Departures from the protocol during conduct of a clinical trial: a pattern from the data record consistent with a learning curve.

Abstract

OBJECTIVE:

Recognition of learning curves in medical skill acquisition has enhanced patient safety through improved training techniques. Clinical trials research has not been similarly scrutinised. The VALsartan In Acute myocardial iNfarcTion, a large multinational, pragmatic, randomised, double-blind, multicentre trial, was retrospectively evaluated for evidence of research conduct consistent with a performance "learning curve".

DESIGN:

Records provided protocol departure (deviations/violations) and documentation query data. For each site, analysis included patient order (eg, first, second), recruitment rate and first enrollment relative to study start date.

SETTING:

Computerised data from a trial coordinated by an academic research organisation collaborating with 10 academic and 2 commercial research organisations and an industry sponsor. Interventions 931 sites enrolled 14,703 patients. Departures were restricted to the first year. Exclusions included patient's death or loss to follow-up within 12 months and subjects enrolled 80th or higher at a site. Departures were assessed for variance with higher patient rank, more frequent recruitment and later start date.

METHODS AND RESULTS:

12,367 patients at 931 sites were analysed. Departures were more common for patients enrolled earlier at a site (p<0.0001). For example, compared with the 30th patient, the first had 47% more departures. Departures were also more common with slower enrollment and site start closer to the trial start date (p<0.0001). Similar patterns existed for queries.

CONCLUSIONS:

Research performance improved during the VALsartan In Acute myocardial iNfarcTion consistent with a "learning curve". Although effects were not related to a change in outcome (mortality), learning curves in clinical research may have important safety, ethical, research quality and economic implications for trial conduct.

• Authors: J M Taekman, M Stafford-Smith, E J Velazquez, M C Wright, B G Phillips-Bute, M A Pfeffer, M A Sellers, K S Pieper, M F Newman, F Van de Werf, R Diaz, J Leimberger, R M Califf
• Journal: Quality & safety in health care (Qual Saf Health Care) Vol. 19 Issue 5 Pg. 405-10 (Oct 2010) ISSN: 1475-3901 [Electronic] England
• PMID: 20702441 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Topics

• Clinical Protocols
• Guideline Adherence
• Humans
• Learning Curve
• Multicenter Studies as Topic
• Randomized Controlled Trials as Topic
• Retrospective Studies