Cancer trial toxicity reporting inconsistent, often uses ‘subjective minimizing language’
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Abstracts of randomized phase 3 clinical trials in gastrointestinal oncology frequently use subjective minimizing language to characterize serious toxicities, according to results of a systematic review presented at ASCO Annual Meeting.
“The argument that we made in this paper is that we should consider no longer using these terms and instead report objective metrics,” Bishal Gyawali, MD, PhD, associate professor in medical oncology and public health sciences and scientist in the division of cancer care and epidemiology at Queen’s University in Canada, told Healio.
“For example, instead of saying a treatment is ‘well-tolerated,’ we should say that 30% of patients had serious adverse events,” Gyawali added. “If we want to use these terms for the sake of great abstracts, then we should start collecting that data.”
Investigators could do that by asking patients if they consider adverse events to be acceptable, Gyawali said.
“Then, instead of subjectively reporting that the adverse events were acceptable, we can say, ‘Forty percent of patients considered the adverse events to be acceptable,’” Gyawali said. “[That would] make it more objective and not downplay the risk of harm.”
Gyawali and colleagues — including Nicole M. Kuderer, MD, MS, FASCO, faculty member in the department of medicine at University of Washington — reviewed abstracts of 63 randomized phase 3 clinical trials in colorectal cancer and pancreatic cancer presented at ASCO Annual Meeting between 2012 and 2022.
They determined 15 (24%) of those abstracts used "any subjective minimizing language" and that 60 (95%) of them used subjective or objective toxicity minimization. Information about serious adverse events also is frequently absent or incomplete, investigators concluded.
Gyawali discussed the study’s findings and their potential implications.
Healio: What motivated you to conduct this study?
Gyawali: I published a paper in 2018 in The BMJ that looked into how clinical trials use subjective minimization terms to downplay risks for toxicity. I highlighted certain terms — such as “tolerable,” “manageable” or “acceptable” — that often were used subjectively to describe harms in cancer clinical trials. Some of the findings were very surprising. In one trial, toxicities were described as “manageable,” but several patients died of adverse events. If a patient died, by definition, it is not manageable.
Other abstracts described a drug as “well-tolerated,” but who did [investigators] ask? A high percentage of patients in one trial had serious diarrhea — that is, more than six episodes of diarrhea a day for several weeks. I don’t think anybody would call that “well-tolerated.”
After that paper was published, meeting attendees would photograph slides that described adverse events in clinical trials as “tolerable,” “manageable” or “well-accepted” and post them social media. They would then link to my article, stating that we need to change the language.
At the end of an ASCO meeting a few years ago, a discussion focused on using proper language. That was a step in the right direction, but it mostly focused on using a clinician’s appropriate title. Language that is respectful and inclusive was very much promoted, which is absolutely the right thing. However, we also wanted to include this language about discussing potential harms accurately without downplaying them.
Dr. Kuderer and I — along with our team — looked at abstracts presented at ASCO that evaluated GI cancers to see how often these minimization terms were used.
Healio: What did you find?
Gyawali: We found that 17% of abstracts did not include any information about adverse events. Sixty percent (n = 38) provided quantitative data on adverse events, but reporting on serious adverse events often was absent. Only seven abstracts (11%) noted the occurrence or absence of fatal adverse events.
Fifteen abstracts (24%) included subjective minimizing language. None of the abstracts that used subjective minimizing language offered information about rates of fatal adverse events. These abstracts also failed to report on the patient perspective through patient-reported outcomes or quality-of-life measures.
These findings were not very surprising. We already knew this language existed in many abstracts. Now we have data to show what percentage of abstracts use this language and the type of language used.
We have held ourselves to a relatively high standard in terms of reporting efficacy of drugs in trials but, as a community, we have not held ourselves to similarly high standards in reporting adverse events. This study is one step in the right direction. I hope this will convey the message that using these subjective, generalized terms is unacceptable.
Healio: Why do you think these studies use subjective minimizing language?
Gyawali: Some might argue it is for the sake of brevity. Instead of discussing all adverse events, it is more concise to say these events were “tolerable” or “acceptable.” However, you don’t want to achieve brevity by being misleading. You want to be correct, as well. We collect patient-reported outcomes all the time. If we want brevity, we can the percentage of patients who considered adverse events to be manageable. That does not change the abstract length.
Healio: What are the potential implications of these findings?
Gyawali: We are asking for greater transparency and the avoidance of subjective minimizing language. We cannot understand adverse events of a treatment based on this language alone. We also would like to see a guideline that states this sort of language is not acceptable. We need to provide updated data using objective language or patient-reported outcomes. Reporting quality of life may be another way to describe harms and adverse events of a treatment. Quality-of-life information is an indicator of harms, and it also is an indicator of clinical benefit. Instead of saying “toxicities were manageable,” a paper could note that quality of life was improved based on objective evaluation using validated tools.
References:
- Gyawali B, et al. BMJ. 2018;doi:10.1136/bmj.k4383.
- Yu J, et al. Abstract 1567. Presented at: ASCO Annual Meeting, June 2-6, 2023. Chicago.
For more information:
Bishal Gyawali, MD, PhD, can be reached at Queen’s Cancer Research Institute, 10 Stuart St., Kingston, ON K7L, 3N6, Canada. Email: bg.bishalgyawali@gmail.com.
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Yu J, et al. Abstract 1567. Presented at: ASCO Annual Meeting, June 2-6, 2023. Chicago.
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