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Underreporting of adverse event duration impairs physician, patient decision-making
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Information about the duration of adverse events during clinical trials often is not reported, according to the author of an editorial published in The Oncologist.
Understanding risk is critical for patient decision-making and failure to include more comprehensive information about adverse event duration can prevent both physicians and patients from making accurate risk assessments, Oliver Sartor, MD, told HemOnc Today.
Although the omission of this information may not be intentional, the manner in which event reporting is presented in clinical trials leaves no room for these more nuanced details, said Sartor, professor of medicine, medical director of Tulane Cancer Center, and C.E. and Bernadine Laborde professor of cancer research at Tulane University.
HemOnc Today spoke with Sartor about why information about adverse event duration is not included in clinical trial reports, as well as why he believes more comprehensive analysis and clearer presentation of this information is necessary.
Question: Are data about adverse event duration left out in every clinical trial report?
Answer: Virtually all of the time. It is rare that it would be included. In a typical scenario, the data would be left out even of The New England Journal of Medicine, which, in my opinion, is the premier journal. Adverse event data is not displayed in a manner that the reader could elucidate, and it bugs me. A lot of oral drugs have side effects that could persist for weeks or months, and you just can’t see that information. The initial tables for chemotherapy drugs given episodically, for example, might show grade 1 vomiting as an event. But this doesn’t tell the whole story. If you vomit once and it goes away the next day, it’s not so terrible. If you vomit every day for a month, that’s dreadful. So, we need to be looking at continuous versus episodic drugs, and that information needs to be displayed in the event tables.
Q: Why is this information valuable?
A: This is part of the risk-benefit assessment for any treatment. It is part of the risk patients incur. When you get this bewildering array of tables, you’re left without a true assessment of risk. You are missing a true component of it. If you lack this important component, your decision-making is impaired. People have to be informed about risk in order to best manage their therapeutic choices. This information will lead to more accurate assessments.
Q: Is this an intentional omission?
A: Like many things in medicine, it’s a historic evolution. We are somewhat mired in the past in terms of adverse event reporting. In the 1980s, Robert Wittes, MD, at NCI led an effort to put together the first common toxicity criteria for adverse events (CTCAEs). He standardized criteria. What he did was really important because it brought together this toxicity reporting in such a way that you could have a common denominator. He did that in the chemotherapy era, and there were very few oral chemotherapeutic agents. So, his criteria weren’t applicable to other such therapies which, admittedly, were rare at that time. We have stuck with this CTCAE formula since that time. That’s what we accept, and what we report in major journals. The field has evolved to different types of therapy. These criteria are no longer adequate for drugs given continuously as opposed to those given episodically.
Q: Is there momentum to make these changes?
A: I think there is. I’m on a panel with some FDA members, and they agree. They are in the midst of attempting to revamp the way toxicity is reported. I can’t guarantee that this issue will be addressed. It is worth noting that the real audience here is regulators, because they determine how things will be reported. I think this could have major impact. We are already seeing impacts. There are other groups looking into similar issues. I got a very lively email from Ayal K. Abdulahad, MB, ChB, PhD, MSc, MRCPath, FRCPath, who has been looking at the concept of “burdens of therapy.” He had similar feelings and has given considerable thought to this problem.
Q: What should happen next?
A: The first step would be regulatory change by FDA. That can be done through its due course, but highlighting the concern is step one. The defect is in clinical trial reporting. That’s done in the context of a structured environment. Clinical trialists and regulators will have to come to an agreement. I haven’t heard anybody disagree with me. But it’s challenging, because most of us are doing more work than is humanly feasible. Often, nobody gets around to actually reporting these adverse event data. A regulatory change by the FDA could improve that.
Q: How much work would it be for researchers to tabulate and report these data?
A: None. I’m involved in ongoing clinical trials, and we collect and record those data already. It would not be an impediment to clinical trialists, it would just be a matter of reporting the information. – by Rob Volansky
Reference:
Sartor O. Oncologist. 2018;doi:10.1634/theoncologist.2017-0437.
Abdulahad AK, et al. Contemp Clin Trials Commun. 2016;doi:10.1016/j.conctc.2016.09.003.
For more information:
Oliver Sartor, MD, can be reached at Tulane Cancer Center, Tulane University School of Medicine, 1430 Tulane Ave., Box SL-42, New Orleans, LA 70112; email: osartor@tulane.com.
Disclosure: Sartor reports no relevant financial disclosures.