Are concomitant treatments confounding factors in randomized controlled trials on intensive blood-glucose control in type 2 diabetes? a systematic review

BMC Med Res Methodol. 2013 Aug 30:13:107. doi: 10.1186/1471-2288-13-107.

Abstract

Background: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Antihypertensive Agents / pharmacology
  • Antihypertensive Agents / therapeutic use
  • Blood Glucose
  • Confounding Factors, Epidemiologic
  • Diabetes Complications / drug therapy
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Humans
  • Hypertension / drug therapy
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use
  • Observer Variation
  • Randomized Controlled Trials as Topic
  • Treatment Outcome

Substances

  • Antihypertensive Agents
  • Blood Glucose
  • Hypoglycemic Agents