1.  ABOUT ROCHE IN THE UK

  1.1  Roche has been committed to improving the health and well-being of people in the UK, from birth to old age, for more than 90 years. Our aim is to enhance the quality of life for everyone.

  1.2  Today, we are market leader in three of the four business areas in which we operate—pharmaceuticals, diagnostics, consumer health and vitamins. We are the second largest foreign investor in UK healthcare and plough back more than 20 per cent of our turnover into research and development, well above the industry average. By taking an integrated approach to healthcare, we can offer superior solutions that are tailored to the individual.

Diagnostics

  The development, production and marketing of innovative tests and systems to improve the detection, screening, evaluation and monitoring of disease.

Pharmaceuticals

  The discovery, development, production and marketing of clinically and cost-effective prescription drugs to combat human disease. Roche has significant research and products interests in obesity and weight management, oncology, diabetes, cardiovascular diseases, transplantation, renal medicine, virology and influenza, in particular.

Consumer health

  The development, production and marketing of some of the UK's best-known over-the-counter healthcare brands, including Sanatogen^®, Rennie^®, Redoxon^®, Aspro^®, Radian^®-B and Berocca^®.

Vitamins

  The development, manufacture and marketing of vitamins, carotenoids and various pre-mixes for animal and human nutrition, food production, healthcare and cosmetics industries.

  1.3  Roche first established a UK sales and marketing presence in 1908, with research and manufacturing activities starting 30 years later. Roche now employs almost 3,000 people in the UK at facilities in Welwyn Garden City, Witham, Lewes, Heanor, Dalry and Belfast.

2.  ROCHE GENETICS AND GENOMICS RESEARCH

  2.1  Genetics is the study of heredity: how biological information is transferred from one generation to the next as well as how that information is expressed within an organism.

  2.2  Genomics is the study of genes, and is commonly used to describe the process of locating, characterising and discovering the function of genes. A relatively new but rapidly expanding field of research, genomics can be applied to humans, animals, plants and bacteria.

  2.3  Genomics looks set to revolutionise human healthcare. Many common human diseases have been shown to have a genetic basis or component, which can affect disease onset or response to treatment. By understanding gene function, researchers can gain an in-depth and fundamental insight into human disease, and hence develop new or improved therapeutics and diagnostics.

  2.4  Roche has been strongly committed to research since its founding over 100 years ago. Today, genetic research is a major part of Roche's Research and Development programme as we believe it to be an essential and indispensable element in providing better health care, provided it is implemented based on scientific, ethical, social and legal principles.

  2.5  Roche is applying research in human genetics, genomics and proteomics to develop strategies and products for individualised healthcare delivery. The emphasis is on developing integrated solutions spanning the full range of medical services, from disease prevention and diagnosis to treatment. Roche is committed to pursuing this work in accordance with the standards set forth in the Roche Charter on Genetics (see Appendix 1 [not printed]).

3.  ROCHE'S SUBMISSION

3.1.  What current Roche projects involve collecting genetic information on people living in the UK?

  Roche is currently collecting DNA samples from consenting subjects within the UK, as part of the following clinical drug development trials worldwide:

(i)  NK1 receptor antagonist in the treatment of anxiety/depression;

(ii)  Trocade in the treatment of Rheumatoid Arthritis;

(iii)  Xeloda in the treatment of Colon Cancer.

  All such DNA samples will be held within an anonymised genetic databank, and thus such samples will not be associated with data as to country of collection.

3.2.  What other projects are about to start?

  Potentially anonymised DNA collection may be sought in planned trials of Xenical^® in the treatment of obesity but it is not yet certain if such trials will incorporate recruitment within the UK.

3.3.  Are there collections of material (eg tissue samples) in existence that could be used to generate databases of DNA profile?

  3.3.1  Yes. All DNA data-banking within the UK has been undertaken in accordance with Roche's own standards and policies governing the Roche Sample Repository and with ethical approval and subject consent. A copy of Roche's Patient Information Brochure relating to the collection and storage of samples is appended (Appendix 2 [not printed]).

  3.3.2  The resulting databank holds anonymised DNA samples with matching clinical data derived exclusively from Roche sponsored trials. Access to the Repository is strictly controlled and subsequent investigations are limited to the original therapeutic area of ascertainment. Clinical data will not be added prospectively or retrospectively from other sources.

3.4  Why are these genetic databases being assembled? To what purposes will they be put?

  In keeping with the Roche Charter on Genetics, Roche is committed to making maximal use of the evolving techniques of pharmacogenetics to help provide more effective and safer pharmaceuticals. The Roche Sample Repository represents a resource of anonymised DNA samples and accompanying medical data, aimed at meeting the clinical requirements of introducing exploratory genetic analysis into pharmaceutical research and development, whilst maintaining optimal subject privacy and procedural transparency.

3.5  How are these activities funded?

  Clinical genetic research is an integral part of Roche's commitment to generate meaningful improvements in patient care through scientific advances in therapeutics and diagnostics, and as such is funded exclusively by Roche, as part of its drug development strategy.

3.6  What practical considerations will constrains developments?

  The recent publication of a draft sequence for the human genome, and the imminent availability of a high-density genetic map from the publicly/privately funded SNP Consortium, suggests that technical requirements are unlikely to be limiting in the pursuit of pharmacogenetic medical advances in the near future. As such, primary constraints seem likely to stem from the operating environment dictated by regulatory requirements for registration of novel drugs and local legislation and guidance dictating optimal approaches to maintaining privacy for individual genetic data.

3.7  Are there alternative ways of fulfilling the same objectives, which do not involve the assembly of genetic databases?

  The major public health advances of the next two decades must inevitably come from improvements in the prevention and treatment of common disorders of middle to old-age. Such disorders include coronary heart disease, osteoporosis, obesity, type II diabetes mellitus and Alzheimer's disease. The cause of such diseases are complex and "polygenic" in nature, stemming from the interplay of several genetic determinants together with diverse environmental factors. Consequently, the genetic aetiology of such disease can only be understood through the study of population genetics. As such, there is no scientific alternative to collection of DNA samples from representatives of such populations. This reality is reflected in the large-scale efforts currently underway in both the public and private research sectors to build these kinds of genetic investigational resources.

3.8  What is the genetic information that is being collected?

  Genetic data stored within the Roche Sample Repository is solely related to the results of genotyping markers at and around candidate genes and loci believed directly relevant to study of the therapeutic area from which the samples were originally collected. That is to say, samples collected from subjects with diabetes will only be associated with genetic data aimed at increasing understanding of diabetes and related processes.

3.9  How is this genetic information being stored, protected and kept secure?

  At all times Roche serves as a responsible custodian of donated genetic material and data, assuming total responsibility for proper safekeeping and confidentiality of all samples and associated data. Operational structures and processes have been framed such as to ensure that only a strictly limited number of specifically authorised Roche personnel have access rights to both the clinical database and the Roche Sample Repository database. Operational procedure specifically forbids any "assumptive" re-identification of anonymised samples on the basis of unique clinical data. All such processes are subject to appropriate internal and external audits to monitor and ensure compliance.

3.10  What do you see as the Roche group's responsibility regarding:

Privacy

3.10.1  Roche respects the right of every individual to privacy and confidentiality regarding their genetic information. As such, in addition to recognising corporate and individual obligations to abide by national and international research standards and applicable laws, Roche also voluntarily assumes pre-eminent responsibility in preventing the misuse of genetic information obtained in the course of its research activities. Such misuse of genetic information has been deemed to include, but is not limited to, the support of discrimination against, or exploitation of, any individual or group of individuals. Roche recognises such responsibilities as a matter of policy.

  3.10.2  Further to such issues, Roche has decided to adopt an anonymised approach wherever possible for genotyping and banking of genetic data, which together with aggregate reporting thereby ensures maximal subject privacy. All samples entered into the Roche Sample Repository are assigned a new, independent code within the dedicated database system. Subsequent and obligatory deletion of the key linking clinical identifiers and encrypted Repository database identifiers, delivers effective "anonymisation".

  3.10.3  In order to prevent compromise of such anonymisation through reporting of "exceptional" genetic data, potentially capable of uniquely identifying a single individual participating in any genetic collection, any and all data collected within the Roche Sample Repository will only be analysed and reported in aggregate. The Repository will not serve to determine or interpret genetic information on an individual level.

Consent

  3.10.4  Roche respects and actively supports the right of every individual to absolute self-determination in the ascertainment and use of genetic information, with regard to both research and personal health care. Consequently, Roche works to provide a complete transparency of purpose in all dealings with subjects invited to participate in Roche Sample Repository research protocols. This transparency extends to the planned and potential uses of any donated DNA and derived genetic information for the discovery and delivery of new and improved diagnostics and therapeutics.

  3.10.5  Against this background of openness of purpose, all participation in the Roche Sample Repository is entirely voluntary in nature. Roche policy dictates and guarantees independence of individual choice as to participation in DNA collection for the Roche Sample Repository with respect to choice as to participation in any Roche sponsored clinical trial. Practicable control of collected samples, including the right to withdraw samples from the Repository at any time whilst participating in the associated clinical trial, remains with the participant. Subsequent anonymisation of the sample renders reliable identification for withdrawal impossible.

Future Use

  3.10.5A  Roche recognises the legitimate interest of society in applying the aggregate results of genetic studies to the improvement of the human condition. It perceives a universal recognition that identification of the best potential candidate genes for pharmacogenetic investigation is not always possible at this stage of our understanding of genetics.

  3.10.6  As such Roche appreciates the value of using genetic resources within the Roche Sample Repository for future as yet unforeseen investigation. This intent is made entirely transparent to participants prior to establishing their consent for DNA collection. In addition, the maximal time the sample will be retained to allow for such investigation is strictly prescribed by Roche Sample Repository policy at 15 years. All genetic investigational strategies, not made absolutely explicit at the time of collection and institutional ethical review, will only be undertaken in accordance with guidance and counsel actively sought from an independent scientific and ethics advisory group. This group consists of acknowledged experts, from outside of Roche, representing the fields of biology, ethics, sociology, law as well as the community.

Public Accountability

  3.10.7  Roche recognises a duty to integrate the principles enumerated above into a programme of scientifically and socially responsible, accountable, and transparent use of genetic information for the development of new diagnostics and therapeutics. As such, Roche is actively engaged in a programme of communication and education with all stakeholder communities, to build understanding of Roche's position in genetic research and promote ongoing debate as to best practice in maintaining optimal ethical and social accountability. In particular, Roche has adopted, and actively promotes to other participants in the field of pharmacogenetics, a rigorous policy ensuring the obligatory timely public communication of research results to the scientific community. Such open communication is a pre-requisite of accountability.

Intellectual Property Rights

  3.10.8  Roche's purpose in supporting pharmacogenetics, within the UK and elsewhere, is as an adjunct to their traditional drug development activities. It is thereby hoped to realise the promise of using genetic information for the discovery and development of new and improved diagnostics and therapeutics. Consequently, Roche has a requirement for adequate protection of its intellectual property, to allow subsequent investment in the delivery of such advances. Adequate protection of intellectual property is particularly important in the light of Roche's stance on timely public communication of the results of genetic analysis.

  3.10.9  In keeping with the transparency of the protocols underlying the Roche Sample Repository, the intent of Roche to acquire and maintain intellectual property rights pertaining to therapeutic and diagnostic advances is made explicit during the process of establishing subject consent for DNA collection, as is the intent of Roche to actively pursue therapeutic and diagnostic advances.

3.11  How do you see Roche's activities in the area of genetic databases developing in the future?

  Roche's commitment to pharmacogenetics, and vision of the resultant benefits of its application, is both strategic and long term. As such, future clinical development within Roche will include systematic and comprehensive assessment of the potential benefits of introducing genetic analyses. These analyses will be prioritised where it is believed they will provide greater aetiological understanding of disease or enhanced therapeutic efficiency/safety. Inevitably, this activity will translate into an increase in the level of DNA collection sought within the UK and elsewhere in the world, in association with traditional drug development trials.

3.12  What lessons, if any, should be learnt from genetic database initiatives in other countries?

  Roche's commitment to the use of genetic analysis is global in nature and scope. Inherent in such an approach, is the assumption that the very highest standards of ethical and scientific research will be universally adhered to and actively promoted.

  Retrospective analysis of the limited examples of successful prosecution of DNA data-banking in other countries would suggest such success to stem from:

—  Establishing a clear sense of scientific purpose.

—  Building effective methods for sample de-identification and protection of individual genetic privacy.

—  Ensuring transparency of policy and procedure.

  The progress of the DeCODE initiative in Iceland, in rapidly discovering novel candidate loci for such major public health problems as stroke and late onset Alzheimer's disease, has been widely reported. This would seem to entirely underscore the faith of Roche and other investigators in the ability of genomic and genetic analysis utilising human genetic databases to help provide more effective and safer pharmaceuticals in the near future.

John Melville
Managing Director

3 October 2000