In a head-to-head clinical trial, researchers are not comparing an intervention against a placebo or sham control but instead are comparing two different interventions that have each previously been shown effective. The goal is to identify which intervention is safer and/or more effective at treating the same condition. Head-to-head trials might also be performed to compare cost-effectiveness of different interventions with similar efficacy and safety profiles, or to measure adherence of participants or acceptance or feasibility by participants, especially if one or both interventions is not a drug but instead a type of psychotherapy, surgical procedure or physical therapy.
Deeper dive
Head-to-head trials can compare a new drug not yet approved by the FDA to a drug already on the market for the same condition, or they can compare two drugs already on the market. Sometimes they may even compare two drugs that have not yet been approved, though this typically only occurs if both drugs come from the same pharmaceutical manufacturer. Head-to-head trials might be performed after a drug is approved or at the same time as a phase 3 trial to provide data on benefit compared to first-line therapies or standard of care. Head-to-head trials have sometimes been proposed as an outright alternative to placebo-controlled trials, but those would be unlikely to pass muster with the FDA; they’re typically best as complementary trials.
In reporting on a head-to-head trial, you’ll want to pay special attention to the design and procedures. Is it blinded? Is it possible to blind it? What are the primary endpoints? Are the investigators likely trying to show their drug is better than another, or is it an independent group comparing two drugs for nothing other than the purpose of improving clinical care? Is the primary goal to assess safety, efficacy, cost-effectiveness, adherence, or patient satisfaction? It’s important to get outside opinions when writing about any clinical trial, but it’s particularly helpful to ask outside sources about the design of a head-to-head trial and whether they see any concerns, red flags, opportunities for bias or other issues that need to be considered.