Economic Evaluation of Cost and Time Required for a Platform Trial vs Conventional Trials

Abstract

Importance: Platform trial design allows the introduction of new interventions after the trial is initiated and offers efficiencies to clinical research. However, limited guidance exists on the economic resources required to establish and maintain platform trials.

Objective: To compare cost (US dollars) and time requirements of conducting a platform trial vs a series of conventional (nonplatform) trials using a real-life example.

Design, setting, and participants: For this economic evaluation, an online survey was administered to a group of international experts (146 participants) with publication records of platform trials to elicit their opinions on cost and time to set up and conduct platform, multigroup, and 2-group trials. Using the reported entry dates of 10 interventions into Systemic Therapy in Advancing Metastatic Prostate Cancer: Evaluation of Drug Efficacy, the longest ongoing platform trial, 3 scenarios were designed involving a single platform trial (scenario 1), 1 multigroup followed by 5 2-group trials (scenario 2), and a series of 10 2-group trials (scenario 3). All scenarios started with 5 interventions, then 5 more interventions were either added to the platform or evaluated independently. Simulations with the survey results as inputs were used to compare the platform vs conventional trial designs. Data were analyzed from July to September 2021.

Exposure: Platform trial design.

Main outcomes and measures: Total trial setup and conduct cost and cumulative duration.

Results: Although setup time and cost requirements of a single trial were highest for the platform trial, cumulative requirements of setting up a series of multiple trials in scenarios 2 and 3 were larger. Compared with the platform trial, there was a median (IQR) increase of 216.7% (202.2%-242.5%) in cumulative setup costs for scenario 2 and 391.1% (365.3%-437.9%) for scenario 3. In terms of total cost, there was a median (IQR) increase of 17.4% (12.1%-22.5%) for scenario 2 and 57.5% (43.1%-69.9%) for scenario 3. There was a median (IQR) increase in cumulative trial duration of 171.1% (158.3%-184.3%) for scenario 2 and 311.9% (282.0%-349.1%) for scenario 3. Cost and time reductions in the platform trial were observed in both the initial and subsequently evaluated interventions.

Conclusions and relevance: Although setting up platform trials can take longer and be costly, the findings of this study suggest that having a single infrastructure can improve efficiencies with respect to costs and efforts.

Figure 1.. Competing Scenarios: A Platform Trial vs Multiple Conventional Clinical Trials

According to Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy (STAMPEDE), 3 competing scenarios that would all evaluate 10 interventions are illustrated here. The first scenario involves a single platform trial with a single common control group that would be used for evaluation of 10 intervention groups. The second scenario involves a 6-group trial followed by 5 independent 2-group trials (10 intervention plus 6 control groups), and the third scenario involves 10 independent 2-group trials (10 intervention plus 10 control groups). The same start time for all 3 competing scenarios were used in our simulations.

Figure 2.. Scatterplots of Setup Times for a Single Platform Trial vs a Multigroup Trial, 2-Group Trial, a Multigroup Plus 2-Group Trials, and 2-Group Trials

In panels A and B, scatterplots of setup times for a single platform trial (y-axes) and a single multigroup trial and a single 2-group trial (x-axes) are shown, respectively. Comparison of total setup times between the scenario 1 (a single platform trial) vs scenario 2 that involves 1 multigroup trial plus 5 two-group trials is shown in panel C, and panel D shows the comparison of total setup times between scenario 1 vs scenario 3 (10 two-group trials). Dashed lines denote the lines of equality.

Figure 3.. Total Costs of Evaluation of all 10 Interventions: A Platform Trial vs Conventional Multiple Trials

For interventions with reported treatment effects (hazard ratio [HR] and 95% CIs) on failure-free survival (FFS) and overall survival (OS) from Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy (STAMPEDE), we used the point estimate as the base case, the lower CI as the best case, and the upper CI as the pessimistic case for our simulations. For the 3 intervention groups without reported results, we assumed the base case FFS and OS to have an HR of 0.75, which was the target treatment effect by the STAMPEDE investigators.^, The best case for these intervention groups assumed a treatment effect of 0.5625, twice the treatment effect of the target effect, for both FFS and OS, and the pessimistic case assumed that these interventions would have no treatment effects on either outcome (HR = 1.00).

Figure 4.. Scatterplots of the Total Trial Cost Required for Clinical Evaluation of the Subsequent 5 Interventions: A Platform Trial vs Conventional Multiple 2-Group Trials

For interventions with reported treatment effects (hazard ratio [HR] and 95% CIs) on failure-free survival (FFS) and overall survival (OS), we used the point estimate as the base case, the lower CI as the best case, and the upper CI as the pessimistic case for our simulations. For the 3 intervention groups without reported results, we assumed the base case FFS and OS to have an HR of 0.75, which was the target treatment effect by the Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy (STAMPEDE) investigators. The best case for these intervention groups assumed a treatment effect of 0.5625, twice the treatment effect of the target effect, for both FFS and OS, and the pessimistic case assumed that these interventions would have no treatment effects on either outcome (HR = 1.00). Dashed lines denote lines of equality.