Informed Consent for Early Phase Cancer Clinical Trials – Helping Patients to Separate Hope and Hype

Abstract

Informed consent for clinical trial participation is the bedrock of Good Clinical Practice, the “bible” for clinical research conduct across the world. The importance of informed consent came out of a history of unethical experimentation on humans (e.g. The Tuskegee Syphilis Experiment) and a determination for the medical research community to ensure that participants are adequately informed of risks and beenfits.

Cancer is a leading cause of death, and there is extensive interest in developing novel therapeutics. Early phase cancer clinical trials, the mandatory first step in drug development, have been controversial in the last two decades. In an early phase trial, scientific findings are translated into the clinic, and represent hope for patients who have exhausted standard therapies. Often the starting dose may be below levels expected for therapeutic activity and the hope for activity will vary substantially depending on the patient-trial combination.

Recent years has seen an increasingly assertive and confident cancer research community given successes with blockbuster drugs such as pembrolizumab and better knowledge of molecular matching with highly actionable targets such as ALK, NTRK and RET. Nevertheless, separating “hope” in the small minority of trials which may offer substantial benefit, from “hype”, the majority of trials which offer either no benefit, toxicity, or a small benefit is a key task in obtaining informed consent for early phase trials.

It is well known that informed consent documents are unreadable and inadequate, clinician-patient conversations are incomplete and use inappropriate language. At the same time, the population of patients considering early phase trials are vulnerable given they are facing a terminal diagnosis.

This PhD examines current knowledge, and a 4 year program of work at the Royal Marsden Drug Development Unit to understand and improved informed consent for early phase cancer trials.