Lack of pre-planned financial outcomes evaluation in phase 3 cancer trials.
Authors: Noticewala Sonal S. , Jaoude Joseph Abi , Kouzy Ramez , Patel Roshal , Chino Fumiko , Smith Grace L. , Fuller Clifton Dave , Thomas Charles R. , Koong Albert C. , Das Prajnan , Taniguchi Cullen M. , Ludmir Ethan B. 
Published: June 2021

e18826

Background: New cancer treatments have the potential to cause economic stress at the personal and societal level. Little is known on the evaluation of financial outcomes in clinical trials. We hypothesized that randomized controlled trials (RCTs) are unlikely to have pre-planned analyses to look at economic outcomes that address financial toxicity to patients and cost-effectiveness to society. Methods: Interventional therapeutic-intent phase 3 cancer-specific RCTs were identified through ClinicalTrials.gov. Pre-planned economic outcomes addressing financial toxicity or cost-effectiveness were identified. Results: We identified 1,069 interventional phase 3 oncology RCTs. Overall, 101 (9.4%) had pre-planned to evaluate quality of life using the European Organization for Research and Treatment of Cancer Quality of Life (QOL) Questionnaire (EORTC QLQ-C30) instrument, of which a single question (Q28) relates to financial toxicity. However, only ten (0.94%) trials included pre-planned financial/economic endpoints; all were secondary endpoints. Among those planning to evaluate economic outcomes, 6/10 planned to collect data and report on financial distress using Q28 on EORTC QLQ-C30 and 3/10 pre-planned performing cost-effectiveness analyses. One study planned to perform an economic evaluation, including health utilities, as measured by the EuroQol-Five Dimension (EQ-5D) Questionnaire. All ten trials were industry–sponsored, and two were co-sponsored by a National Cancer Institute (NCI) cooperative group. The majority (8/10) were superiority-designed trials, and 6/10 included progression-free survival as the primary endpoint. The majority (6/10) assessed targeted therapy as the primary intervention. Multinational enrollment was predominant (8/10). Of the 10 trials, nine had a published manuscript. One was closed because of accrual issues. Among the six trials that had pre-specified reporting on financial distress, two published on financial toxicity. Of the two trials that had a priori planned to do a cost-effective analysis, one was published. However, overall 3/9 had published a cost-effective analysis. Conclusions: Less than one percent of oncology RCTs have pre-specified plans to evaluate economic outcomes associated with personal financial distress or cost-effectiveness. For the trials that had pre-planned reporting on financial toxicity, the instrument used to evaluate financial toxicity is a single question which has not been validated as a standalone assessment. Cost-effectiveness analyses were more likely to be published than on financial toxicity and were often completed as a post-hoc analysis. Given that many newly investigated therapies increase the financial burden on patients and add cost to the healthcare system more broadly, pre-planned evaluation of economic outcomes in RCTs is imperative in order to create a value-based framework in assessing new therapies.