Obtaining valid laboratory data in clinical trials conducted in resource diverse settings: lessons learned from a microbicide phase III clinical trial.
BACKGROUND
Over the last decade several phase III microbicides trials have been conducted in developing countries. However, laboratories in resource constrained settings do not always have the experience, infrastructure, and the capacity to deliver laboratory data meeting the high standards of clinical trials. This paper describes the design and outcomes of a laboratory quality assurance program which was implemented during a phase III clinical trial evaluating the efficacy of the candidate microbicide Cellulose Sulfate 6% (CS) [1].


METHODS
In order to assess the effectiveness of CS for HIV and STI prevention, a phase III clinical trial was conducted in 5 sites: 3 in Africa and 2 in India. The trial sponsor identified an International Central Reference Laboratory (ICRL), responsible for the design and management of a quality assurance program, which would guarantee the reliability of laboratory data. The ICRL provided advice on the tests, assessed local laboratories, organized trainings, conducted supervision visits, performed re-tests, and prepared control panels. Local laboratories were provided with control panels for HIV rapid tests and Chlamydia trachomatis/Neisseria gonorrhoeae (CT/NG) amplification technique. Aliquots from respective control panels were tested by local laboratories and were compared with results obtained at the ICRL.


RESULTS
Overall, good results were observed. However, discordances between the ICRL and site laboratories were identified for HIV and CT/NG results. One particular site experienced difficulties with HIV rapid testing shortly after study initiation. At all sites, DNA contamination was identified as a cause of invalid CT/NG results. Both problems were timely detected and solved. Through immediate feedback, guidance and repeated training of laboratory staff, additional inaccuracies were prevented.


CONCLUSIONS
Quality control guidelines when applied in field laboratories ensured the reliability and validity of final study data. It is essential that sponsors provide adequate resources for implementation of such comprehensive technical assessment and monitoring systems.


BACKGROUND
ClinicalTrials.gov NCT00153777 and Current Controlled Trials ISRCTN95638385.
HIV/STI Reference Laboratory, Institute of Tropical Medicine, Antwerp, Belgium. tcrucitti@itg.be
Tania
T
Crucitti
Katrien
K
Fransen
Rashika
R
Maharaj
Tom
T
Tenywa
Marguerite
M
Massinga Loembé
Kailapuri Gangatharan
KG
Murugavel
Kevin
K
Mendonca
Said
S
Abdellati
Greet
G
Beelaert
Lut
L
Van Damme
D000349:Africa; D000891:Anti-Infective Agents, Local / Q000627:therapeutic use*; D003906:Developing Countries; D006801:Humans; D007194:India; D011786:Quality Control
D000891:Anti-Infective Agents, Local