Fifteen Eighty Four

Randomized controlled trials (RCTs) dominate clinical research. Among many research designs, RCTs are often considered the gold standard—the most credible and respected form of evidence. In fact, authors of systematic reviews frequently exclude studies that use other methods. But is this preference always justified?

In many cases, yes. Carefully designed RCTs test the efficacy of new treatments under tightly controlled conditions, using highly selected patient populations and standardized protocols. They are expensive, time-consuming, and difficult to conduct. Yet, they remain the most common study design listed on clinicaltrials.gov, the U.S. registry for clinical research—outnumbering observational studies by four to one.

But should they?

RCTs are undeniably valuable. If a treatment doesn’t work in ideal conditions, it’s unlikely to succeed in the messy, complex reality of everyday clinical practice. Still, observational studies—conducted in real-world settings—ask a different but equally important question: Does this treatment help people like me, in circumstances like mine?

Despite their relevance, the impact of observational studies is greatly outpaced by RCTs. This isn’t because observational studies are less important, but because RCTs absorb all of the attention. As a result, we miss opportunities to understand how treatments perform in the real-world settings where most people actually receive care. This is not a call to abandon RCTs. Rather, it’s an appeal for balance. Both experimental and observational studies offer essential insights, and neither alone is sufficient. If we want healthcare to improve for everyone—not just ideal study subjects—we need to support a wider range of rigorous, patient-centered research approaches. If research continues to prioritize experimental purity over practical relevance, we risk widening the gap between medical knowledge and clinical practice. Policymakers, academic institutions, and funding agencies have a role to play in reshaping priorities.

In our new book, Rethinking Clinical Research: Methodology and Ethics, we explore the strengths and limitations of different research methods. We trace the arc of clinical research—from how questions are framed, to how findings are disseminated, adopted, or overlooked. Along the way, we challenge long-standing assumptions about study design, outcome measures, and what counts as meaningful evidence.

Consider this: clinical trials often rely on proxy endpoints—such as lab values or imaging results—that may not reflect what matters most to patients. We propose that healthcare research should focus on two core outcomes: living longer and maintaining a high quality of life. For example, heart disease matters because it can lead to early death and can diminish quality of life by limiting physical function and causing distressing symptoms. Measuring what patients value, such as their ability to function, feel well, and participate in daily life, should be a top priority.

We also address a paradox of modern science: while data production is growing exponentially, staying current is harder than ever. Peer review—the system designed to ensure scientific quality—is under increasing pressure. In Rethinking Clinical Research, we examine how this system can be improved or reimagined for today’s needs.

Our book is written for healthcare professionals, students, and thoughtful readers from any background. To spark discussion, we offer four case studies: statins for high cholesterol, antidepressants, proton pump inhibitors for acid reflux, and mammography for breast cancer screening. These topics were chosen because they are widely accepted and often viewed as uncontroversial. Yet a closer look reveals important, unresolved questions about their safety, effectiveness, and appropriate use.  Our goal in offering these case studies of accepted practices is to provoke discussion and encourage new thinking about study designs.

Clinical research is not only a technical pursuit—it is a moral one. The studies we prioritize reflect our values, and too often, those values overlook the messy realities of patients’ lives. Rethinking clinical research means asking better questions, valuing lived experience, and designing studies that serve both science and society.

Ultimately, the purpose of clinical research is to improve lives, not just to publish findings. When we evaluate treatments, the outcomes that matter most to patients must take center stage. Our hope is that Rethinking Clinical Research will inspire researchers, funders, and clinicians to adopt a more patient-focused, context-aware approach to evidence generation.

Title: Rethinking Clinical Research

ISBN: 9781009391726

Author: Karen B. Schmaling and Robert M. Kaplan