Operational Challenges in Large Clinical Trials: Examples and Lessons Learned from the Gambia Pneumococcal Vaccine Trial

Abstract

The requirements for Good Clinical Practice (GCP) in clinical trials are well documented [1], and ethical issues are hotly debated [2].Operational aspects of trials, however, have received far less attention [3], perhaps due to restrictions on journal space for detailing methods.In low resource se t t i n g s, h o w e v e r , l a r g e t r i a l s often face many logistical and organizational obstacles, and thus the practical difficulties in running a trial to GCP standards should not be ignored.Here, we describe the main operational challenges to a randomized, double-blind, placebocontrolled trial of the safety and efficacy of pneumococcal conjugate vaccine among over 17,000 infants in the Gambia.The trial began in August 2000, and after the magnitude of the challenges were recognized, a new senior principal investigator (FTC) and project manager (FGY) were recruited, taking up post in June 2001.We summarize here the major lessons learnt in trial implementation in a resource-poor setting. Overview of Trial Preparation and Study MethodsThe trial was conducted in Upper and Central River Divisions of the Gambia, covering an area of about 5,000 km 2 , b i s e c t e d b y t h e r i v e r G a m b i a .Government mother-child health (MCH) services are provided at 15 fixed facilities, the two largest being Bansang hospital in the Central River Division and Basse health centre in the Upper River Division, and about 100 additional outreach sites.The Medical Research Council (MRC) main station is in Fajara, 380 km from Basse.The journey between them took 5 hours in 2000 when the trial began, and, due to deteriorating road