Development of a checklist of quality indicators for clinical trials in resource-limited countries: The French National Agency for Research on AIDS and Viral Hepatitis (ANRS) experience

Abstract

Background

Since 1994, the French National Agency for Research on AIDS and Viral Hepatitis (ANRS) has funded research sites in resource-limited countries (RLCs). These sites implement research on human immunodeficiency virus (HIV) infection and Hepatitis C. In parallel, international regulations and recommendations for clinical trials have evolved and proliferated. However, little guidance exists on how these should be interpreted and applied within academic trials and in the context of RLCs. After developing a specific Ethical Charter for research in developing countries in 2002, ANRS developed a set of quality indicators (QIs) as a monitoring tool for assessing compliance to international guidelines.

Purpose

We describe here the development process, QIs adopted, and areas for improvement.

Methods

In 2008, a group of experts was convened that included a researcher representing each ANRS site (Cote d’Ivoire, Senegal, Cameroun, Burkina Faso, Egypt, and Cambodia). Our structuring interaction development process combined evidence and expert opinion in two nominal group meetings to identify (1) clinical trial processes involved, (2) issues specific to RLCs in terms of Good Clinical Practice (GCP) and the application of ethical recommendations, and (3) checklists of QIs adapted to clinical trials conducted in RLCs.

Results

The trial process reviewed and proposed for RLCs was mostly similar to the one produced in wealthier countries. The scheme generated by our work group added two further processes: ‘drug management’ and ‘biological investigations’. Specific issues regarding trial management in RLCs were therefore described for eight trial steps (1) protocol conception and seeking authorizations, (2) participant enrollment and follow-up, (3) site monitoring, (4) drug management, (5) biological investigations, (6) record management, (7) data management, and (8) site closeout. A total of 58 indicators were identified with at least one indicator for each trial process.

Limitations

Some trial activities require further consideration, that is, in the case of vulnerable participants (children, pregnant women). Proposed indicators are the result of expert consensus and reflect their experience in the HIV field. Relevance to existing trials and extrapolation to other fields must be assessed.

Conclusions

This innovative program allowed ANRS sites located in RLCs to share their GCP implementation experiences in order to build a list of relevant indicators for clinical trials. The next step is to collect data from ongoing HIV and hepatitis C trials in these settings and will assess the relevance of these indicators to document current quality of performance among trials in resource-limited settings.

Get full access to this article

View all access options for this article.

References

Anglaret

Chene

Attia

. Early chemoprophylaxis with trimethoprim-sulphamethoxazole for HIV-1-infected adults in Abidjan, Cote d’Ivoire: A randomised trial. Cotrimo-CI Study Group. Lancet 1999; 353(9163): 1463–68.

Laurent

Kouanfack

Koulla-Shiro

. Effectiveness and safety of a generic fixed-dose combination of nevirapine, stavudine, and lamivudine in HIV-1-infected adults in Cameroon: Open-label multicentre trial. Lancet 2004; 364(9428): 29–34.

Dabis

Msellati

Meda

. 6-month efficacy, tolerance, and acceptability of a short regimen of oral zidovudine to reduce vertical transmission of HIV in breastfed children in Cote d’Ivoire and Burkina Faso: A double-blind placebo-controlled multicentre trial. DITRAME Study Group. DIminution de la Transmission Mere-Enfant. Lancet 1999; 353(9155): 786–92.

Nagot

Ouedraogo

Foulongne

. Reduction of HIV-1 RNA levels with therapy to suppress herpes simplex virus. N Engl J Med 2007; 356(8): 790–99.

ANRS. Ethics Charter for Research in Developing Countries. ANRS, Paris, 2008. Available at: http://www.anrs.fr/content/download/2804/16200/file/charte_ethiqueAngl2008.pdf

ICH. International conference on harmonisation of technical requirements for registration of pharmaceuticals for human use: Harmonised tripartite guideline – ICH topic E6 (R1), 1996. Available at: http://www.ich.org/products/guidelines/efficacy/article/efficacy-guidelines.html

CIOMS. Lignes directrices internationales d’éthique pour la recherche biomédicale impliquant des sujets humains. Genève, 2003. Available at: http://www.cioms.ch/publications/guidelines/french_text.htm

Krleza-Jeric

Lemmens

7th revision of the Declaration of Helsinki: Good news for the transparency of clinical trials. Croat Med J 2009; 50(2): 105–10.

Lang

White

Tran

. Clinical research in resource-limited settings: Enhancing research capacity and working together to make trials less complicated. PLoS Negl Trop Dis 2010; 4(6): e619.

10.

Vray

Simon

Bompart

Guidelines for clinical research in developing countries. Therapie 2007; 62(3): 217–27.

11.

Bompart

Hirsch

Bertoye

Vray

Good clinical practice in developing countries: Applying recommendations. Therapie 2008; 63(2): 83–88, 77–82.

12.

European Medicines Agency (EMA). Inspection procedures and guidance for GCP inspections conducted in the context of the centralised procedure. EMEA, London, March 2009. Available at: http://www.emea.europa.eu/Inspections/GCPproc.html

13.

Marwah

Van de Voorde

Parchman

Good clinical practice regulatory inspections: Lessons for Indian investigator sites. Perspect Clin Res 2010; 1(4): 151–55.

14.

European Medicines Agency (EMA). Mandate, objectives and rules of procedure for the GCP Inspectors Working Group (GCP IWG). EMEA, London, July 2007. Available at: http://www.ema.europa.eu/Inspections/docs/23948607en.pdf

15.

Lorenzo

Garrafa

Solbakk

Vidal

Hidden risks associated with clinical trials in developing countries. J Med Ethics 2010; 36(2): 111–15.

16.

World Medical Association (WMA). Declaration of Helsinki – Ethical principles for medical research involving human subjects, 2008. Available at: http://www.wma.net/en/30publications/10policies/b3/

17.

Metrics Champion Consortium. Clinical trial performance metrics. Carmel, IN: Metrics Champion Consortium, May 2009. Available at: http://www.metricschampion.org/

18.

Murphy

Black

Lamping

. Consensus development methods, and their use in clinical guideline development. Health Technol Assess 1998; 2(3): i–iv, 1–88.

19.

Zeh

Inzaule

Magero

. Field experience in implementing ISO 15189 in Kisumu, Kenya. Am J Clin Pathol 2010; 134(3): 410–18.

20.

Fitzgerald

Marotte

Verdier

Johnson

Jr Pape

JW.

Comprehension during informed consent in a less-developed country. Lancet 2002; 360(9342): 1301–02.

21.

Chêne

‘AC5’ eca. Les indicateurs de qualité des centres cliniques de l’ANRS. In 6e seminaire de recherche clinique sur l’infection par le VIH, Intervention thérapeutiques au nord et au sud: questions croisées (ed Pasteur

), 1 et 2 avril, ANRS, Institut Pasteur, Paris, 2004, pp. 17–20.

22.

Grimes

Hubacher

Nanda

. The good clinical practice guideline: A bronze standard for clinical research. Lancet 2005; 366(9480): 172–74.