Missing in Action: Patient Perspective on Cancer Trial Goal

Maurie Markman, MD
Published: Sunday, Jan 14, 2018
Maurie Markman, MD

Maurie Markman, MD
There is a critically important subject associated with the clinical trial experience that has had inadequate discussion within the medical literature. That is, what is the role, or roles, of the patient beyond simply agreeing to serve as a research subject? This question is far from trivial or theoretical.

At the outset, let us consider that some clinical academic and bioethics experts as well as some governmental regulators have expressed the belief that clinical research and clinical care are fundamentally different endeavors. Such a belief apparently underlies decisions to conduct randomized placebo-controlled trials in order to observe an objectively measurable outcome in settings where others would strongly argue that available data clearly indicate the clinical value of an existing therapeutic strategy. However, the argument goes, if clinical research does not have to follow the ethical requirements of focusing on optimizing an individual patient’s chances for a favorable outcome—as would be the situation with clinical care—different rules would apply.

Vemurafenib Example Stands Out

A most distressing example of how a rigid focus on determining an unequivocal measurable outcome to a research question may seriously negatively influence individual patient welfare is provided by the regulatory decision several years ago to mandate a randomized phase III trial that compared the utility of a novel BRAF inhibitor, vemurafenib, with a control arm of dacarbazine, a widely recognized, highly toxic, and ineffective cytotoxic agent in the management of metastatic melanoma.1 Remarkably, this study was undertaken at a time when overwhelming clinical data existed regarding the favorable impact of vemurafenib on the natural history of this devastating condition, but where socalled “gold-standard,” randomized phase III trial data proving an overall survival (OS) impact did not yet exist.2

Did the regulators ever consider asking individuals with melanoma or their families, or perhaps patients with cancer as a group, what they believed to be the appropriate clinical trial design, based on the existing data, to permit the approval of vemurafenib for noninvestigative use in metastatic melanoma? And if not, why was it considered appropriate that this critical determination be made in the absence of such input?

Postapproval Study Dilemmas

A more recent example of the complete absence of a patientfocused perspective regarding clinical research is evident in discussions of regulatory requirements for postapproval studies, following a decision by the FDA to permit commercial sale of a given antineoplastic agent. In a commentary that appeared in the New England Journal of Medicine, the authors criticized the FDA and pharmaceutical companies for their failure to complete such studies in a timely manner.4
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