new data and novel therapies challenge practitioners to target elements of disease particular to each patient. Within the Center for Drug Evaluation and Research (CDER) at the US Food and Drug Administration, there is an understanding of the heavy demands as well as rewards that characterize drug development in the twentyfirst century. CDER regularly meets with sponsors, applicants, and license holders to evince the safety, efficacy, and quality of new medical products. CDER also recently launched a new initiative known as “patient-focused drug development” to ensure the patient voice is actively included in drug development and regulation.

The Medical Community, Drug Developers, and Regulators: Unified by Patient Need

The ultimate goal of drug development is to meet the unmet medical needs of patients. Stakeholders of drug development adhere to good laboratory, clinical, and manufacturing practices precisely in recognition of an ultimate shared mission to bring safe, effective, and high-quality drugs to patients. Similarly, the Patient-Focused Drug Development initiative currently underway at the FDA Center for Drug Evaluation and Research (CDER) is a recognition of the importance of patient input.¹ Patient-Focused Drug Development at CDER is an initiative that uses patient input to leverage those data that correspond most directly with patient needs as they are experienced in the real world of the patient. It focuses on the need to ensure that sponsors measure things that are clinically meaningful to patients. It is worthwhile to note that the Food and Drug Administration Safety and Innovation Act of 2012 (FDASIA) Section 1137 stipulates that the perspectives of patients are to be considered in regulatory decisions, and the views of patients are to be solicited by the agency during the process of medical product development.

The great proliferation of biomedical information in recent decades has brought new levels of sophistication into research programs. But the technological sophistication that allows new and creative approaches to drug development also demands that one strategize—more critically and collaboratively than ever—to make the most judicious and efficient use of the data generated by the global biomedical enterprise. Judicious and efficient practices include the concept that data generation should be appropriate to patient needs. And in some instances, manufacturers of approved drugs and sponsors of new drug applications may be caught off guard by the patient-focused precepts that regulators are increasingly incorporating into drug review processes. For many, this is a new paradigm where patient-focused drug development works to place patient priorities and values within the regulatory framework. Just as health care professionals have moved from a doctor-knows-best ethos to a team approach to health care, regulatory efforts to incorporate patient perspectives (especially as it relates to clinically meaningful outcomes) into drug development are consistent with cross-sector trends and strategies that, in comparison to those of previous decades, are far more collaborative.

In many ways, CDER’s Patient-Focused Drug Development is an initiative that will assist the industry to be more sophisticated in using cutting-edge technologies efficiently in drug discovery. At the same time, the initiative resonates with the earliest constructs of the patient-physician dyad and the age of materia medica. All stakeholders in drug development should give important consideration to the views of patients, as patient input promises to affect not only drug development programs in general, but also the practices of drug prescribers, the language of drug regulators, and ultimately, the labeling of drug products. The patient perspective will thus affect profound dimensions of development, and new drug products will better conform to the needs—and the risks—that patients will be empowered to prioritize for themselves.

Patient Participation in the CDER Mission before FDASIA

The earliest desire by patients to be involved in drug development dates back to the 1980s when one can recall the images of patient communities confronting the HIV/AIDS outbreak. These advocates were quite effective in marshaling stakeholder involvement—and particularly, regulatory involvement—to address new and urgent medical needs.² Patients facing other serious diseases—most notably, in the oncology arena—have similarly advocated for access to novel drugs in recent years, and programs of expedited review and expanded access have consequently been strengthened within CDER. For a decade, the voice of the patient has been formally and incrementally incorporated into regulatory decision making, as patient representatives have served—today, with voting privileges— on the advisory committees that convene in anticipation of new drug approval decisions.³

In addition to patient groups representing relatively high-visibility diseases such as cancer and AIDS, CDER has elicited input from advocacy organizations and families of patients who have serious, and often less-well understood, rare diseases.⁴ Drug development for serious disease of any nature has numerous challenges, among which is the definition of clinically meaningful endpoints that are functionally relevant to the patient experience of disease progression. Patients with rare diseases—who collectively number about 7,000,000 in the US—have organized into well-educated and sophisticated groups who continue to provide important insights into the proper design of trials in particularly challenging disease areas.

Collaborations among patient organizations, industry, academics and other professionals have grown markedly in recent years to develop new tools for the design and execution of better clinical trials. Multiple types of tools are in development, requiring expertise from many specialized areas in medicine and manufacturing. And one type of drug development tool that has particularly engaged patients is the patient-reported outcome tool. Regulators and developers have been challenged in making sure that all clinical assessment outcome tools are properly qualified for use in defined contexts, and this challenge includes the development and qualification of patient-reported outcome tools.⁵ The FDA has developed a guidance document that provides industry with the agency’s thoughts regarding patientreported outcomes in clinical trials.⁶

Patient Participation in the Age of FDASIA

CDER is currently taking concrete steps to bring the patient perspective into the regulatory environment, as required under FDASIA, beyond the mechanisms outlined above. Along with the Center for Biologics Evaluation and Research (CBER), CDER has committed to convene at least 20 meetings on specific disease areas before 2017. The agency, after collecting thousands of comments from interested parties, selected 16 disease areas around which to organize patient meetings.⁷ The disease areas chosen for the Patient-Focused Drug Development meetings were selected to reflect the broad disease categories that comprise the work within CBER and CDER, with emphasis on chronic, symptomatic disorders that compromise patient function in daily activities.

The disease areas underlying the initiative generally have few or no therapies that directly affect how the patient feels or functions; about half of the areas represent rare diseases. These diseases may challenge clinical trial developers to design endpoints and other trial elements reflecting important aspects of disease. The input that patients are uniquely positioned to provide is crucial to the success of the Patient- Focused Drug Development initiative, and the meetings that have already been held at the agency campus have been recorded and presented in reports that are freely available.⁸

Input provided so far by patients through the Patient-Focused Drug Development initiative has been valuable to FDA staff conducting benefit-risk assessments for products under review. A draft guidance concerning the development of drug products for chronic fatigue syndrome/myalgic encephalomyelitis, released this spring by CDER, referenced the patient meeting for the condition that had been held under the Patient-Focused Drug Development initiative.⁹ As a mechanism for building relationships between the agency and patient communities, the initiative may feed into other avenues for patient input. Recently, the Parent Project Muscular Dystrophy group submitted a draft guidance to the agency that discusses elements of trial design and benefit-risk for consideration in the development of therapies for Duchenne’s.¹⁰

Conclusion

The improvements that stakeholders need to impart into drug development programs encompass a number of goals, including more efficient trial design, better defined endpoint assessment, and more reliable drug development tools. Such improvements will often be dependent on a more fully elaborated understanding of the realities and needs of patients as they experience serious disease over time. As the FDA continues to support patient-focused drug development, patient values and experiences with disease will be better known not only to regulators, but also to stakeholders in manufacturing and development. We encourage stakeholders to consult the reports that CDER provides regarding our meetings with patient communities¹¹ and to bear the patient perspective in mind in regard to regulatory issues. “Patient-focused” drug development is fundamentally a practical initiative, around which all stakeholders can engage in meaningful discourse and organize drug development efforts most effectively.

References

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9. US Food and Drug Administration. FDA workshop on drug development for chronic fatigue syndrome (CFS) and myalgic encephalomyelitis (ME). Available at: http://www.fda.gov/Drugs/NewsEvents/ucm369563. htm. Accessed August 25, 2014.
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John J. Whyte, MD, MPH, is currently the Director of Professional Affairs and Stakeholder Engagement at the Center for Drugs Evaluation and Research at the US Food and Drug Administration. In this role, Dr. Whyte works with health care professionals, patients, patient advocates, and others involved in the use of medicines. His office provides them with a focal point for advocacy, enhanced two-way communication, and collaboration, and assists them in navigating the FDA on issues concerning drug development, review, and drug safety. He also oversees the Safe Use program and supports the ongoing partnerships and activities under the Safe Use Initiative.
Previously, Dr. Whyte served as the Chief Medical Expert and Vice President, Health and Medical Education at Discovery Channel, the leading non-fiction television network. In this role, Dr. Whyte developed, designed, and delivered educational programming that appeals to both a medical and lay audience. This included television shows as well as online content.
Prior to Discovery, Dr. Whyte was in the Immediate Office of the Director at the Agency for Healthcare Research Quality. He served as Medical Advisor/Director of the Council on Private Sector Initiatives to Improve the Safety, Security, and Quality of Healthcare. Prior to this assignment, Dr. Whyte was the Acting Director, Division of Medical Items and Devices in the Coverage and Analysis Group in the Centers for Medicare & Medicaid Services (CMS). CMS is the federal agency responsible for administering the Medicare and Medicaid programs. In his role at CMS, Dr. Whyte made recommendations as to whether or not the Medicare program should pay for certain procedures, equipment, or services. His division was responsible for durable medical equipment, orthotics/prosthetics, drugs/ biologics/therapeutics, medical items, laboratory tests, and non-implantable devices. As Division Director as well as Medical Officer/Senior Advisor, Dr. Whyte was responsible for more national coverage decisions than any other CMS staff.
Dr. Whyte is a board-certified internist. He completed an internal medicine residency at Duke University Medical Center as well as earned a Masters of Public Health (MPH) in Health Policy and Management at Harvard University School of Public Health. Prior to arriving in Washington, Dr. Whyte was a health services research fellow at Stanford and attending physician in the Department of Medicine. He has written extensively in the medical and lay press on health policy issues. His book, Is This Normal? The Essential Guide to Middle Age and Beyond, has won numerous awards. His most recent book, AARP New American Diet: Lose Weight, Live Longer, is a national best-seller.