It makes no sense to perform clinical research that has no relevance to patient care, so why do we do it, and how can we stop? John Ioannidis ponders the problem and offers some suggestions.
Practicing doctors and other health care professionals will be familiar with how little of what they find in medical journals is useful.
The term ‘clinical research’ is meant to cover all types of investigation that address questions on the treatment, prevention, diagnosis/screening, or prognosis of disease or enhancement and maintenance of health.
Experimental intervention studies (clinical trials) are the major design intended to answer such questions, but observational studies may also offer relevant evidence.
‘Useful clinical research’ means that it can lead to a favorable change in decision making (when changes in benefits, harms, cost, and any other impact are considered) either by itself or when integrated with other studies and evidence in systematic reviews, meta-analyses, decision analyses, and guidelines.
There are many millions of papers of clinical research – approximately 1 million papers from clinical trials have been published to date, along with tens of thousands of systematic reviews – but most of them are not useful.
In order to be useful, clinical research should be true, but this is not sufficient.
Research inferences should be applicable to real-life circumstances. When the context of clinical research studies deviates from typical real-life circumstances, the question critical readers should ask is, to what extent do these differences invalidate the main conclusions of the study?
A common misconception is that a trial population should be fully representative of the general population of all patients (for treatment) or the entire community (for prevention) to be generalizable.
Randomized trials depend on consent; thus, no trial is a perfect random sample of the general population. However, treatment effects may be similar in nonparticipants, and capturing real-life circumstances is possible, regardless of the representativeness of the study sample, by utilizing pragmatic study designs.
Pragmatism has long been advocated in clinical research, but it is rare. Only nine industry-funded pragmatic comparative drug effectiveness trials were published between 1996 and 2010 according to a systematic review of the literature, while thousands of efficacy trials have been published that explore optimization of testing circumstances.
Studying treatment effects under idealized clinical trial conditions is attractive, but questions then remain over the generalizability of the findings to real-life circumstances.
Observational studies (performed in the thousands) are often precariously interpreted as able to answer questions about causal treatment effects. The use of routinely collected data is typically touted as being more representative of real life, but this is often not true. Most of the widely used observational studies deal with peculiar populations (e.g. nurses, physicians, or workers) and/or peculiar circumstances (e.g. patients managed in specialized health care systems or covered by specific insurance or fitting criteria for inclusion in a registry).
Eventually, observational studies often substantially overestimate treatment effects.
Useful research is patient centered. It is done to benefit patients or to preserve health and enhance wellness, not for the needs of physicians, investigators, or sponsors. Useful clinical research should be aligned with patient priorities, the utilities patients assign to different problems and outcomes, and how acceptable they find interventions over the period for which they are indicated. Value for money
Good value for money is an important consideration, especially in an era of limited resources.