Pharmacogenetics
Using pharmacogenetics to improve existing medicines (continued)
Should all patients who are beginning treatment with warfarin receive a pharmacogenetic test? It is probably too early to make such a recommendation, as further research is required to validate these results. Moreover, the response to warfarin is not only determined by CYP2C9 but also by other metabolizing enzymes, and its interaction with other medicines. Research is required that takes account of all these factors before useful tests can be developed.18 It should also be noted that new medicines have been developed that are as effective as warfarin, but which have fewer adverse reactions associated with them, reducing the incentive to develop pharmacogenetic tests.19
3.24 These two examples illustrate the potential benefits of pharmacogenetic analysis concerning existing medicines. It is not clear, however, who would conduct such research. For medicines still under patent, the opportunity of a patent extension might encourage pharmaceutical companies to do so. Once medicines are no longer protected by patents, however, the pharmaceutical companies who produce them have little financial incentive to invest in efforts to refine their use, especially if this refinement means that fewer patients are advised to take the medicine. In addition, manufacturers of generic medicines have limited funds for investing in research and development. However, if pharmacogenetic tests for existing medicines could be patented, this may provide a sufficient incentive for companies to develop them (paragraphs 3.16 – 3.19). Moreover, several companies market diagnostic products which, while not covered by patent protection, are nevertheless profitable. As diagnostic companies generally invest relatively little in research and development, research to identify genetic variants influencing response to medicines would need to be funded by and undertaken in the public sector. It is by no means certain that research would successfully identify genetic variants which could form the basis of a clinically useful test. However, if such variants were identified, the diagnostic industry could then provide the expertise to make a standardised test.
3.25 One method of encouraging the application of pharmacogenetics to existing medicines would be to promote research into pharmacogenetics within the public sector. In particular, collaborative research programmes could be encouraged, which merge the expertise of researchers in genetics with the expertise of clinicians who collect and evaluate data regarding response to medicines. Collaborations with industry could also be beneficial, if researchers were able to share clinical data. Another strategy would be to promote dialogue between healthcare providers and the pharmaceutical industry to identify fruitful areas of research. In the UK, a similar process took place concerning meningitis C. Until recently, no vaccine was available for this disease. The NHS consulted with industry and expressed interest in purchasing a vaccine for the disease, which resulted in a vaccine being developed.20 This strategy could be beneficial on both a national and an international level.21
3.26 In conclusion, the application of pharmacogenetics to existing medicines may have the potential, in some cases, to improve their safety and efficacy. The Government has proposed that pharmacogenetic research will be of particular value for medicines which are commonly used, for medicines which are used in otherwise healthy people, or for the examination of serious adverse reactions which occur in response to a number of different types of medicine.22 We suggest that other relevant factors will include the scale of the negative effects experienced, the size of the patient population, the likely clinical value of the pharmacogenetic test and the existence of other treatments. It is not clear that the private sector will be motivated to pursue pharmacogenetic research in relation to medicines not covered by patent protection. We therefore recommend that efforts should be made to encourage pharmacogenetic research on existing medicines, where there is reason to believe that such research could significantly improve efficacy or safety. Funding and support should be made available within the public sector and public–private partnerships encouraged. We welcome the recent announcement by the Department of Health that £4 million will be directed towards research in pharmacogenetics over the next three years.23
Footnotes18 Pirmohamed M and Park BK (2001) Genetic susceptibility to adverse drug reactions, Trends Pharmacol Sci 22: 298-305.
19 There is also some suggestion that pharmacogenetics could be useful in predicting which patients are likely to respond well to the use of statins for preventing cardiovascular disease. See Humma LM and Terra SG (2002) Pharmacogenetics and cardiovascular disease: impact on drug response and applications to disease management, Am J Health Syst Pharm 59: 1241- 52; Winkelmann B (2002) Lipid lowering responses modified by genetic variation, in Pharmacogenomics: The Promise and Reality of Individualized Treatment, 17-18 October, Paris.
20 For example, see Trotter CL, Ramsay ME and Kaczmarski EB (2002) Meningococcal serogroup C conjugate vaccination in England and Wales: coverage and initial impact of the campaign, Commun Dis Public Health 5: 220-5. 21 Public-private partnerships have been developed in recent years in relation to neglected diseases affecting developing countries, for example, the International AIDS Vaccine Initiative, the Global TB Alliance and the Malaria Vaccine Initiative.
22 Department of Health (2003) Genetics White Paper. Our inheritance, our future – realising the potential of genetics in the NHS (Norwich: The Stationery Office, CM 5791), para. 5.21.
23 Department of Health (2003) Genetics White Paper. Our inheritance, our future – realising the potential of genetics in the NHS (Norwich: The Stationery Office, CM 5791).