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Brief Report
February 4, 2021

Updating Reports of Phase 3 Clinical Trials for Cancer

Author Affiliations
  • 1Division of Medical Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
  • 2Division of Biostatistics, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
  • 3now with Department of Medical Oncology, Institute of Oncology, Ljubljana, Slovenia
JAMA Oncol. 2021;7(4):593-596. doi:10.1001/jamaoncol.2020.6968
Key Points

Question  How many phase 3 randomized clinical trials for cancer are updated after the initial report, and which factors are associated with the updates?

Findings  In this study, 41 of 207 phase 3 trials (20%) had initial reports that were updated; the factors associated with updating were positive trial results, larger trial size, evaluation of adjuvant therapy, and evaluation of hormonal or targeted agents. The hazard ratio for the primary end point increased in the 31 updated trials for which values were available, indicating decreased effect size.

Meaning  Updating of phase 3 trials is uncommon and should be mandated to provide mature results.

Abstract

Importance  Phase 3 randomized clinical trials (RCTs) are usually reported after a predetermined number of events (death or disease progression) have occurred, when survival curves remain poorly defined. Updated reports are important in providing mature data.

Objectives  To evaluate the proportion of phase 3 RCTs for cancer that are updated and the factors that are associated with updating them and, for updated trials, to compare initial and updated results.

Design, Setting, and Participants  This study identified reports of 2-group RCTs with a sample size of at least 100, published in 6 major journals between 1990 and 2010, that evaluated drug treatments for breast, lung, or prostate cancer. PubMed and abstracts of large cancer conferences were searched to identify updated (or earlier) reports of the same trials published up to 2019. Logistic regression was used to identify factors associated with the provision of updated reports. The hazard ratios defining the relative treatment effects for the primary and secondary end points between the initial and updated reports were compared.

Main Outcomes and Measures  Proportion of RCTs whose results are updated, factors associated with updating, and change in hazard ratio for the primary end point between initial and updated reports.

Results  A total of 207 RCTs met the inclusion criteria, and 41 (20%) were found to have updated reports. The factors significantly associated with an update included positive trial results (odds ratio [OR], 8.7 [95% CI, 3.3-23.3]), larger trial size (OR, 1.0006 [95% CI, 1.0000-1.0012]), evaluation of hormonal agents (OR, 5.8 [95% CI, 1.6-21.8]) or targeted agents (OR, 4.3 [95% CI, 1.3-14.6]) compared with chemotherapy, and evaluation of adjuvant therapy rather than therapy for advanced disease (OR, 8.0 [95% CI, 2.9-21.9]). For 31 trials for which initial and updated hazard ratios for the primary end point were available, the median hazard ratio increased from 0.66 (95% CI, 0.22-1.20) to 0.74 (95% CI, 0.32-1.19) (P < .001), indicating a decreased level of effectiveness.

Conclusions and Relevance  Only 20% of reports of phase 3 clinical trials for breast, lung, and prostate cancer were updated. Original reports of such trials are based on relatively few events, and their results are immature; more mature data indicate a decreased level of effect in updated trials. Updated reporting to provide mature, long-term results of clinical trials should be mandated.

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