David Ruben Teindl Laursen

What is the title of your thesis?

Active placebo as a control intervention in pharmacological randomised trials.

At which department and/or research unit did you complete your PhD?

Department of Clinical Research, Cochrane Denmark & Centre for Evidence-Based Medicine Odense (CEBMO).

Who was your principal supervisor?

Asbjørn Hróbjartsson, Professor at Cochrane Denmark & Centre for Evidence-Based Medicine Odense (CEBMO).

What question did you aim to answer with your thesis?

My dissertation examined the significance, development and terminology of active placebo control interventions in drug trials.

What did you find?

Regarding the significance of active placebos, my co-authors and I found, on average, no difference between the treatment effects of drugs when active placebos (which attempt to mimic the noticeable effects of drugs) were used as controls and the treatment effects when standard placebos (which do not mimic noticeable effects) were used as controls.

This may be because, on average, there is in fact no difference, regardless of the type of placebo control used. Alternatively, it may be due, among other things, to statistical uncertainty resulting from too few studies being available for the analyses, or to other systematic differences between the studies that obscure the average result.

Regarding the development of active placebos, this followed five phases, from specifying the requirements for a satisfactory active placebo through to evaluating a final candidate in a trial. In terms of terminology, the term active placebo was used in several senses beyond the one we used.

We also identified several different subtypes of active placebos within our meaning of the term.

How did you do it?

My co-authors and I conducted three studies that formed part of my dissertation. The first study was a systematic review that investigated the significance of active placebos by collecting and analysing randomised trials that directly compared treatment effects using an active placebo versus a standard placebo as the control (i.e. within the same trial).

The second study also investigated the significance of active placebos, but did so by collecting and analysing treatment effects from trials using active placebos and from similar trials using standard placebos (i.e. across similar trials). The two studies therefore complemented each other.

The third study firstly mapped studies describing the development of active placebos and secondly analysed the terminology used for active placebos in publications.

How can your research be applied (in the clinic, society, etc.)?

Contrary to what one might expect, it is not clear from a scientific perspective whether an active placebo is better than a standard placebo. Until this has been clarified further in future studies, researchers planning drug trials should carefully consider which type of placebo control makes sense in their particular case.

If they are considering an active placebo, they can draw on the five phases of development and the different subtypes of active placebo when planning their trial.