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Changes in cancer trial designs after enrollment initiation are common, often unreported
Changes in the design of cancer drug trials after patient enrollment began appeared common and were left frequently unreported, according to a research letter published in JAMA Oncology.
Such changes “can affect the scientific basis of evidence-based medicine and should be reported and justified,” Daniel Shepshelovich, MD, medical oncology fellow at Princess Margaret Cancer Centre and University of Toronto, and colleagues wrote. “Data on the prevalence of these changes in oncology drug development are scarce.”
Shepshelovich and colleagues searched the FDA website in April 2017 for trials supporting approval of new drugs to treat solid tumors between Jan. 1, 2010, and Dec. 31, 2016. They identified changes in trial design by comparing ClinicalTrials.gov entries at the beginning of trials with entries for the same trials as of April 1, 2018. They then reviewed the publications of the registered studies and evaluated reporting of the changes.
Of 101 trials reviewed, 56 (55.4%) had changes in planned sample size, 39 of which (69.6%) were reported in matching publication. Thirty-four (33.7%) had modifications to inclusion criteria — 19 of which (55.9%) were reported in the publication — and 27 (26.7%) had changes in primary outcome, 10 of which (37%) were reported.
Breakthrough therapy designation — initiated in 2012 — appeared associated with more changes in inclusion criteria (OR = 2.73; 95% CI, 1.01-7.39) and primary outcome definitions (OR = 3.95; 95% CI, 1.11-14.13).
Accelerated approval was associated with a greater number of changes to inclusion criteria (OR = 2.84; 95% CI, 1.12-7.21) and sample size (OR = 2.71; 95% CI, 1-7.34).
Single-arm trials appeared more likely to have changes in sample size (OR = 4; 95% CI, 1.33-12.50).
Researchers observed no association between changes in study design and tumor size, drug type or other regulatory pathways.
should demand more transparent justification for changes to the trial design after commencement of patient accrual.” – by Jennifer Byrne
Disclosure s : Shepshelovich reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.