Practical implementation of GCP
First of all, it is inevitable to understand the reasons why practical implementation of GCP principles still differs considerably from country to country. As summarized by Hartmann, M., Hartmann-Vareilles, F. (2006 in Kubiak, C. et al., 2009), only in the E.U. there are at least five Directives that govern clinical research, all of them were implemented by the Member States with great deal of interpretation.
Variability creates further major obstacles to clinical trials conduct in the developed countries, research and development costs as it is, and limited recruitment potential of these countries (Stankovski, L., Kubiak, C., Demotes-Mainard, J., 2009, p. 61). This is why, due to economic and regulatory considerations, epidemiological data, and/or in order to help the developing countries (further – DCs), a trend to move clinical trials to the DCs is evolving Hayasaka, E. (2005).
Of course, many would question quality of research that is conducted in the DCs, but evidence exists that overall understanding and implementation of GCP concepts in many of such countries is of high quality (Dent, N.J., 2000). The reasons why GCP principles are implemented in different ways vary between the developed and the developing countries. Whereas the first group has equally strong, though technically varying in details, policies protecting participants, the certain problems implicit in the latter group can compromise both trial subjects’ interests and data quality, among them (The European Group on Ethics in Science and New Technologies (EGE), 2003, pp. 9-12): economic conditions and regulatory environment.
So, what are the cons/pros of possible variations of the main principles (EGE, 2003 and ICH, 1996)?
- Respect for human dignity vs. exploitation: no variations acceptable, trials in DCs can be justified if: a) certain diseases are more typical of these countries, b) IP is intended for further marketing there, c) population will be further provided with the IP proven to be effective.
- Review and approval of study documents by the IRB/IEC: if no adequate IRB/IEC exists, no trial may be initiated. But in cases when local ECs are not present or are inadequate, central EC may decide for the country. Sometimes, advice of international ECs and community leaders are inevitable for successful trial, as values can differ considerably in the developed countries and ROW.
- Free will: right to consent/withdraw must be always respected, but populations in DCs are more vulnerable due to poverty, illiteracy, scarce resources. What is normal for developed countries may lead to exploitation of poor people. To improve this, independent observers should always be present during informed consent process.
- Equality: use of certain procedures/ placebo/ worse comparator medications must be exceptional and justified, i.e. allowed only in situations when no other treatment exists, a cheaper drug is developed for DCs, risks are minimal.
- Training and medical care standards: all staff must be adequately trained without exceptions. This is responsibility of sponsors to provide adequate training to local investigators and staff. Besides, though local care standards may be different, they are not necessarily detrimental to patients. However, all study-specific documents should account for local economic and cultural peculiarities in order not to waste resources while putting at risk study participants.
Any variations are acceptable only if the main principle remains unchanged: standards protecting clinical trials participants cannot be made weaker under no circumstances, though ways should be found how to implement the equally protecting measures in challenging realities. Otherwise trial conduct must not be possible.
- Dent, N. J.(2000) ‘Is ICH Exportable Outside the European Union?’, Quality Assurance, 8: 1, pp. 19- 31 [Online]. Available from: http://dx.doi.org/10.1080/105294100753209165 (Accessed: 09 October 2010).
- Hayasaka, E. (2005) ‘Approaches Vary for Clinical Trials in Developing Countries’, JNCI J Natl Cancer Inst, 97 (19), pp. 1401-1403 [Online]. Available from: http://jnci.oxfordjournals.org/content/97/19/1401.full (Accessed: 08 October 2010).
- Kubiak, C. et al. (2009) ‘Common definition for categories of clinical research: a prerequisite for a survey on regulatory requirements by the European Clinical Research Infrastructures Network (ECRIN)’, Trials, 10:95 [Online]. Available from: http://www.trialsjournal.com/content/10/1/95 (Accessed: 08 October 2010).
- The European Group on Ethics in Science and New Technologies (2003) Ethical Aspects of Clinical Research in Developing Countries [Online]. Available from: http://ec.europa.eu/european_group_ethics/docs/avis17_en.pdf (Accessed: 10 October 2010).
- The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) (1996) Guideline for Good Clinical Practice E6(R1) [Online]. Available from: http://www.ich.org/LOB/media/MEDIA482.pdf (Accessed: 08 October 2010)
- Stankovski, L., Kubiak, C., Demotes-Mainard, J. (2009) ‘ECRIN: making multinational clinical trials in Europe easier’, EJHPP, Vol. 15/ 6, pp. 61-62 [Online]. Available from: http://ppme.eu/Publications/EJHP/EJHP-Practice/Previous-issues/EJHP-Practice-Vol.15-2009-Issue-6/Update/ECRIN-making-multinational-clinical-trials-in-Europe-easier (Accessed: 08 October 2010).