Pharmacogenetics
Introduction
1.1 People vary in their response to the same medicine. Few medicines are effective for everyone;
all may cause adverse reactions or, occasionally, death. Some of the variation between individuals in response to medicines is due to differences in their genetic make-up. There are many different reasons why medicines may be dangerous or ineffective, such as inaccurate prescribing, poor compliance by the patient, and interaction between a particular medicine and other substances, including other medication. However, advances in genetic knowledge may enable us to take better account of differences between individuals. Pharmacogenetics is the study of genetic variation that affects response to medicines. It has the potential to play an important role in improving the safety and efficacy of medicines. (See Box 1.1 for definitions of terminology used in this Report).
1.2 The relevance of pharmacogenetics for the development and administration of medicines
was first recognised in the 1950s. In parallel with the significant advances in the study of the human genome in recent decades, pharmacogenetics is an expanding field of research. The option of using genetic information to predict response to medicines has led some to make the optimistic claim that the development of ‘personalised’ medicine, or ‘the right medicine, for the right patient, at the right dose’, is only a matter of time.
1.3 Such claims require careful assessment. Pharmacogenetics does have the potential to
improve the quality of patient care significantly. Conversely, delaying its introduction could harm patients, whether through lack of training and education or for reasons of practical constraint. At the same time, just how quickly and effectively this technology can be deployed is unclear. There are few current applications of pharmacogenetic testing, and we do not know to what degree possible applications of pharmacogenetics can be realised given the constraints imposed by the complexity of our response to medicines and the current systems of healthcare delivery. Several different factors will influence the proportion of patients who will come to benefit from pharmacogenetics, including economic influences on the pharmaceutical industry, regulatory frameworks applied by relevant authorities,
cost–benefit constraints of healthcare providers with limited budgets and the relationship between patients and physicians.
1.4 As with any new technology, the benefits of pharmacogenetics may be accompanied by unintended disadvantages. For example, the introduction of pharmacogenetics could lead to a further stratification of the market for medicines, discouraging pharmaceutical companies from developing medicines that would provide a significant benefit to only a small number of patients. The application of pharmacogenetics might impede healthcare delivery, by taking up a considerable amount of a clinician’s time in conducting the test and explaining the results. It might exacerbate inequities in medical provision. The extensive acquisition of genetic information that a wide-ranging programme of pharmacogenetics
would involve might also lead to violations of legitimate expectations of confidentiality and privacy, and unfair discrimination.
1.5 The aim of this Report is to give an account of the likely effect of pharmacogenetics on the design of medicines and on clinical practice and to highlight ethical, legal and regulatory issues that may be raised. Recommendations are made regarding decisions that will need to be taken if we are to derive the greatest benefit from the potential of these biomedical developments.
| There is a lack of agreement about the precise terminology to describe how genetic information is related to individuals’ responses to medicines. Various definitions of pharmacogenetics and pharmacogenomics have been put forward and the terms are sometimes used interchangeably. In this Report, we use the term ‘pharmacogenetics’ as follows: Pharmacogenetics: the study of the effects of genetic differences between individuals in their response to medicines. |
| These differences may or may not be related to the disease being treated. Research in pharmacogenetics involves comparing genetic data from individuals who have different responses to a medicine. |
| The term ‘pharmacogenomics’ is not distinctly differentiated from pharmacogenetics, but implies the examination of whole genomes or substantial numbers of genes in order, for example, to identify putative targets for medicines or to identify large-scale differences in the patterns of gene expression in response to chemical compounds. Pharmacogenetic test: a genetic test can be defined as a test to detect the presence or absence of, or change in, a particular gene or chromosome. * |
| This can be done directly, by analysing the chromosomes or DNA of an individual, or indirectly, by examining the products of their DNA, such as RNA or proteins (Appendix 1 explains in more detail how genes work). In some cases, the presence or absence of particular genes can be determined by consideration of the family history of an individual, or simply by clinical observation. In the context of pharmacogenetics, the same types of direct or indirect tests for a gene sequence or gene product are applied to test for response to a medicine. We use the term pharmacogenetic test to refer to both types of test. A pharmacogenetic test might examine inherited DNA or somatic mutations in DNA (see paragraphs 2.6-2.10). An important aim of pharmacogenetics is the improvement of the safety of medicines. There is a range of terminology to refer to the negative or unintended consequences of administering a medicine. In this Report, we use the term adverse reaction to refer to an untoward medical occurrence caused by and arising after the administration of a medicine under normal conditions of use. |
| * Advisory Committee on Genetic Testing (1997) Code of Practice and Guidance on Human Genetic Testing Services Supplied Direct to the Public (London: Health Departments of the United Kingdom). |
| † A related term is ‘adverse event’, which describes any untoward medical occurrences arising after the administration of a medicine. Adverse events may be an adverse reaction to the medicine, but they may also be conditions arising independently of the medicine. |