Are adverse events reported accurately in anti-cancer clinical trials?
- Adverse events (AEs) were found to be suboptimally reported in a number of publications
- AE description should be improved in both trials and post-marketing safety analyses
- Inadequate reporting could have a significant impact on patients’ quality of life
A critical look at trials that tested immunotherapy and targeted therapies found that AEs are not reported to an acceptable standard, explained Dr Paolo Bossi, Medical Oncologist, Istituto Nazionale Tumori, Milan, Italy. His research, presented at the Congress of the European Society for Medical Oncology, October 2016, underlined that current reporting is in need of improvement.
“It is essential [to] engage patients and the physician in shared decision making,” Dr Bossi said. Dr Bossi explained that in his practice, he openly describes possible treatment plans with his patients, weighing out benefits and risks. He believes it is imperative to explain AEs that the patient may experience during treatment clearly and transparently.
“We should be critical in reading new papers; we should ask that new trials pay a greater attention to patient-reported outcomes and to several ways of reporting other aspects, like duration of AEs.”
Dr Paolo Bossi, Medical Oncologist, Istituto Nazionale Tumori, Milan, Italy
“There are several aspects which are important in the reporting of AEs, I think that the most important is the duration.” Dr Bossi explained that primarily focusing on the grades of AEs seen in clinical trials can be misleading. A high grade AE, for example neutropenia, may only last for a short amount of time. However, a lesser grade event, lasting an extended amount of time, can have a significant impact on a patient’s quality of life; “I think that the topic of duration will impact so much in the future.”
Dr Bossi and his team reviewed 81 trials examining the use of immunotherapies and targeted therapies that have been approved for solid malignancies from 2000 to 2015. The majority of trials studied melanoma, colorectal, lung and breast cancers. Most (95.1%) of the 45,084 patients studied had metastatic cancer.
The trials were analysed using a 24-point score based on Consolidated Standards of Reporting Trials (CONSORT). The score allowed qualitative data, such as “Was the discussion consistent between interpretation and reporting of AEs?”, “Did the discussion provide a balanced discussion of benefits and harms?” and “Did the article describe if AEs were attributed to trial drugs?” to be quantified.
The analysis, overall, found that reporting of AEs was suboptimal. Areas lacking in adequate reporting included: recurrent and late toxicities (>90% publications), duration of AEs (94%), time of AE occurrence (86%), report of all events (not just those above a fixed threshold; 75%).
Statistical methods used to report AEs were found to be inadequate in 63% of the publications studied, as were descriptions of toxicities leading to withdrawal (57%) and indication of follow-up interval assessments (51%). Notably, only 38% of publications reviewed reported the number of patients requiring a dose adjustment due to AEs.
Although Dr Bossi appreciates that fast tracking practice-changing drugs is important for tackling real unmet needs, he believes the downside of this can be the underreporting of AEs. Dr Bossi thinks this is somewhat concerning as it could have a significant impact on a patient’s quality of life.
When asked what the learnings from the analysis were, Dr Bossi stated “we should be critical in reading new papers; we should ask that new trials pay a greater attention to patient-reported outcomes and to several ways of reporting other aspects, like duration of AEs.”
Based on Bossi P, Botta L et al. Systematic review of adverse events reporting in clinical trials leading to approval of targeted therapy and immunotherapy (320P). Presented on Monday 10 October 2016.
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