Every time you take a prescription medication, you are impacted by a clinical trial. From insulin to ibuprofen, every one of the more than 20,000 prescription medications currently on the market in the United States underwent controlled testing in human subjects prior to receiving approval by the U.S. Food and Drug Administration (FDA). The intent of clinical trials is to demonstrate the safety and effectiveness of a drug, yet poor study design may impede this process. This article highlights the need for the power of patient voice in the clinical design process.
Current clinical trial design
Most pharmaceutical manufacturers utilize the gold standard of clinical trial design: randomized, controlled trials (RCTs) executed in four phases. Any protocols used must be approved by the FDA under an Investigational New Drug Application (IND) prior to clinical trial execution. Patients meeting defined criteria for their disease state are randomly assigned to receive the investigational product (IP). Neither the patient nor the researcher administering the drug are to know which IP was provided. Safety and dosage are determined in a small group of people over months (Phase 1) while efficacy and side effects are determined in a large group over two years (Phase 2), larger groups over 1-4 years (Phase 3) and several thousand volunteers in post-market approval (Phase 4). Phase 1 through Phase 3 clinical trial data are submitted to the FDA as part of a New Drug Application (NDA). Any pharmaceutical manufacturer in the United States is required by the 1938 U.S. Food, Drug and Cosmetic Act and 1962 Drug Amendments to submit safety data including adequate and controlled studies in humans to receive market approval.
While patients are critical for clinical trial execution, they are often not included in the study design protocol. Medical professionals and scientific researchers write and execute most protocols. As such, many clinical trials do not include or may not significantly impact their target patient population. Protocol complexity — from Phase 1 through Phase 4 — has increased significantly in the past 10 years, resulting in costly trials with far fewer patients than intended. Complex study designs can deter physicians from referring their patients to trials, patients often may not enroll due to geographical proximity to study sites, while those enrolled often drop-out due to extensive protocol demands.
The power of patient voice
Incorporating patient voice in protocol design can help eliminate many of these roadblocks, improving the efficiency, impact, cost and time to completion of clinical trials. Pharmaceutical companies that have used systems that provide patient feedback prior to protocol execution saw a reduction in the number of protocol amendments and administrative burden. Increased patient involvement also improved clinical trial enrollment and retention in the United Kingdom (UK).
Lessons learned from these UK trials and patient engagement with HIV/AIDS in the 1980s led the FDA to now require patient input both before, during, and after clinical trials. The FDA holds public patient focused drug development meetings (PFDD) to foster dialogue on a particular disease per the 2012 reauthorization of the Prescription Drug User Fee Act (PDUFA). The 2016 21st Century Cures Act and 2017 Food and Drug Administration Reauthorization Act encourage the incorporation of patient experience data to be included with all new drug applications. Guidance documents on how to collect and incorporate patient experience data in drug development are also underway. One such guidance states patients have a direct stake in drug development and as such clinical trials should incorporate elements critical to them.
The increased patient-centric focus in drug development by the FDA is highly encouraging and expected to become more mainstream and legislated.
Several industry leaders also support the change. Thomas P. Sellers, a prostate cancer survivor and Senior Director of Patient Advocacy and Corporate Philanthropy for Takeda Oncology, said having patients embedded in the process from the outset is critical for clinical trial outcomes at his company.
MEI Pharma leveraged patient experience from previous clinical trials to apply intermittent instead of fixed dosing regimens for their ME-401 drug candidate for treatment of B-cell malignancies. Dr. Richard Ghalie, Senior Vice President for Clinical Development at MEI Pharma, believes adjusted dosing regimens help put patients at the heart of clinical trials.
Crowdsourcing can also harness patient voice to shape clinical trial design. Online platforms from companies such as Transparency Life Sciences enable qualified stakeholders (patients, caregivers, clinicians) to collaborate on the construction of a clinical protocol. No physical limitations exist for such online applications, maximizing potential users, shortening the time to protocol completion and deceasing overall cost. Such tools can also provide the fit-for-purpose clinical outcome assessments required by the new FDA patient experience guidance.
Dr. Matthew Galsy, Director of Genitourinary Medical Oncology at Tisch Cancer Institute at Mount Sinai School of Medicine in New York, used a crowdsourcing platform to develop a clinical trial for metformin in men with rising prostate-specific antigen after localized treatment for prostate cancer. He notes the immense benefit of shaping a clinical trial by the united, inspired, and logical thoughts provided by the crowd.
Taken together, clinical trials provide a critical risk-benefit assessment of new drugs in humans prior to their release to the public. Regulatory agencies such as the FDA now encourage patients to shape the design of these trials to ensure the most effective, efficient and impactful outcome. Furthermore, novel technology, including software-enabled systems, can advance understanding of a life-altering therapeutic by facilitating the rapid and efficient analysis of results, changing the way we think about future clinical trial design.
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