Oncologic drug development needs to place a greater focus on the patient, according to a commentary in the current issue of the New England Journal of Medicine. Even though the US Food and Drug Administration (FDA) has begun taking steps to include the patient perspective in drug development, there is still much to be done.
In his commentary, Ethan Basch, MD, associate professor of medicine and director of the cancer outcomes research program at the Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, notes that the first question patients ask about a new chemotherapy regimen is, "How will it make me feel?"
They also want to know how patients similar to them "felt" while undergoing treatment with this particular drug or protocol.
But regrettably, he writes, this information is generally missing from drug labels in the United States and from clinical trial data.
Cancer drug labels stand out in sharp contrast to those of therapeutics for other conditions, Dr. Basch points out. About 25% of drugs list their effects on patients' symptoms or functioning, and that "disparity is surprising, considering how common symptoms and functional impairment are in patients with cancer and how toxic oncology agents can be."
As an example, in 2011 the FDA approved 15 hematology/oncology drugs, but in only one case was symptom information included in the portion of the label that manufacturers can legally use for marketing purposes. This was for ruxolitinib (Jakafi, Incyte), which received approval for management of myelofibrosis. In fact, Dr. Basch notes, this was the first oncologic drug for which symptom information was included in a US drug label in over a decade. In preapproval trials, symptom or functional-status evaluations of patients that meet the FDA's standards are rare.
"Some experts have argued that the FDA has raised the methodologic bar too high, whereas others accuse the pharmaceutical industry of paying too little attention to patients' experiences," he writes. "The bottom line is that both regulators and industry continue to prioritize survival-based end points rather than patient-experience end points in cancer-drug development."
The notion of making drug development more patient centered has grown in importance as cancer patients are living longer with the disease and must increasingly chose among therapies that have varying efficacy-toxicity balances. He notes that as new drugs continue to yield only tiny median survival benefits — all too often measured in weeks — it is understandable that cancer patients would like to know the experiences of their peers during and after treatment.
In addition, payers are increasingly looking for information about comparative experiences with different products, as those with more severe symptoms or functional status utilize more supportive services.
Key Steps for Drug Development
In his commentary, Dr. Basch outlined what he believes are key steps to improving drug development and allowing it to be more patient centered.
Step 1 would be for the drug developer to identify patient-centered outcomes (symptom, functional, and other outcomes affected by a disease or product and important to patients) through direct patient feedback. This ideally would be done prior to a pivotal trial, and patient-centered outcomes would be prioritized at the earliest stages of drug development.
For step 2, plans for measuring and analyzing patient-centered outcomes would be discussed at structured meetings between the drug development team and the regulatory agency. This would be done throughout the development life cycle of the agent, beginning in early phase I studies. Meetings between developers and regulators would be formalized, and discussions would include prioritizing end points that are meaningful to patients.
The third step would require the drug developer to formulate or select measures to evaluate outcomes using established qualitative and quantitative methods, which would be done prior to pivotal trials. This would be completed prior to designing the trial to ensure the appropriate selection of key and exploratory patient-centered end points, an adequate understanding of how measures will perform, anticipated effect sizes, and adherence to regulatory guidance.
In step 4, the drug developer would use patient-centered measures in pivotal trials, with protocol-specified plans for statistical analysis and minimizing and handling missing data.
They would dedicate statistical power for the analysis of selected key patient-reported outcome end points with support from exploratory end points.
In step 5, the drug developer and regulatory agency would include a representative sample of the target population throughout the drug-development life cycle. Formalized approaches to obtain patient input on study inclusion criteria should be used for outcomes, measures, end-point design, comparators, strategies for accruing and retaining participants, and plans for dissemination and implementation.
Finally, in the 6th and final step, patient-reported outcomes would be included in drug labels to help both patients and their providers with treatment decision-making. This would create a pathway for information about fatigue and health-related quality-of-life domains, facilitate qualification of existing patient-reported outcome measures, and suggest measures of cross-cutting patient reported outcomes that perform well in multiple subpopulations.
Dr. Basch has disclosed no relevant financial relationships.
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