By John Whyte, M.D., WebMD, and James Gillespie, Ph.D., Saint Mary’s College
We are in the era of value-based, patient-centric precision medicine. Today’s patient engagement movement is born of patients who ever more frequently demand to be active participants and final decision makers in their healthcare. Instead of having providers just perfunctorily listen to their values, patients want those values to be genuinely heard and prevail in decision-making. This is particularly important given that medical decisions are complex and multidimensional, involving significant considerations of economic costs, probability of survival, and quality of life.
Consistent with this, many clinical research organizations (CROs) and biopharmaceutical companies are attempting to integrate patient-centricity into every phase of drug discovery, development, and deployment. Patient-centric drug development is taking center stage as clinicians and patients try to collaborate and provide input on issues related to safety and effectiveness, powered by increasingly sophisticated data analytics.1 And because its essence is empowering patients to first comprehensively understand their array of treatment options and then to make informed decisions based on their own individual values and preferences, precision medicine fits hand in glove with patient-centricity.
In the first part of this two-part article, we examine the implications the transition to value-based, patient-centric, precision medicine has for drug discovery, development, and deployment, particularly for clinical trials.
Problems With One Size Fits All And Trial And Error
Traditional clinical trials are expensive, lengthy, and resource intensive. Although patients are different in numerous ways, treatment protocols are generally based on a relatively select group of patients, and clinical studies are often constructed to assess efficacy (i.e., results of the intervention under ideal circumstances) rather than effectiveness (i.e., results under “real-world” clinical settings). The classic controlled, scientific design of clinical trials is precisely the factor that may reduce the applicability of the results to patients outside of the carefully selected study group. Clinical trial populations often tend to be healthier, younger, and less demographically diverse, so this setup is not geared to gain data to support individualized treatment plans. As a result, the current system can be rife with false negatives, false positives, overmedication, unnecessary treatments, and other errors/inefficiencies for many patients. It may be difficult to determine if the results are truly generalizable as well as whether the outcome measures are clinically meaningful to patients.
Because our current treatment protocols are mostly based on a relatively narrow group of patients, drugs that perform well in clinical trials often underperform in medical practice, failing to improve outcomes or symptoms among a significant portion of patients. Clinicians increasingly recognize that the “one size fits all” strategy for treating patients does not perform well in cases where individual variability is needed for designing an optimal treatment regimen. The trial and error approach to medicine is not cost efficient because several of the most prominent drugs only work on one-third to one-half of patients. Thus, many patients are subjected to the cost, inconvenience, side effects, and potential adverse reactions of taking medicine that will have little to no clinical benefit. Precision medicine can remove or at least curtail the present tendency to develop individual diagnoses and treatments based on general results that lead to guesswork and substantial variability in outcomes.
Precision Medicine And Patient-Centricity
What is precision medicine? Contrary to what many patients, physicians, and even policy makers think, precision medicine does not literally mean that unique products/treatments (e.g., drugs, medical devices) are designed and created for each individual. That would be impractical clinically and prohibitively expensive. Instead, precision medicine refers to classifying patients into subpopulations based on differences in demographics, genetics, prognosis, susceptibility, treatment response, and other essential elements. Precision medicine combines elements of bioinformatics, biomarker research, genomics, epigenomics, nutrigenomics, pharmacogenomics, and proteomics, along with considerations involving environment, lifestyle, and traditional medical data. It allows clinicians to target preventive and therapeutic interventions for patients most likely to benefit, while sparing others the expense, inconvenience, and side effects. Patients often consider precision medicine to be “personalized medicine,” although that is a misnomer.
Patients, payers, government, patient advocates, and other stakeholders increasingly demand proof of effectiveness. Given the current shift to high-deductible insurance plans, being patient-centric and value-based must now also include providing the comparative costs attached to different treatment options. Precision medicine holds the potential to improve the cost, speed, and success rate of clinical trials, which can translate into better healthcare value. The typical R&D cycle lasts over 10 years, and precision medicine can subtract weeks and even months from this time frame. Implementing precision medicine early in the process can enhance identification of new drug targets, benefit decision-making, and improve both effectiveness and efficiency. Even with expensive individual therapy, there can be overall cost savings because drugs are given to patients only where they will be effective. In terms of the R&D process, the advantages of precision medicine are numerous and include more accurate identification of new drug targets, increased clarity on the ideal patient profile, more targeted trials requiring smaller statistically valid pools of patients, increased probability of regulatory approval, higher certainty for formulary adoption of medicines and reimbursement, and longer market exclusivity.
Precision medicine is a transformational analytical tool that is gaining momentum. It leverages advanced analytics, Big Data, deep learning, and statistical models, allowing clinicians to comprehensively explore the composition of an individual patient’s distinct ailment and demographic and genetic factors. Personalization is indeed the future of healthcare, and the percentage of drug pipelines including precision-medicine-based targeted therapies continues to increase. And to what indications is it most applicable? Because of the heterogenic component of cancer, as well as issues related to treatment cost and patient mortality, oncology is the primary area for precision medicine. However, the use of precision medicine, as well as the supporting use of biomarkers and companion diagnostics, is now actively moving from oncology to a variety of non-oncological therapeutic areas (e.g., cardiovascular, central nervous system, and infectious diseases).
Patient-centric, precision-medicine-oriented healthcare needs to give rise to patient-centric, precision-medicine-oriented clinical trials. Instead of being viewed as mere data points, clinical trial patients are increasingly seen as core and integral to the process. There is an art and science to communicating with patients, and true patient-centricity requires an organizational mind shift by executive sponsors, protocol designers, site leadership, and operations to prioritize patient goals. Patient-centricity in clinical trials starts with understanding the person’s reasons for participating and showing sensitivity to their goals, interests, and motivations. It must strive to measure what is clinically meaningful to patients as outcome measures. Clinical trials are starting to have more two-way communications between patients and providers/investigators, as well as between patients and CROs/biopharmaceutical companies. Patient input is sought on informed consent forms, protocols, and trial designs.
In conjunction with patient-centricity, precision medicine helps empower patients to make highly consequential and intensely personal healthcare decisions, whether in clinical trials or in non-trial care settings. One could argue that precision medicine is the ultimate case of patient-centricity. Precision medicine brings into focus the idea that patient outcomes matter most. Customized treatments are the final step in putting patients at the center of clinical trial operations, and precision medicine, in combination with patient-centricity, offers the potential to make pharmaceutical companies and CROs truly trusted partners in the clinical trial process. This new approach will require life sciences companies to provide a high-quality, personalized patient experience and to drive learning, continuous improvement, informed decisions, and optimal outcomes while recognizing that patients are not a monolithic entity.
Part 2 of this two-part article explores precision medicine in more depth, explains how real-world data (and data from other sources) underpins the ability to develop and deliver specific medicines for specific patients, and considers how the twin dynamics of patient-centricity and precision medicine will require the redesign and transformation of processes for converting molecules to medicines for patients.
About the Authors:
John Whyte, M.D., is currently the chief medical officer at WebMD. In this role, he leads efforts to develop and expand strategic partnerships that create meaningful change around important and timely public health issues. Prior to WebMD, Whyte served as the director of professional affairs and stakeholder engagement at the FDA’s Center for Drugs Evaluation and Research, where he worked with healthcare professionals, patients, and patient advocates to provide them with a focal point for advocacy, enhanced two-way communication, and collaboration.
James Gillespie, Ph.D., is a faculty member in the Department of Business and Economics at Saint Mary’s College, where he focuses on international management and new ventures. His experience includes the Center for Healthcare Innovation in Chicago, the Stanford University School of Medicine’s Clinical Excellence Research Center, the Yale University School of Medicine’s Center for Digital Health & Innovation, and Chief Strategy Officer at MyKaren. Gillespie’s education includes Carnegie Mellon University, Harvard University, Massachusetts Institute of Technology, Northwestern University, and Princeton University.