INTRODUCTION

  Pfizer has been requested to provide information for the House of Lords inquiry into Human Genetic Databases. The questions posed and the specific answers are detailed below. Pfizer is committed to the discovery and development of medicines that can contribute significantly to the treatment of disease and quality of life. As part of this commitment we use the best scientific evidence and technologies available to improve our ability to deliver new medicines. The revolution in genetics and genomics that has delivered the draft sequence of the human genome during 2000 is giving rise to improved opportunities to diagnose disease and identify predictors of response to medicine at the individual level. We believe that it is imperative to make use of this information to improve our ability to develop medicines. As a result, Pfizer Global Research and Development is pursuing the collection and databasing of genetic information that can contribute to our research efforts, but we recognise the sensitivity with which genetic information is viewed. Thus in order to support our research we have invested heavily in the technology that will allow us to conduct the research whilst affording the greatest possible protection to individuals who donate samples.

1.  What current projects involve collecting genetic information on people in the UK? What other projects are about to start? Are there collections of material (eg tissue samples) that could be used to generate databases of DNA profiles?

  Currently, Pfizer Global Research and Development collects samples from subjects participating in clinical trials for the purpose of genetic analysis using two different approaches:

(a)  Collection of samples for non-anonymised analysis. The first approach is to collect samples which will be analysed for specific genetic variants that are appropriate to study for the disease, or drug, being evaluated. An example would be the analysis of variants in drug metabolising enzyme genes. This genetic analysis can help to explain the variation in drug levels among individuals when the results of the clinical trial are analysed. These samples are collected and labelled in the same way as samples which are collected for the analysis of biochemical parameters. The samples are destroyed after the studies have completed;

(b)  Collection of samples for anonymised analysis. The second approach is to collect samples for future DNA analysis for genes not currently identified. In this approach a broader consent is requested from the subject. This sample is treated differently—it is anonymised and linked to the anonymised clinical data from that patient using a specially designed and secure anonymisation process. Subject to Ethics Committee approval and patient informed consent we aim to collect samples for anonymised genetic analysis from all subjects participating in phase II and phase III clinical trials conducted by Pfizer Global Research and Development. These collections of samples are used only for clinical research purposes and cannot be used to generate databases of DNA profiles.

2.  Why are these genetic databases being assembled? How are these activities funded? What practical considerations will constrain developments? Are there alternative ways of fulfilling the objectives?

  These genetic databases are being assembled primarily to allow us to examine the genetics of drug response. In future, when all genes and the variants of genes are known, we will be able to examine those specific genetic factors which contribute to the efficacy and safety of the compounds we develop. A secondary use of these data will be to explore the association between genetic variation and disease which will help us better understand the diseases we are targeting our compounds at. These activities are funded from the research budget of Pfizer Global Research and Development. Practical considerations that constrain the development of these databases at the level of collection concern ethics committee approval and subject informed consent. The key to understanding and evaluating the genetics of drug response lies in the access to the data collected during our clinical trials. These data together with stored samples provide the only mechanism to support analyses of genetic variability in drug response. Examination of the genetics of disease could be examined through collaboration with other companies or academic institutions which have appropriate collections of samples and clinical data. This is done on a specific collaboration by collaboration basis.

3.  What is the genetic information that is being collected? How is it being stored and protected?

  The genetic data derived from non-anonymised samples are given the same degree of protection afforded to clinical and biochemical data collected from an individual subject during a clinical trial. The standard operating procedures (SOPs) applied to clinical trials data apply with equal force to any genetic data derived as part of a clinical trial.

  The genetic data derived from anonymised samples are given additional protection. For the anonymised samples, genetic analyses cannot be performed on the samples until the link to personal identifying data has been permanently deleted. The data derived from these samples are linked with anonymised clinical data and kept in a separate database with strict controls over access.

4.  How do the organisations involved see their responsibilities regarding privacy; consent; future use; public accountability; and intellectual property rights?

  We take our responsibilities with regard to consent and privacy very seriously. We recognise the sensitive nature of genetic information and have designed our anonymisation process to provide maximum protection to individual sample donors. Before any sample is taken for any genetic analysis (anonymised or otherwise) we seek approval from an Independent Ethics Committee. Subject to this approval, informed consent is then obtained from each participating individual. Our anonymisation and security procedures have been developed in order to ensure that no-one in the future will be able to make the link between an anonymised sample and the individual who donated it. We abide by the regulations and ethical imperatives applied to clinical trials and incorporate these principles into our genetic analyses. We routinely protect our ideas and investment, and the genetics area is no different from any other. Thus the intellectual property associated with the samples and data is derived from the analysis and resides with the company.

5.  How do they see their activities in the area of genetic databases developing in the future? What advances in sequencing, screening and database technology are they anticipating?

  We see the value of genetic databases in improving our ability to design and develop better drugs for patients. The development of genetic databases is designed to support this by improving our understanding of diseases and individual responses to treatment. Advances in high-throughput genotyping will reduce cost and improve efficiency such that genome-wide screening of individuals using variants called SNPs will become a reality, improving dramatically our ability to predict the contribution of genetic variation to disease and drug response. These advances will make the development of genetic diagnostics for drug response a reality over the next 10 years. Advances in database development will make it possible to handle enormous quantities of data making complex data analysis practicable.

6.  What lessons should be learnt from genetic database initiatives in other countries?

  There is considerable variation in attitudes and understanding about the value and use of genetic databases from country to country. Concerns and protection for the individual are the paramount issues although the approaches to solving these problems are different. Developments in other countries highlight the need to ensure that informed public debate takes place. In addition, regulatory, legal and ethical positions vary from country to country. A standard position adopted and agreed by many countries would considerably improve the ability to conduct this kind of research.

CONCLUSION

  Pfizer Global Research and Development is pursuing the collection of samples and the development of genetic databases which will allow us to examine the relationship of genetic variation to drug response and disease aetiology. Specific technologies and procedures have been developed to protect individual subject confidentiality in addition to that normally accorded to subjects who participate in clinical trials. We believe that the sensitive and appropriate use of genetic information will lead to significant improvements in the development of drugs in the future.

October 2000