Clinical drug trials or studies are usually conducted to assess how well the drug works but also whether it causes any harm (side effects or adverse effects). Adverse effects can be detected by the trial doctor examining participants or taking some blood samples or doing other kinds of tests. The trial staff can also ask participants about how they are feeling after taking the trial drug. However, the way participants are asked about their health can vary from trial to trial, or even within a trial. In some trials, participants may be asked a simple open question such as ‘how have you been feeling?’, while in other trials, participants may be asked about whether they have had any of a long list of possible symptoms (such as ‘have you had a headache, stomach ache, or sore muscles?’). There has been concern that these different kinds of questions and how they are phrased will impact on what participants report about their health during a trial. This might then affect the trial‘s results and what we know about the side effects of drugs.

We did this review to look at studies that compared different types of participant questioning methods in order to investigate these issues. We found 33 studies comparing mainly open questions with checklist-type questions, but also some ratings scales and participant interviews. While the studies were all very different in terms of the types of disease, drugs, and patients studied, we found in general that, as would be expected, when a more specific type of question was asked (like a checklist), participants reported more symptoms. What is interesting is that, in those studies that looked more closely at the types of symptoms reported, it seems that an open question picks up the more severe or bothersome symptoms compared to a checklist-type question. However, some studies found that even quite severe or bothersome symptoms were not reported when a participant is asked an open question and these severe symptoms will only be reported with the more specific question. This makes it difficult to say whether one method is better than any other and the different questioning methods may, in fact, be complementary and therefore should be used together. It is also difficult to say what a specific question should include, as it might take too long for a participant to have to answer a very long list. While more research is needed to resolve the remaining uncertainties, it is very important for trials to be clear about which kind of questioning was used when they publish their results. This will help readers understand the trial‘s findings about the side effects and make it easier to make accurate comparisons between trials.