The WHO and ICH (International Conference for Harmonization) GCP codes have not been updated since 1995 and 1996 respectively. Currently, a partial revision of the ICH GCP code is ongoing, but the update process does not seem sufficiently inclusive. If GCP codes are meant to set standards pertinent and applicable at global level, then a more comprehensive revision is needed, characterized by more transparency and more inclusiveness together with adequate representation of researchers, sponsors, regulators and ethical reviewers from LMICs
by Raffaella Ravinetto*
Head of Clinical Trials Unit, Antwerp Institute of Tropical Medicine
The international Good Clinical Practices Code: Time for a Global Approach
The Good Clinical Practices (GCP) codes are meant to set globally applicable standards for the conduct of clinical trials on pharmaceutical products on human subjects (1). They are “an international ethical and scientific quality standard for designing, conducting, recording and reporting trials that involve the participation of human subjects”. Compliance with GCP “provides public assurance that the rights, safety and well-being of trial subjects are protected, consistent with the principles that have their origin in the Declaration of Helsinki, and that the clinical trial data are credible” (2).
There are two international GCP codes: the one of the World Health Organization (WHO) (1) and the one of the International Conference of Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) (2). Despite their similarities, they originate from quite different frameworks. The WHO is an international organization that brings together 194 Member States, and it is mandated to direct and coordinate international health within the United Nations system (http://www.who.int/about/en/). The ICH brings together the regulatory authorities and pharmaceutical industry from the European Union, the United States, Japan, Canada and Switzerland, and it is mandated “to improve, through harmonisation, the efficiency of the process for developing and registering new medicinal products in the form of the International Conference on Harmonisation of technical requirements for registration of pharmaceuticals for human use” (http://www.ich.org/home.html). Despite its limited mandate, the ICH has the ambition to become a global standard, and today most clinical research actors in Low- and Middle-Income Countries (LMICs) refer to the ICH rather than WHO GCP code. Non-ICH countries are involved in ICH through the Global Cooperation Group, but in practice their contribution seems to be quite limited (3),
Early critics of the ICH GCP code contended that it derived from informal consensus (considered as the weakest approach to guidelines development) and that it was written in absence of a systematic up-to-date search for the relevant literature (4). Others argued that the international GCP codes were “created by a small number of regulatory agencies and drug companies from industrialized nations, with little input from developing countries” (5). Leading academic researchers also contended that the international GCP codes lack consideration for the challenges met by clinical researchers in LMICs (6, 7). The latter is not surprising. While other guidelines and regulations are subject to periodical revisions, the WHO and ICH GCP codes have not been updated since 1995 and 1996 respectively. Thus, they reflect the situation of more than twenty years ago, when multi-centre clinical trials were mainly conducted in Western contexts, and they do not take into account the challenges met today, in the context of “globalization of clinical trials”, with more and more trials carried out in LMICs (8). Since the international GCP codes guide and orient most national legislators and most funding agencies, their failure to address the challenges of researchers in LMICs may result in insufficient protection of research subjects and communities in these contexts.
We are not aware of any update of WHO GCP. Conversely, a partial revision of the ICH GCP code is ongoing, to modernize it “by supplementing with additional recommendations which will facilitate broad and consistent international implementation of new methodologies” (http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E6/E6_R2__Addendum_Step2.pdf). The fact that the revision was accompanied by an open consultation (till 31st January 2016) surely provided a positive opportunity to try to have an impact. But the update process was poorly known and it does not seem sufficiently inclusive. In practice, it is not clear whether significant inputs came from the non-ICH region, and to what extent they will be taken into account.
If GCP codes are meant to set standards pertinent and applicable at global level, then a more comprehensive revision is needed, characterized by more transparency and more inclusiveness. In particular, adequate representation of researchers, sponsors, regulators and ethical reviewers from LMICs should be ensured. The revised guidelines should be strongly rooted in ethics, be sensitive to the different cultural and social perspectives, and take into account trials- and context-related challenges, for being at the same time “global”, “context centered” and “patient centered”.
This paper derives from a doctoral thesis, “Methodological and ethical challenges in non-commercial North-South collaborative clinical trials”, carried out at KU Leuven (Belgium). The manuscript is available at https://lirias.kuleuven.be/handle/123456789/517274.
1) World Health Organization (WHO). Guidelines for Good Clinical Practices for trials on pharmaceutical products. 1995. WHO Technical Report Series No. 850, Annex 3. Geneva, Switzerland. Last accessed on 14/09/2015 at http://apps.who.int/medicinedocs/pdf/whozip13e/whozip13e.pdf
2) International Conference of Harmonization (ICH). ICH Tripartite Guideline for Good Clinical Practices E6 (R1), 10th June 1996. Last accessed on 14/09/2015 at http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E6/E6_R1_Guideline.pdf
3) Specht S and Klingmann I. ICH: strenghts, weaknesses, and future tasks. Ther Inn & Reg Science 2014; 48(3):357-61
4) Grimes DA, Hubacher D, Nanda K, Schulz KF, Moher D and Altman DG. The Good Clinical Practice guideline: a bronze standard for clinical research. Lancet 2005; 366(9480):172-4
5) Rennie S. The FDA and Helsinki. Hastings Cent Rep 2009: 39(3):49
6) White NJ. Editorial: Clinical trials in tropical diseases: a politically incorrect view. Trop Med Int Health 2006; 11(10):1483-4
7) Lang T, Cheah P Y and White N J. Clinical research: time for sensible global guidelines. Lancet 2011; 377(9777):1553–5
8) Lang T and Siribaddana S. Clinical trials have gone global: is this a good thing? PLoS Med 2012; 9(6):e1001228
*Raffaella Ravinetto holds a Pharmacy Degree from the University of Torino and a Postgraduate Diploma in Tropical Medicine from the Antwerp Institute of Tropical Medicine.
After a seven-year experience as a Clinical Research Scientist in the private pharmaceutical sector, she worked in emergency and development programs in the Balkans and in Africa. In 2002, she joined Médecins Sans Frontières (MSF), where she followed various dossiers on access to essential medicines and quality of medicines, while performing regular field assessments. She currently works at the Antwerp Institute of Tropical Medicine, as head of the Clinical Trials Unit, coordinator of the Switching the Poles Clinical Research Network and promoter of Quamed (a Network promoting evidence-based strategies for universal access to quality medicines). She was president of the Italian branch of MSF (2007-2011).
Her main areas of interest include North-South collaborative clinical research, research ethics (particularly in relation to resource-constrained settings) and access to health.