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Since the article on Therapeutic Misconception (TM) and Phase 1 cancer trials in Voices in 2013, little has changed. There are still bioethical concerns about the validity of informed consult in these research studies. Although the informed consent process should differentiate between individualized clinical care from scientific research, patients often conflate the two. TM describes the failure of research subjects to appreciate the boundaries between trial participation, where data is generalizable, from treatment aimed at providing individual benefit.
Clinical research in oncology is vital to evaluate the efficacy of existing and novel treatment approaches, with the number of active cancer trials in the US estimated to be about 12,500 in 2022. There are, however, several ethical issues to consider in Phase 1 oncology trials. A consequentialist position suggests these trials are ethical regarding the commitment to gaining knowledge, as they provide necessary information about dose and toxicity. Does recruiting patients with advanced malignancies to study dose and toxicity without primary intent to treat stand on solid moral grounding? Given the small therapeutic value, toxicity risks, and high prevalence of TM, there is still debate about whether these trials are valuable for patients and whether researchers are promoting false beliefs to advance their agenda. To ensure valid informed consent, I contend that the researcher/oncologist must anticipate the TM and “Tell it Like It Is” concerning the likelihood of true therapeutic benefit.
It is important to convey whether these trials provide any individual response. Most patients with advanced cancer enroll with hopes for positive treatment outcomes and not for altruistic reasons. Major cancer centers advertise in newspapers and on their websites that clinical trials are part of the treatment options available to patients, all factors that lead to a subject conflating clinical care with research. In a study done at Emory University in subjects enrolled in phase 1 trials, 68.4% of subjects interviewed had a TM. Most patients anticipated therapeutic improvement, such as a reduction in tumor size. However, older data report a tumor response rate of 4-6%. With newer targeted therapies and precision medicine, response rates may be better than ten years ago; recent studies of genomic biomarkers used for patient selection suggest response rates of higher than 20%. But for many patient subjects, these are not realistic expectations.
From the justice perspective, it is crucial to balance the desire to advance scientific knowledge, the possible small benefits of therapy, and the potential harms. Excluding patients with advanced malignancies would not be fair, as they are autonomous individuals and should be able to choose. However, patients should only be exposed to the potential harm of these trials if they understand the risks and benefits. A prospective study of patients with advanced cancer found that clinical trial participation was associated with aggressive treatment at the end of life, often coupled with poor outcomes for patients and family members. I contend that the researcher/oncologist must anticipate the TM and “Tell it Like It Is” concerning the likelihood of true therapeutic benefit, toxicity, and options for alternative approaches. The discussion should be interactive, balanced, and realistic. For consent to be valid, the subject must have the capacity to make autonomous decisions and understand the purpose of the research and the responsibilities of a participant. Providing valid consent remains challenging, but patients with advanced cancer should only make these decisions after being presented with honest disclosure. Scientists in the clinical setting must recognize that the interests of the researcher and patient may not be fully aligned, given potential conflicts of interest regarding career advancement and financial rewards through research. If there is a preceding primary relationship between the oncologist/researcher and the patient, beneficence should promote actions that minimize harm and maximize the patient's welfare.
What hasn't changed is that the oncologist-researcher must focus on the elephant in the room, advanced cancer, and not avoid challenging encounters. Patients as subjects desperately hope for a positive clinical response, but they and their families need to know whether they can expect any meaningful improvement. For some patients, continuing “treatment” adds meaning to their lives. After these conversations, patients may decide to participate for altruistic reasons or understanding that there might be a small clinical response, which may be more likely now, given advances in cancer therapeutics. The patient-subject can then confidently make a fully informed decision with valid consent if the researcher is transparent.
Having lived in both roles as a physician studying bioethics and a patient with cancer, it is clear that we deserve to Hear It Like It Is.