RESUMO
BACKGROUND: Conducting high-quality randomised clinical trials (RCTs) is challenging and resource intensive. Funders and academic investigators depend on limited financial resources and, therefore, need empirical data for optimal budget planning. However, current literature lacks detailed empirical data on resource use and costs of investigator-sponsored RCTs. The aim of this study is to systematically collect cost data from investigator-sponsored RCTs from Switzerland, Germany, and the United Kingdom (UK). METHODS: Principal investigators were asked to share their RCT cost and resource use data and enter it into an online case report form. We assessed cost patterns, cost drivers, and specific cost items, examined costs by study phase (planning-, conduct-, and finalisation phase), compared planned with actual RCT costs, and explored differences in cost patterns across countries, medical fields, and intervention types. RESULTS: We included 93 RCTs which were initiated in Switzerland (n=53; including 8 conducted in low- and lower middle-income countries), Germany (n=22), and the UK (n=18). The median total trial cost in our RCT sample was $645,824 [Interquartile range (IQR), $269,846 to $1,577,924]. The median proportion of the total costs spent for planning phase was 27.5% [IQR, 20.6 to 39.7%], for conduct phase 57.3% [IQR, 44.4%-66.3%], and for finalisation phase 12.7% [IQR, 8.5% to 19.3%] with little variation across countries. The items that contributed most to the total costs were protocol writing (7.2%; IQR 3.8% to 10.6%), data management (5.0%; IQR 2.2% to 8.1%) and follow up (4.5%; IQR 2.3% to 8.4%). Of the 66 RCTs with an available original budget, 46 (69.7%) exceeded the budget by over 50%. Use of routinely collected data to assess primary outcomes was independently associated with lower per patient- and lower total trial costs. CONCLUSIONS: Over a quarter of total trial costs were incurred in the planning phase, which is typically not fully funded. Two thirds of RCTs exceeded their budget by more than 50%. Investigators and funders should consider empirical cost data to improve budgeting and funding practices.
RESUMO
Importance: Platform trials have become increasingly common, and evidence is needed to determine how this trial design is actually applied in current research practice. Objective: To determine the characteristics, progression, and output of randomized platform trials. Evidence Review: In this systematic review of randomized platform trials, Medline, Embase, Scopus, trial registries, gray literature, and preprint servers were searched, and citation tracking was performed in July 2022. Investigators were contacted in February 2023 to confirm data accuracy and to provide updated information on the status of platform trial arms. Randomized platform trials were eligible if they explicitly planned to add or drop arms. Data were extracted in duplicate from protocols, publications, websites, and registry entries. For each platform trial, design features such as the use of a common control arm, use of nonconcurrent control data, statistical framework, adjustment for multiplicity, and use of additional adaptive design features were collected. Progression and output of each platform trial were determined by the recruitment status of individual arms, the number of arms added or dropped, and the availability of results for each intervention arm. Findings: The search identified 127 randomized platform trials with a total of 823 arms; most trials were conducted in the field of oncology (57 [44.9%]) and COVID-19 (45 [35.4%]). After a more than twofold increase in the initiation of new platform trials at the beginning of the COVID-19 pandemic, the number of platform trials has since declined. Platform trial features were often not reported (not reported: nonconcurrent control, 61 of 127 [48.0%]; multiplicity adjustment for arms, 98 of 127 [77.2%]; statistical framework, 37 of 127 [29.1%]). Adaptive design features were only used by half the studies (63 of 127 [49.6%]). Results were available for 65.2% of closed arms (230 of 353). Premature closure of platform trial arms due to recruitment problems was infrequent (5 of 353 [1.4%]). Conclusions and Relevance: This systematic review found that platform trials were initiated most frequently during the COVID-19 pandemic and declined thereafter. The reporting of platform features and the availability of results were insufficient. Premature arm closure for poor recruitment was rare.