Implementing risk-stratified screening for common cancers: a review of potential ethical, legal and social issues.

BACKGROUND: The identification of common genetic variants associated with common cancers including breast, prostate and ovarian cancers would allow population stratification by genotype to effectively target screening and treatment. As scientific, clinical and economic evidence mounts there will be increasing pressure for risk-stratified screening programmes to be implemented. METHODS: This paper reviews some of the main ethical, legal and social issues (ELSI) raised by the introduction of genotyping into risk-stratified screening programmes, in terms of Beauchamp and Childress's four principles of biomedical ethics--respect for autonomy, non-maleficence, beneficence and justice. Two alternative approaches to data collection, storage, communication and consent are used to exemplify the ELSI issues that are likely to be raised. RESULTS: Ultimately, the provision of risk-stratified screening using genotyping raises fundamental questions about respective roles of individuals, healthcare providers and the state in organizing or mandating such programmes, and the principles, which underpin their provision, particularly the requirement for distributive justice. CONCLUSIONS: The scope and breadth of these issues suggest that ELSI relating to risk-stratified screening will become increasingly important for policy-makers, healthcare professionals and a wide diversity of stakeholders.

Public health genomics and personalized prevention: lessons from the COGS project.

Using the principles of public health genomics, we examined the opportunities and challenges of implementing personalized prevention programmes for cancer at the population level. Our model-based estimates indicate that polygenic risk stratification can potentially improve the effectiveness and cost-effectiveness of screening programmes. However, compared with 'one-size-fits-all' screening programmes, personalized screening adds further layers of complexity to the organization of screening services and raises ethical, legal and social challenges. Before polygenic inheritance is translated into population screening strategy, evidence from empirical research and engagement with and education of the public and the health professionals are needed.

Stratified cancer screening: the practicalities of implementation.

BACKGROUND: Improving understanding of the genetic basis of disease susceptibility enables us to estimate individuals' risk of developing cancer and offer them disease prevention, including screening, stratified to reflect that risk. Little attention has so far been given to the implementation of stratified screening. This article reviews the issues that would arise in delivering such tailored approaches to prevention in practice. RESULTS: Issues analysed include the organisational context within which implementation of stratified prevention would occur, how the offer of screening would be made, making sure consent is adequately informed, how individuals' risk would be assessed, the age at which risk estimation should occur, and the potential use of genetic data for other purposes. The review also considers how management might differ depending on individuals' risk, how their results would be communicated and their follow-up arranged, and the different issues raised by modification of an existing screening programme, such as that for breast cancer, and the establishment of a new one, for example for prostate cancer. CONCLUSION: Stratified screening based on genetic testing is a radically new approach to prevention. Various organisational issues would need to be considered before it could be introduced, and a number of questions require further research.

Risk prediction models: a framework for assessment.

BACKGROUND: Medical risk prediction models estimate the likelihood of future health-related events. Many make use of information derived from analysis of the genome. Models predict health outcomes such as cardiovascular disease, stroke and cancer, and for some conditions several models exist. Although risk models can help decision-making in clinical medicine and public health, they can also be harmful, for example, by misdirecting clinical effort away from those who are most likely to benefit towards people with less need, thus exacerbating health inequalities. DISCUSSION: Risk prediction models need careful assessment before implementation, but the current approach to their development, evaluation and implementation is inappropriate. As a result, some models are pressed into use before it is clear whether they are suitable, while in other cases there is confusion about which model to use. This paper proposes an approach to the appraisal of risk-scoring models, based on a conference of UK experts. SUMMARY: By specifying what needs to be known before a model can be judged suitable for translation from research into practice, we can ensure that useful models are taken up promptly, that less well-proven ones undergo further evaluation and that resources are not wasted on ineffective ones.

Polygenic susceptibility to prostate and breast cancer: implications for personalised screening.

BACKGROUND: We modelled the efficiency of a personalised approach to screening for prostate and breast cancer based on age and polygenic risk-profile compared with the standard approach based on age alone. METHODS: We compared the number of cases potentially detectable by screening in a population undergoing personalised screening with a population undergoing screening based on age alone. Polygenic disease risk was assumed to have a log-normal relative risk distribution predicted for the currently known prostate or breast cancer susceptibility variants (N=31 and N=18, respectively). RESULTS: Compared with screening men based on age alone (aged 55-79: 10-year absolute risk ≥2%), personalised screening of men age 45-79 at the same risk threshold would result in 16% fewer men being eligible for screening at a cost of 3% fewer screen-detectable cases, but with added benefit of detecting additional cases in younger men at high risk. Similarly, compared with screening women based on age alone (aged 47-79: 10-year absolute risk ≥2.5%), personalised screening of women age 35-79 at the same risk threshold would result in 24% fewer women being eligible for screening at a cost of 14% fewer screen-detectable cases. CONCLUSION: Personalised screening approach could improve the efficiency of screening programmes. This has potential implications on informing public health policy on cancer screening.

Predicting the risk of coronary heart disease. II: the role of novel molecular biomarkers and genetics in estimating risk, and the future of risk prediction.

This is the second of two articles reviewing recent findings about the risk of coronary heart disease. This paper is concerned with novel molecular biomarkers, genetic markers of risk and the future of risk prediction.

Predicting the risk of coronary heart disease I. The use of conventional risk markers.

This is the first of two articles reviewing recent findings about the risk of coronary heart disease. This paper is concerned with conventional risk factors; the second will review novel molecular biomarkers, genetic markers of risk and the future of risk prediction. Predicting exactly the future occurrence of coronary heart disease (CHD) is not possible, but the risk can be estimated with models based on cohort studies. Most existing models are based on long-standing research on the residents of Framingham, Massachusetts. The findings from Framingham yield inaccurate results when applied to contemporary populations elsewhere. In particular, they may exacerbate health inequalities. This is because the incidence of and mortality from CHD have fallen recently, the Framingham cohort differs from many groups to which findings from it have been applied, important risk factors such as ethnicity, socio-economic deprivation and family history are absent from the Framingham equations and susceptibility to risk factors varies between populations. Attempts to recalibrate or adjust the Framingham equations to improve their performance have not been shown to overcome these problems. SCORE, QRISK, PROCAM and ASSIGN are risk prediction models that have been developed based on different cohorts. The group developing NICE's guideline on lipid modification was uncertain about which risk prediction model to recommend for use in the NHS. Eventually they selected a modified version of the Framingham equation. However, QRISK appears to offer the best long-term promise.

Integrating educational objectives and the evaluation process in a general surgery residency program.

Although the Accreditation Council for Graduate Medical Education (ACGME) requires that all of its approved residency programs have written goals and objectives and an evaluation process, many programs have difficulty achieving these goals. For eight years, the general surgery residency program at Abington Memorial Hospital has used a system that integrates each rotation's cognitive, clinical, and procedural objectives into the faculty's evaluation of residents and residents' evaluation of the rotation. The integration of goals and objectives with the post-rotation evaluations provides the program with an ongoing and continual assessment of each resident's progress, the effectiveness of the faculty as teachers, and the educational value of each rotation. In this essay, the authors describe this integrated system and provide examples of one rotation's goals and objectives and the evaluation forms used by faculty and residents.

The MODEL project: a scoring system to manage demand for cataract and joint replacement surgery.

Cataract surgery and joint replacement are highly cost-effective procedures; however, their availability is inequitable and doctors lack guidance on whom to refer and treat. We investigated the feasibility of using a scoring system to assess patients' suitability for operation. Wefound acceptable correlations between the scores ofgeneral practitioners and surgeons for both procedures. Scoring systems can be used in a consistent way bygeneralpractitioners and surgeons, and can make a contribution towards matching patients' needs with available treatment capacity.

Recent changes in the workload and clinical experience of pre-registration house officers: experiences over four years in south-west England.

We aimed to measure changes in the training and workload of pre-registration house officers using a postal questionnaire. Two hundred and six pre-registration house officers in the south-western region of England were surveyed and asked to report on the education, training and workload of their posts. Results were compared with a survey conducted four years earlier. Since the previous survey, the number of hours on duty had reduced from a median of 80 h week-1 in 1992/3 to 72 h week-1 in 1996/7 (P < 0.0001). There were no statistically significant changes in the number of patients admitted or clerked in an average week, but house officers' clinical experience had fallen. All but five of 26 marker conditions showed a decline, which was statistically significant in seven cases. House officers were keener to include four months of general practice in the pre-registration year and were less adverse to extending the pre-registration year to two years. The reduction in hours of work for house officers has been accompanied by a decline in their clinical exposure to common medical and surgical emergencies. The long-term effects of these changes are unknown.

Adult sacrococcygeal teratomas.

We report a rare case of a benign adult sacrococcygeal teratoma discovered during pregnancy. The cystic mass was confirmed on CT scan and magnetic resonance imaging. In the fifth postpartum month, three cysts (1, 2.5, and 6 cm) were excised. Pathologically, the specimens contained differentiated tissue from all three germ layers, including endocrine tissue within the ectopic exocrine pancreas.

Maximizing the contribution doctors make to NHS management.

Management is an increasingly important issue for many doctors. If doctors wish to influence resource allocation, they must involve themselves in health service management. This article describes the results of an enquiry action learning project involving six doctors. As part of the project, clinical directors and their business managers were interviewed. In addition, the Police Force and BAA (formerly the British Airport Authority) were visited and their management structure, out-of-hours activities and planning for emergencies assessed. This article examines the reasons why many doctors do not involve themselves in management, such as increased time commitment and negative peer pressure, and suggests some solutions to these problems, including the need for a wider understanding of the role of clinical directors. It also considers how some organizations are already starting to address these issues, and how both doctors and hospitals can benefit from greater involvement of doctors in health service management.

Part III. Performance measurements of primary care physicians in managed care.

A fundamental change occurring for physicians is that there are increasingly organized efforts to comprehensively assess physician performance. Managed care is the factor most instrumental in leading to an enhanced focus on physician measurements. Another major factor that has prompted increased attention to the measurement of physicians' performance is that patients are beginning to act more as consumers of health care. Efforts to measure physician performance in geographically dispersed primary care practices is inherently more difficult than measuring hospital care. However, according to some studies that have attempted to do this, the delivery in primary care offices of basic preventive services and the care given to patients with chronic illnesses is surprisingly poor. If primary care physicians don't address these issues, managed care companies will make it policy to refer some patients with chronic disease to specialists, who are comprehensively achieving higher measurement scores. What is being measured is at present quite variable in different primary care offices. Most of the initial measurements have been from claims data or from other data that might be obtained and aggregated outside of the primary care physician's office. As this data is not very rich in clinical information, significant misinterpretation is possible. In order to augment these shortcomings, office records are increasingly being reviewed. A standardization of primary care physicians' office medical records is rapidly occurring and is being driven by the measurable items reviewed by managed care organizations. Measurement of patient complaints and patient surveys is another means that managed care organizations presently use to assess primary care physicians' performance. Extreme caution should be used when interpreting this data, as often the small numbers of patients, multifactorial issues, and ambiguity about responsible parties may skew the results. Measurement processes are evolving to focus on how the health care system functions in an integrated fashion, instead of strictly on how the individual physician is performing. Present and planned measurement processes should be used to improve care of patients, and this is most likely to occur when physicians take an active role in understanding and responding to the measurement processes arising from managed care.

Training and privileging for new procedures.

Hands-on training for advanced laparoscopic procedures is more difficult to obtain than for basic laparoscopy, but because morbidity and mortality rates for these technically demanding procedures are higher, adequate training is essential and obtained, ideally, through a formal fellowship in advanced laparoscopy. Shorter preceptorships can provide adequate training but are more difficult to find. Few advanced laparoscopic procedures are experimental, but the safety of each must be ensured before a hospital awards privileges for their performance. Vigilance regarding local and national outcomes of these new procedures is essential in this rapidly evolving field.

Accuracy of serology for the diagnosis of Helicobacter pylori infection--a comparison of eight kits.

AIMS: To determine the accuracy of eight commercially available kits for the serological diagnosis of Helicobacter pylori infection, and hence whether a serology service could be introduced to reduce endoscopy workload. METHODS: Eighty four patients newly presenting to their general practitioners with dyspepsia were recruited. Gold standard diagnosis of H pylori infection was obtained both by a histological examination of gastroduodenal biopsy specimens and by the 14C-urea breath test (UBT). The performance of six quantitative and two qualitative enzyme linked immunosorbent assays for H pylori IgG, used according to the manufacturers' instructions, with serum samples obtained during the endoscopy visit, were compared. RESULTS: The study population had a median age of 45 years, and the prevalence of H pylori infection was 35%. With one exception, where the patient had received a course of anti-H pylori treatment between endoscopy and UBT, there was 100% concordance in the results of the two gold standard techniques. Discordant serology results were more common in patients aged > 50 years (42% of the total) than in younger patients (21%), and this was most noticeable in uninfected patients. The sensitivity of the kits was good (90-100%), but specificity was more variable (76-96%), and the rate of equivocal results was unacceptably high in some cases (0-12%). The overall accuracy of the kits ranged from 83 to 98%. Two kits in particular performed well (Pylori-Elisa II, Bio-Whitaker and Premier, Launch; qualitative) with 98% and 100% accuracy, respectively. CONCLUSIONS: In a symptomatic population with a prevalence of H pylori infection of 35%, particularly in patients aged < 50 years, some but not all serology kits may be used as a highly accurate and inexpensive alternative to the gold standard techniques.