Patients’ Voices Largely Absent From FDA Reviews of New Cancer Drugs

More and more clinical trials of cancer drugs involve assessments of patients’ views on how treatments are affecting them. The US Food and Drug Administration (FDA) encourages the gathering and reporting of these patient-reported outcomes (PROs), which offer insight into the patient experience without biased interpretation by investigators. Still, PROs for cancer drugs are frequently absent from marketing approval requests submitted to the FDA, or they are inadequate. Recent studies have found that the FDA approves many novel cancer drugs without PROs, so these medications reach the market without patients’ perspectives on how these products influenced their quality of life.

A study presented at the American Society of Clinical Oncology’s 2023 annual meeting by investigators at Howard University in Washington, DC, revealed that less than half of 420 pivotal trials leading to FDA cancer drug approvals from 2006 to 2022 included PRO assessments.¹ Another study, published in 2023 in Supportive Care in Cancer,² showed that of 59 unique cancer drugs approved from 2013 to 2022 via the FDA’s accelerated approval pathway, only 59% included PRO assessments in the clinical trials. The investigators concluded that “PRO measurements are inconsistently utilized in trials leading to initial accelerated approvals of oncology drugs, and there seems to be a lack of harmonization of different PRO measurement tools across trials.”

In another study, investigators who reviewed transcripts from 27 meetings of the FDA’s Oncology Drugs Advisory Committee (ODAC) from 2016 to 2021 found that PRO-related topics were mentioned in only 12, according to a report in JCO Oncology Practice.³ Of those, ODAC reviewers were satisfied with PRO assessments in only 2.

“During ODAC meetings, committee members and FDA reviewers expressed frustration at the lack of PROs captured in clinical trials for cancer treatments,” authors Ari Gnanasakthy, MBA, MS, and colleagues concluded. “Less than half of evidence packages for cancer treatments submitted for FDA review included PROs. Even when PROs were included in evidence packages, the PROs were rarely deemed adequate for benefit-risk assessments.”

They added: “Lack of credible PRO data in oncology clinical trials prevents regulators from making comprehensive and accurate assessments of the benefits and risks of new cancer treatments. Clinicians and patients, therefore, are forced to choose among treatment options without understanding the experiences of patients who were treated with these options.”

Influence on Formularies

Lack of PROs could adversely affect decisions about which medications are placed on health plan formularies and thus covered by insurance. A survey of health plan representatives (90% pharmacists, 56% pharmacy administrators) found that 78% of the 106 respondents thought PRO evidence is useful for providing additional context for safety of oncology therapies. In addition, 47% suggested that formulary reviews would be at least somewhat influenced by a lack of PRO evidence from oncology clinical trials.

“US payers view PRO evidence from both clinical trials and real-world studies as useful for supplementing traditional clinical trial data when making oncology formulary decisions and for refining treatment pathways and care delivery models,” investigators Gary Oderda, PharmD, MPH, and coauthors concluded in a 2022 paper in the Journal of Managed Care & Specialty Pharmacy.⁴ “Manufacturers of oncology therapies should collect and consider leveraging PRO evidence from both settings when engaging with US payers.”

Primacy of Objective Data

Although PROs, which are subjective, can provide FDA reviewers with additional information to consider, objective data must be the foundation for evaluating a drug except in cases in which a drug’s effectiveness can only be evaluated using PROs, said Peter Lurie, MD, MPH, President and Executive Director at the Center for Science in the Public Interest in Washington, DC, and former Associate Commissioner for Public Health Strategy and Analysis at the FDA.

For example, in clinical trials of pain drugs, investigators have to rely on PROs to gauge effectiveness because changes in pain perception in response to treatment are subjective. This is not the case with diseases such as cancer for which objective measures are available, Dr Lurie said. Those measures, and not patient opinion, must provide the basis for approval. Cancer drugs “should not be coming onto the market because the majority of patients think the drugs work for them,” he said.

Dr Lurie asserted, “Encouraging assessment of PROs is definitely a good idea; making it a required part of the primary assessment of safety and efficacy probably is not.”

The American Society of Clinical Oncology said in an emailed statement that it “recommends that trialists consider including attributes of accessible and equitable research, such as patient-reported outcomes, in the design and conduct of all clinical trials, as understanding how patients are affected by a therapy is paramount.”

This article originally appeared on Renal and Urology News