Implications for clinical services in Britain and the United States
BMJ 1998; 316 doi: https://doi.org/10.1136/bmj.316.7133.767 (Published 07 March 1998) Cite this as: BMJ 1998;316:767
- Ann Louise Kinmonth (alk25{at}medschl.cam.ac.uk), professor of general practicea,
- John Reinhard, associate clinical professor of medicineb,
- Martin Bobrow, professor of medical geneticsc,
- Susan Pauker, assistant professord
- a General Practice and Primary Care Research Unit, Institute of Public Health, University of Cambridge, Cambridge CB2 2SR
- b State University of New York at Buffalo, Buffalo, NY, USA
- c University of Cambridge, Department of Medical Genetics, Addenbrooke's Hospital, Cambridge CB2 2QQ
- d Genetics Department, Harvard Pilgrim Health Care, Boston, MA 02116-3502, USA
- Correspondence to: Dr Kinmonth
This is the third of four articles discussing the broader implications of advances in genetics
Meeting the rising demand for genetic information and advice will require a major reorganisation of genetic services. In the United States, demand has led to the growth of private genetics services that are marketed directly to the public. In the United Kingdom, specialist genetic services are struggling to cope with increased workloads and it is acknowledged that some genetics services will have to be incorporated into mainstream clinical medicine, particularly at primary care level. A range of pilot schemes has been set up to establish how to do this, but few schemes have been fully evaluated. A broad educational effort is needed to increase awareness of the scope and potential of genetic information among health professionals and the public. This article reviews current developments and argues that contrasting approaches in Britain and the United States each offer special opportunities in innovation and evaluation.
Summary points
Advances in genetics underpin the need to equip primary care teams with skills to assess genetic risk of disease, discuss the implications of gene testing, and control access to specialist services
Involvement of primary care teams will vary with public awareness and uptake of tests, type and prevalence of disorder, precision of genetic tests, and therapeutic choices available
Despite increasing availability of genetic tests, it is premature to offer population screening for genetic predisposition (such as to breast cancer), and even the case for screening carriers for cystic fibrosis through primary care is uncertain
Different cultures of American and British health care may lead to faster innovation in United States but greater opportunity for development within a research framework in Britain
Current service configuration
The organisation of genetic services in the United Kingdom is currently based on regional centres. These mainly deal with relatively uncommon inherited and congenital disorders such as familial cancer and learning disorder syndromes. They provide information, advice, genetic testing, and counselling about opportunities for disease prevention to individuals and their families. Their ethos (stemming from historical ethical concerns about forced eugenics) has traditionally been based on non-directiveness and non-paternalism.1 Until recently clinical genetics was dominated by reproductive issues, but this may change rapidly as gene loci defining susceptibility to hereditary cancers (particularly breast cancer) and other common disorders are discovered.
In the United Kingdom the general practitioner's role in the diagnosis of genetic disorders has often involved indirect referral on clinical grounds. For example, cases of recurrent chest infection in infancy or recurrent miscarriage may be referred first to a local paediatrician or gynaecologist. Direct referral to geneticists arising from awareness of the implications of the family history are now increasing, and in the United States many patients refer themselves to geneticists.
Effects of rising awareness on workload of regional centres
In the United Kingdom there are currently only one or two consultant geneticists per million population. Increased interest and demand from patients and practitioners is already being felt, especially where regional centres are developing new services and raising awareness and expectations. Awareness is even greater in the United States, where websites and private genetics centres (box) promote genetic issues and testing opportunities.
Advances underpinning service developments
Scientific advances in genetics offer potential benefits to patients in three areas.
Better tests for uncommon conditions —There are increasingly precise predictive tests for those referred to the clinic with suspicion of carrying gene mutations for a range of simple inherited disorders such as β thalassaemia and cystic fibrosis.
New tests for rare cases of common conditions —Identification of previously unrecognised highly penetrant genetic susceptibilities, within broad clinical groups of common disease, have excited media, public and professional interest alike.2 The technical capacity to identify mutations at a particular gene locus allows, for the first time, the capacity to discriminate between the vast majority of people with small disease risks and small subsets at high risk which are otherwise clinically indistinguishable. Examples include breast cancer and early onset Alzheimer's disease.
New tests for common genetic contributions to common conditions—For common phenotypes with a contribution from low penetrance gene alleles, genetic advice can currently only be given in terms of empirical recurrence risks. In the next few years there is the possibility of tests developing that will identify specific risk predisposition or risk protection alleles for particular conditions and life styles and the search is on across the whole range of chronic diseases.3
If predispositional tests come to fulfil the classic criteria for screening,4 they could be applied to large populations of asymptomatic people.5 The rational introduction of any such tests for screening will critically depend on the availability of interventions of proved benefit among the population tested (or at least promising enough to justify further evaluation) and will for logistical reasons alone, be equally dependent on the involvement of primary care.5–7
These real and potential advances point to the need for primary care teams to develop the necessary skills to assess genetic risk, discuss the implications of gene testing, and hold the gate to specialist genetic services appropriately open or shut.
Genetics services on the world wide web
Genzyme Genetics (http://www.wwdir.com/genzyme.html)
Genetics & IVF Institute (http://www.givf.com/givfhome.html)
Public access to genetics services
In the United States genetic services are marketed directly to the public. Harvard Pilgrim Health Care, for example, provides a team of physicians and counsellors with expertise in genetics offering consultation, counselling, testing, support groups, education, and referrals. Through telephone access, the service is available 24 hours a day.
Guidelines for referral to consultation and counselling:
Concerned women considering pregnancy or already pregnant:
Age ≥35 years at delivery
Considering early prenatal testing
Have received an abnormal prenatal test result
Have an affected child
Had three or more miscarriages
Concerned couples having or already expecting a baby:
Genetically related
Known carriers of autosomal recessive disease
Have a known genetic condition
Family history of cancer; multiple cases, or multiple cancers
Exposure to chemicals/radiation
Education and support:
Updates in Medical Genetics on site at provider practices
On line computer database on genetics literature
“Difficult Decisions” monthly support group for patients
Educational materials and counselling
Referrals to other families in similar situations
Long term follow up and updating of risk assessment
Integrating genetic risk assessment into medical general practice
Many general practitioners do not yet feel much need to prepare for the kind of practice in which predispositional genetic testing for susceptibility to common disorders may become as routine as assessing biological or behavioural risk factors is now. Models for service development have thus primarily been set up by genetics centres alone or in collaboration with academic departments of general or family practice, or with health maintenance organisations (HMOs) or individual enthusiastic family doctors. Most have focused on testing for well understood conditions such as cystic fibrosis.
Genetics centres in the United States now offer comprehensive genetic care plans for large HMOs,8 or to other providers and their patients. Specialist clinics have been set up primarily to facilitate further clinical and basic research. In the United Kingdom, over the past decade a range of regional and national genetic registers have been established.9–12 Some, such as the familial adenomatous polyposi coli register in Newcastle, are linked to clinical care, with aims such as exclusion of people not at risk and reduction in early mortality among previously unrecognised gene carriers.9 Genetic registers (box) allow long term direct contact with families for continuing support and allow risk status to be updated and treatment options changed as they arise. The cost of verifying and maintaining these registers and linking them to primary care should not, however, be underestimated.10
A complex process
Genetic risk assessment is complex for needs (and demand) will vary over time, according to public and professional awareness, uptake of tests, the type and prevalence of the disorder for which tests are available, the precision of the tests, and the therapeutic choices available. 6 13–16
Cystic fibrosis is probably the most common autosomal recessive condition in the United Kingdom, and a range of pilot studies of genetic testing in general practice and commentaries on them have been published.17–24 Despite this the case for screening for carriers through primary care is still not fully made. Acceptability of the test offered through general practice is variable and depends heavily on the setting. Understanding of the test result varies, as do the choices of patients with positive results. Cost effectiveness has not been established, and resource needs, especially for post-test counselling, may be underestimated.
Tests that identify specific alleles predisposing to or protecting from particular conditions are under development; these could be applied to large populations of asymptomatic people
Predispositional testing poses further difficulties. Families need information before and after testing and support in understanding their newly defined status and its implications for marital, reproductive, and other life choices, as well as the implications for surveillance and early diagnosis or treatment. 2 24 25 The time and genetic expertise required may be substantial and it is unclear how it can best be shared between primary and secondary care.
Developing expertise in primary care
Potential testing strategies for rare familial cases of common conditions depend crucially on classifying individuals accurately into low, medium, and high risk groups, using information from the family history.6 The development of genetic expertise in primary care is likely to depend on establishing regional or locality based multiprofessional teams including genetic facilitators, counsellors, or nurse specialists who can provide accurate information and advice to local practices and their patients and liaise with voluntary groups and community leaders and genetic centres. Practice nurses will then be supported by nurse specialists or non-medically qualified counsellors linked with the multiprofessional team. Genetic assessment might be integrated into existing shared care schemes for diseases such as. haemoglobinopathies, diabetes, or asthma or into outreach services from clinical genetics centres directly.
Obtaining good family history data is an essential start in the assessment and management of genetic disorders, and the reliability of family histories obtained in primary care by direct questionnaire with or without computer or primary care practitioner support is being investigated by the NHS Research and Development and the Cancer Research Council's research programmes. Pedigree drawing programmes are available on the internet.26
Setting up a genetic register
Clear aims (research, clinical)
Sufficient resources for set up and maintenance
Defined access, ownership, and data confidentiality
Ascertainment of probands
Construction of pedigrees
Identification of family members at risk
Screening of members at risk
The epidemiological basis of guidelines for risk stratification on the basis of degree and number of relations and age at onset of disease requires strengthening. However, primary care guidelines clarifying the current limitations of genetic tests, and when referral for specialist advice may have no advantage, are becoming available.27 A study of intensive pretest counselling about BRCA1 gene testing among American women whose family history suggested they were at low to moderate risk showed that although the counselling increased their knowledge about the limitations of testing it had no effect on their desire to undergo testing.28 If such results are replicated in Britain, primary care practitioners may find it hard to be effective gatekeepers, even if they are armed with time and appropriate expertise.
Promoting professional and public awareness
Educated patients consulting educated practitioners must be the aim, and public understanding is being addressed through awareness initiatives such as the Gene Shop at Manchester Airport,29 consensus conferences, citizens' juries, and initiatives by organisations such as, in Britain, the Genetic Interest Group, which represents and supports charities, voluntary agencies, and support groups for those affected by or at risk of genetic disorders. Initiatives in undergraduate medical education are also under way.30 General practitioners' knowledge and expertise can be increased through contacts with specialist centres, special interest groups, involvement in development and use of guidelines, and by collaboration in research projects as well as through the traditional forms of continuing education.
Establishing the cost effectiveness of different models and educational approaches will be difficult, for the potential benefits and harms are numerous, hard to predict, and extend beyond patients to their families and future generations. 2 13 The costs of genetic screening thus relate as much or more to actions after testing than to the actual testing process.25 Some costs may be offset by reduced surveillance of people at low risk or with negative test results. For example, predictive tests given to women with more than four first degree relatives with breast cancer might be paid for from savings made by limiting mammography among young women, in whom cost effectiveness has not been proved.
Incorporating change
In Britain, pilot developments led by enthusiasts provide a constructive way of introducing and testing out new service developments.31 Pilot schemes in all sectors of health care are needed to define future service needs and professional roles. These schemes should incorporate risk management and appropriate referral and advice to the many relatives who have concerns but often have no additional genetic risk. Such an approach provides balance to the pressure to incorporate new technology into practice before it is fully evaluated. It also allows for the realities of the unpredictable development of knowledge and the need to gain experience of service applications while accumulating evidence of their cost effectiveness. Introducing services within a research and development framework allows for defining the general principles underpinning care, spanning the processes and clinical outcomes of different configurations of service delivery, and evaluating psychological and social impacts on individuals and families. 25 32 Comparison across tests and disorders is likely to provide valuable generic information. 33 34
In the United States, most health care is provided through insurance and health maintenance organisations. Consumer demand and fear of litigation more readily drive healthcare activity than in Britain. Managed care maximises the ability to take advantage of unique local conditions and develop a flexible approach to programme development. Clinical and financial accountability, integrated healthcare systems, responsiveness to consumer concerns, and the ready availability of advanced computer systems to collect clinical and financial data are other advantages.
Conclusion
Clinical geneticists and innovative primary care teams on both sides of the Atlantic have a key role in planning, developing, implementing, managing, and evaluating services for the assessment and management of genetic risk. They also have a crucial part to play in devising training and support for clinical colleagues and ensuring that pilot programmes are evaluated rigorously. Genetic testing, wherever it is carried out, must be based on an accurate understanding of the clinical course of disease, the views of the patients (and their relatives), the performance of the tests, and the effectiveness of treatments or preventive strategies.
Acknowledgments
We thank the many colleagues in clinical and public health medicine who commented so constructively on earlier drafts, and Fawzia Khan and Fiona Walker for literature searching.
Funding: No additional funding.
Conflict of interest: None.