What’s Wrong with Non-regulated Interventions & Trials?

Question Mark, BubbleThe following article (written by Rafeal Dal-Re, Michael Bracken & John Ioannidis in the BMJ) is a timely reminder to authors, journalists and consumers about the pros and cons of non-regulated interventions and trials.

Efforts to promote the availability of data from clinical trials have been led predominantly by regulators (EMA, 2014) or drug companies (Doshi et al., 2013) and tend to focus on regulated interventions – that is, drugs, biologics, and medical devices.

By contrast, trials of non-regulated interventions such as diets, exercise programmes, physiotherapy, surgical procedures, behavioural interventions, or complementary medicine have received much less attention.

Professional (3), Best PracticeTo determine the benefits and harms of an intervention, randomised trial evidence is needed. These trials should be registered and published in an accurate and unbiased manner.

Ideally clinical trial protocols and raw data should be made available to ensure transparency and for further use – for example, in individual patient data meta-analyses. These imperatives are well appreciated for trials of regulated interventions, but practices are lagging for non-regulated interventions.

BullshitAll of us are likely to experience one or more non-regulated intervention in our lives. Yet many trials in these fields are small, underpowered, and lack quality safeguards such as appropriate randomisation, blinding, or choice of placebo or sham control (Agha et al., 2007). The results are often spurious.

Very large, well conducted, trials on non-regulated interventions are rare, even for common lifestyle interventions such as diet and exercise programmes (Estruch et al., 2013; Jorgensen et al., 2014) Some trials of non-regulated interventions such as surgical procedures and behavioural interventions have intrinsic difficulties in their conduct (IMPROVE, 2014; Wilis et al, 2006), such as how to standardise the intervention. Non-standardisation leads to more heterogeneity and potential for bias.

Read the rest of the article at: http://www.bmj.com/content/350/bmj.h1323


EMA (European Medicines Agency). (2014) European Medicines Agency Policy on Publication of Clinical Data for Medicinal Products for Human Use. Oct 2014. ww.ema.europa.eu/docs/en_GB/document_library/Other/2014/10/WC500174796.pdf.

Doshi, P,, Goodman, S.N., & Ioannidis, J.P. (2013) Raw Data from Clinical Trials: Within Reach? Trends Pharmacol Sci 2013. 34, PP.645-7.

Agha, R,, Cooper, D, & Muir, G. (2007) The Reporting Quality of Randomised Controlled Trials in Surgery: A Systematic Review. International Journal of Surgery. 5, pp.413-422.

Estruch, R,, Ros, E,, Salas-Salvadó, J, et al. (2013) Primary Prevention of Cardiovascular Disease with a Mediterranean Diet. New England Journal of Medicine. 368, pp.1279-1290.

Jørgensen, T,, Jacobsen, R.K,, Toft, U,, Aadahl, M,, Glümer, C, & Pisinger, C. (2014) Effect of Screening and Lifestyle Counselling on Incidence of Ischaemic Heart Disease in General Population: Inter99 randomised trial. BMJ 2014;348:g3617.

IMPROVE Trial Investigators. (2014) Endovascular or Open Repair Strategy for Ruptured Abdominal Aortic Aneurysm: 30 Day Outcomes from IMPROVE Randomised Trial. BMJ 2014;348:f7661.

Willis, S.L., Tennstedt, S.L., Marsiske M., et al. (2006) Long-term Effects of Cognitive Training on Everyday Functional Outcomes in Older Adults. Journal of the American Medical Association. 296, pp.2805-2814.

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