Tag Archives: Clinical trial

Subgroup analyses

11 Dec

Heterogeneity in treatment effects

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Subgroup analysis is the core of interpretation of random controlled trials. But it must respect some strictly defined rules otherwise it will lead the reader to dangerous misinterpretation. A recent article (2010) by Kent et al exposes a very useful checklist for authors as well as for readers.

A given treatment induces a 25% Relative Risk Reduction of a given disease; a subgroup analysis implemented on one hand in a low risk of disease group of subjects versus in an other hand in a high risk of disease group of subjects will lead to an Absolute Risk Reduction of 1% versus 5% and a number of subjects needed to treat to prevent one additional disease of 100 versus 20. What is at stakes for health policy decision makers, care providers and patients is no less than efficacy, efficiency and harms of treatments grounded on evidence based results.

In their open access article the authors, from the Institute for Clinical Research and Health Policy Studies (Boston, MA, USA) and from the Center for statistics in Medicine (University of Oxford, UK) and from the department of Hygiene and Epidemiology (Ioannini, Greece) clearly expose the advantages and limits of the subgroup analysis techniques, weather they aim at exploratory research without immediate clinical implication or they attempt to further confirm an already strong a priori pathophysiological or empirical knowledge.

According to those authors, for reporting on subgroup analysis and heterogeneity in treatment effects, health services authors should:

Evaluate the distribution of the risk of disease in the overall study population before any treatment using a pre-specified externally developed risk prediction model (eg: risk score).

Pre-specify the subgroups including the threshold values for continuous or ordinal variables (except for clearly labelled exploratory purposes which are potentially useful for hypothesis generation and informing future research but having little or no immediate relevance to patient care).

Report the statistical significance between subgroups using interaction terms (testing for the significance of a treatment effect within a subgroup is inappropriate due to poor statistical power).

Correct the statistical comparisons for the number of the number of primary subgroup analysis performed.

The full text of the entire article is available in open access here.

Cite this article as: Kent et al.: Assessing and reporting heterogeneity in
treatment effects in clinical trials: a proposal. Trials 2010 11:85

beta blockers

25 Nov
some β1-selective beta blockers: Atenolol, Bis...

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“we do a large trial and discover that, rather than preventing, we are causing”

This is the sentence written by searchers when disseminating their results. The Beta blockers in preventive use for patients who undergo surgery may have cause more harm than benefits. The searcher who first discovered their preventive effect has been fired from his university for fictitious data use and failure to obtain patient consent. Furthermore  a randomized controlled trial shows an increase of overall mortality associated with Beta blockers systematic perioperative  use. Like earlier for the menopausal hormonal replacement therapy, wide randomized controlled trials lead to reconsider previous beliefs in preventive effects. Any way, medical research has to continue in the sound interest of patients.

subgroup analysis can lead to jail

8 Nov

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A scientist that undertook a subgroup analysis passed nearby a prison sentence in the US.

W. Scott Harkonen have been convinced of false dissemination and misleading statement for his interpretation by subgroup analysis of  a clinical trial results.  He is accused by the Feds of manipulating the data with a subgroup analysis such modifying the primary endpoint of the trial. The following dissemination of the results he obtained provoked a wide off label prescription of the drug tested in the trial. The consequences were inappropriate spending for Medicaid and Medicare. The cost of off label prescription for one patient-year was approximately $50,000. This cost is proportional to the severity of the sentence pronounced by the judge. Pharmalot reported this lawsuit in several posts, the last report being available here.


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