Pharmacogenetics
Legal incentives
3.7 Legal obligations may be more stringent than the requirements set out by regulators. Successful litigation against companies who manufacture medicines would have an impact on the status of pharmacogenetic testing in clinical trials. Claims against the manufacturers of medicines by patients who have suffered adverse events can be advanced on two legal bases: fault liability (negligence) and strict liability. Claims in negligence relate to the obligation to take reasonable care and are often based on arguments that the manufacturer failed to carry out adequate research with regard to the medicine, and therefore failed to provide proper information about the risks associated with the product, and the balance between the risks and benefits, which could have been detected by such research. Thus, claims could arise from the occurrence of adverse effects, or from the failure of a manufacturer to provide information about patients for whom a medicine is likely to be of little or no benefit. Health professionals and health authorities can also be sued in negligence (see paragraphs 5.25 – 5.28).
3.8 Claims based on strict liability, which are normally limited to manufacturers of medicines, concern only the nature of the product: the reasonableness of the manufacturer’s conduct is not the focus of the inquiry. However, if a medicine is not found to offer the safety that patients generally are entitled to expect, taking account of the warnings supplied in the product information and other relevant circumstances, the product is treated as ‘defective’ and manufacturers may be found liable for the adverse reactions caused. This may be because the research conducted during clinical trials was not sufficient to identify the adverse reaction, or because information about potential risks and benefits for particular groups of patients was not passed on. In the UK, manufacturers can mount the ‘development risk defence’ to argue that even though a medicine was defective, the problem could not have been identified at the time the medicine was supplied because the state of scientific and technical knowledge was not sufficiently advanced. In cases of negligence and of strict liability, having met the relevant regulatory requirements is not a sufficient defence. Courts may decide that additional research or activity was reasonable, or, for strict liability purposes, practical, in a particular case.
3.9 Regarding claims in negligence, claimants might argue that pharmacogenetic testing should be part of any ‘reasonable’ research into the development of a new medicine, since it has the potential to identify groups of patients who may be adversely affected or who will not benefit from the medicine. Likewise, in terms of strict liability, a failure to carry out such research when it is practicable to do so may render ineffective the ‘development risk defence’. However, such an argument assumes that pharmacogenetics will be relevant for every new medicine that is developed. For medicines such as Herceptin, which are based on the genetic characteristics of a diseased tissue, pharmacogenetic testing is clearly an integral aspect of the process of development. In other cases, there might be no immediate reason to believe that genetic variation will play a sufficiently significant role in determining efficacy or safety to warrant pharmacogenetic analysis. In such cases, it could be that pharmaceutical companies collect genetic data in case problems arise in the future, but do not examine the data unless and until such problems become apparent.
3.10 The storage of blood and tissue samples from participants in clinical trials for extended periods of time is currently common practice. Such collection without testing could be problematic if a medicine is subsequently found to cause serious adverse reactions or to be ineffective in a number of patients and these characteristics could have been detected by pharmacogenetic testing. Having taken the samples, it could be argued by claimants that it was negligent not to conduct pharmacogenetic analysis in relation to such samples and to issue warnings that reflected the results of such research. In the context of strict liability, the same proposition translates into the argument that, in the absence of such warnings, the product was defective and the defective nature of the product was discoverable through recognised research techniques. However, the developers of medicines will be likely to argue that, unless there is a compelling scientific reason to conduct pharmacogenetic analysis during a clinical trial, it would not be pragmatic to include this element in the research.
3.11 It has been suggested by one commentator that by 2014 ‘all new medicines [will be] required to use SNP analyses for clinical trials and surveillance’.5 This projection is based on the presumed economic advantages to be gained by pharmacogenetic analysis in the development of new medicines. If, as this prediction suggests, panels of SNPs are developed and it becomes comparatively inexpensive to use such pharmacogenetic profiles in clinical trials, it is possible that there will be further regulatory and legal pressure on companies to pursue this approach. However, it is difficult to predict at this stage just how widespread the application of pharmacogenetics in research will become.
3.12 Pharmacogenetic analysis has the potential to improve our understanding of medicines and to produce safer and more effective medicines. We recommend that the appropriate use of pharmacogenetic analysis in clinical trials should be promoted. Regulators should be encouraged to promote the collection and storage of samples in clinical trials such that they could be subjected to pharmacogenetic analysis either during the trial, or subsequently. We consider questions of how best to obtain consent to the taking of such samples, and the manner in which data should be stored, in paragraphs 3.27 – 3.49.
Footnotes5 Roses AD (2001) 2025: the practice of neurology: back from the future, Arch Neurol 58: 1766-7.