Are concomitant treatments confounding factors in randomized controlled trials on intensive blood-glucose control in type 2 diabetes? a systematic review
1 Département de Médecine Générale, Université Claude Bernard Lyon 1, Lyon F-69008, France
2 UMR 5558, Laboratoire de Biométrie et Biologie Evolutive, CNRS, Université Claude Bernard Lyon 1, Villeurbanne F-69100, France
3 Service de Pharmacologie Clinique, Centre Hospitalier Régional et Universitaire de Tours, Tours, France
4 UMR 7292, CNRS, Université François Rabelais, Tours, France
5 Clinical Investigation Centre, INSERM CIC201, Louis Pradel Hospital, Bron 69500, France
6 Hospices Civils de Lyon, Service de Pharmacologie Clinique, Hôpital Louis Pradel, Bron 69500, France
BMC Medical Research Methodology 2013, 13:107 doi:10.1186/1471-2288-13-107Published: 30 August 2013
Open-label, randomized controlled trials (RCTs) are subject to observer bias. If patient management is conducted without blinding, a difference between groups may be explained by other factors than study treatment. One factor may come from taking concomitant treatments with an efficacy on the studied outcomes. In type 2 diabetes, some antihypertensive or lipid-lowering drugs are effective against diabetic complications. We wanted to determine if these concomitant treatments were correctly reported in articles of RCTs on type 2 diabetes and if they might have influenced the outcome.
We performed a systematic review using Medline, Embase, and the Cochrane Library (from January 1950 to July 2010). Open-label RCTs assessing the effectiveness of intensive blood-glucose control in type 2 diabetes were included. We chose five therapeutic classes with proven efficacy against diabetes complications: angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor antagonists (AIIRAs), fibrates, statins, and aspirin. Differences between concomitant treatments were considered statistically significant when p < 0.05.
A total of eight open-label RCTs were included, but only three (37.5%) of them published concomitant treatments. In two studies (ACCORD and ADVANCE), a statistically significant difference was observed between the two groups for aspirin (p = 0.02) and ACEIs (p = 0.02).
Few concomitant treatments were published in this sample of open-label RCTs. We cannot completely eliminate an observer bias for these studies. This bias probably influenced the results to an extent that has yet to be determined.