An IV for the RCT: using instrumental variables to adjust for treatment contamination in randomised controlled trials
Open Access
- 4 May 2010
- Vol. 340 (may04 2), c2073
- https://doi.org/10.1136/bmj.c2073
Abstract
Although the randomised controlled trial is the “gold standard” for studying the efficacy and safety of medical treatments, it is not necessarily free from bias. When patients do not follow the protocol for their assigned treatment, the resultant “treatment contamination” can produce misleading findings. The methods used historically to deal with this problem, the “as treated” and “per protocol” analysis techniques, are flawed and inaccurate. Intention to treat analysis is the solution most often used to analyse randomised controlled trials, but this approach ignores this issue of treatment contamination. Intention to treat analysis estimates the effect of recommending a treatment to study participants, not the effect of the treatment on those study participants who actually received it. In this article, we describe a simple yet rarely used analytical technique, the “contamination adjusted intention to treat analysis,” which complements the intention to treat approach by producing a better estimate of the benefits and harms of receiving a treatment. This method uses the statistical technique of instrumental variable analysis to address contamination. We discuss the strengths and limitations of the current methods of addressing treatment contamination and the contamination adjusted intention to treat technique, provide examples of effective uses, and discuss how using estimates generated by contamination adjusted intention to treat analysis can improve clinical decision making and patient care.Keywords
This publication has 33 references indexed in Scilit:
- On estimating treatment effects under non‐compliance in randomized clinical trials: are intent‐to‐treat or instrumental variables analyses perfect solutions?Statistics in Medicine, 2006
- Drug Copayment and Adherence in Chronic Heart Failure: Effect on Cost and OutcomesPharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 2006
- A new preference-based analysis for randomized trials can estimate treatment acceptability and effect in compliant patientsJournal of Clinical Epidemiology, 2006
- Estimating the Effect of Smoking Cessation on Weight Gain: An Instrumental Variable ApproachHealth Services Research, 2006
- A meta-analysis of the association between adherence to drug therapy and mortalityBMJ, 2006
- Calcium plus Vitamin D Supplementation and the Risk of FracturesNew England Journal of Medicine, 2006
- Adherence to candesartan and placebo and outcomes in chronic heart failure in the CHARM programme: double-blind, randomised, controlled clinical trialThe Lancet, 2005
- Estimating treatment effects from randomized clinical trials with noncompliance and loss to follow-up: the role of instrumental variable methodsStatistical Methods in Medical Research, 2005
- Better reporting of randomised controlled trials: the CONSORT statementBMJ, 1996
- Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S)The Lancet, 1994