Adult Polycystic Kidney Disease and Insurance

Abstract

Adult Polycystic Kidney Disease (APKD) is a single-gene autosomal dominant genetic disorder leading to end-stage renal disease (ESRD, meaning kidney failure). It is associated with mutations in either of two genes, APKD1 and APKD2, and although diagnosis is still mostly by ultrasonography rather than DNA-based tests, this may change in the future. Recent studies have shown that the rates of onset of ESRD associated with APKD1 mutations are much greater than those associated with APKD2 mutations, a form of genetic heterogeneity that differs from, for example, familial breast cancer. In this paper we model the the impact of mutations in APKD1 or APKD2 on critical illness insurance, extending the work of Gutiérrez and Macdonald (2003), which was based on studies predating DNA-based tests. We then extend the model to life insurance and show that the financial impact is strongly dependent on the availability of treatment (dialysis and transplant), but that if it is available, extra premiums for life insurance are modest. We show that genetic heterogeneity introduces a novel problem, because carrying an APKD2 mutation is less risky than having a family history of APKD. Thus, in jurisdictions where family history may be used in underwriting but genetic tests may not, it may be illegal to use knowledge that benefits the applicant.     

Genetic developments in breast cancer

In this paper I have reviewed the current literature on the genetic mutations found in association with breast cancer. More emphasis has been given to BRCA1 because of the excitement generated with the cloning of this breast cancer susceptibility gene. A number of somatic mutations have been described (loss of heterozygosity, overexpression, and other mutations) in breast cancers. While strides have been made in unraveling the genetic basis of hereditary breast cancer (10 to 15 percent of all breast cancers), the genetic causes of most sporadic breast cancer (which comprise 85 to 90 percent) have yet to be discovered but they are likely the result of a step wise progression of cumulative genetic events, similar to those seen in colon cancer.     

Adult Polycystic Kidney Disease and Critical Illness Insurance

Abstract

Adult polycystic kidney disease (APKD) is a single-gene autosomal dominant genetic disorder leading to end-stage renal disease (ESRD, meaning kidney failure). It is associated with mutations in at least two genes, APKD1 and APKD2, but diagnosis is mostly by ultrasonography. We propose a model for critical illness (CI) insurance and estimate rates of onset of ESRD from APKD using two studies. Other events leading to claims under CI policies are included in the model, which we use to study (a) extra premiums under CI policies if the presence of an APKD mutation is known, and (b) the possible costs arising from adverse selection if this information is unavailable to insurers. The extra premiums are typically very high, but because APKD is rare, the possible cost of adverse selection is low. However, APKD is just one of a significant number of single-gene disorders, and this benign conclusion cannot be assumed to apply to all genetic disorders taken together. Moreover, ignoring known genetic risks in underwriting sets a precedent that could have unintended consequences for the underwriting of nongenetic risks of similar magnitude.     

Underwriting lethal genetic diseases

There are thousands of single gene deposits that cause increased morbidity or mortality risks. Few have complete penetrance leading to certain death. Most can be underwritten with affordable increases in premium; many at standard rates. As we learn more about penetrance for specific mutations we can learn to be more aggressive in underwriting inherited risks. I have described approaches to underwriting untested applicants to Huntington disease, and tested applicants who carry dominant mutations leading to breast, ovarian and colon cancer.     

Healthcare professionals’ perceptions of risk in the context of genetic testing for the prediction of chronic disease: a qualitative metasynthesis

Advances in genomic technologies and a growing trend towards stratified and preventive approaches to medicine mean that increasing numbers of individuals may have access to information about their genetic makeup, and their risk of developing diseases. This is likely to impact on healthcare professionals involved in the delivery of genetic tests, or in supporting patients who are affected by a disease with a genetic risk factor. It is therefore important to understand healthcare professionals’ perceptions about providing these services, and how they feel about communicating information about genetic risk to patients. This paper provides a systematic review and metasynthesis of qualitative research exploring healthcare professionals’ perceptions of genetic risk in the context of predictive genetic testing for chronic disease. Healthcare professionals expressed a range of reservations about the utility of predictive testing in this context. Professionals judged patients’ understanding of risk information to be limited and subject to bias and a range of sociocultural influences. Concerns about the psychosocial impact of genetic risk information were frequently cited, both in relation to individual patients and the wider impact on their families and communities. The need for provision of multidisciplinary support was described. The concept of responsibility was also an important theme. Healthcare professionals recognized the responsibility that accompanies risk knowledge, and that ultimately this responsibility lies with the patient, not the provider. Our analysis suggests that professionals’ evaluation of the utility of predictive genetic testing is influenced not only by resource deficits, but may also be interpreted as a response to challenging ethical and social issues associated with genetic risk, that are not well aligned with current medical practice.     

Gene-environment interactions and the complexity of human genetic diseases

In the assessment of mortality and morbidity risk, the ability of family history and genetic test results to predict the age of occurrence, severity, and long-term prognosis of 'genetic' diseases is important. An increasing number of gene-gene and gene-environment interactions have been demonstrated in a number of monogenic Mendelian diseases. These interactions can significantly modify the clinical presentation (disease phenotype) of diseases previously regarded purely as 'genetic.' As a result, 'genetic' diseases can be positioned in a continuum between classic Mendelian and complex disease where the extremes, pure genetic or solely non-genetic, do not exist. The position of any given disease in this continuum is defined by three components: the major gene(s) contributing to the phenotype, the variability added by modifier genes and the significance of environmental factors influencing the phenotype. As the predictive value of genetic test results can be significantly influenced by additional genetic and environmental risk factors, a better understanding of these factors may influence the quantification of mortality and morbidity risk.     

Huntington's disease,critical illness insurance and life insurance

We describe briefly a model of Huntington's disease (HD), a highly penetrant, dominantly inherited, fatal neurological disorder. Although it is a single-gene disorder, mutations are variable in their effects, depending on the number of times that the CAG trinucleotide is repeated in a certain region of the HD gene. The model covers: (a) rates of onset, depending on CAG repeat length as well as age; (b) post-onset rates of mortality; and (c) the distribution of CAG repeat lengths in the population. Using these, we study the critical illness and life insurance markets. We calculate premiums based on genetic test results that disclose the CAG repeat length, or more simply on a family history of HD. These vary widely with age and policy term; some are exceptionally high, but in a large number of cases cover could be offered within normal underwriting limits. We then consider the possible costs of adverse selection, in terms of increased premiums, under various possible moratoria on the use of genetic information, including family history. These are uniformly very small, because of the rarity of HD, but do show that the costs would be much larger in relative terms if family history could not be used in underwriting. We point out some difficulties involved in applying a moratorium that recognises simply a dichotomy between ‘carriers’ and ‘non-carriers’ of any mutation in a gene when these mutations are, in fact, very variable in their effects. These complexities suggest that restrictions on the disclosure, rather than on the use, of genetic information, if it became established as a principle, could deprive insurers of information needed for risk management even if not used in underwriting.     

Ethical Issues Resulting from Genetic Technology

Genetic tests are laboratory procedures that identify changes in our genes. Most human disease results, in whole or in part, from alterations in genes. Because the tests are expected to have incredible predictive power and because they may tell us personal information before we are ready to receive it, testing requested by a third party could be considered an infringement on privacy. Furthermore, the technology is new and thus subject to errors in interpretation that could result in unfair discrimination against the person who has been tested. Genes are inherited and are found not only in a single individual but also in some blood relatives. A genetic test therefore involves many people and invades the privacy of all. This paper questions the right of insurers to demand genetic tests but notes that by concealing the results of tests, applicants may practice adverse selection. If ethics are rules of conduct that society requires, then insurers will need to reexamine their ethical responsibilities in the light of this new technology.     

The Current State of Genetic Testing

Recent advances in genetic technology and progress in the multinational Human Genome Project are providing scientists with the ability to look into and manipulate the very makeup of life: the DNA molecule. We can already examine many dozens of plant and animal genes for disease producing abnormalities. In the near future, we will have the ability to alter specific genes in living tissue. This genetic technology holds great promise in our quest for preventing, diagnosing, treating, and predicting disease, not just in humans, but in all forms of life.

But there are some problems. Philosophically many are not ready for the implications of this technology. There are social and ethical issues that have not been well addressed, and which have, in part, resulted in an unprecedented amount of legislative activity over the past four years aimed at restricting access to and use of genetic information. The ability of the U.S. insurance industry to risk-select may be severely hampered if these restrictions are widely applied.     

Nonalcoholic fatty liver disease (NAFLD): a comprehensive review

Nonalcoholic fatty liver disease (NAFLD) is defined as fatty infiltration of the liver exceeding 5% to 10% by weight. It is a spectrum of disorders ranging from simple fatty liver (steatosis without liver injury), nonalcoholic steatohepatitis (steatosis with inflammation), and fibrosis/cirrhosis that resembles alcohol-induced liver disease but which develops in individuals who are not heavy drinkers. NAFLD is likely the most common cause of chronic liver disease in many countries. NAFLD may also potentiate liver damage induced by other agents, such as alcohol, industrial toxins and hepatatrophic viruses. The lack of specific and sensitive noninvasive tests for NAFLD limits reliable detection of the disease. It is often diagnosed on a presumptive basis when liver enzyme elevations are noted in overweight or obese individuals without identifiable etiology for liver disease, or when imaging studies suggest hepatic steatosis. NAFLD is now considered to be a component of the insulin resistance syndrome (metabolic syndrome X). Controversy exists relative to optimal recognition, diagnosis and management of these conditions, and treatment recommendations are evolving.     

Genetic risk and value

A conceptual truth about risks is that they involve a possible and future adverse effect or a negative value of some kind. The genetic risks that individuals may face in the health care setting differ in some crucial respects to other kind of risks. The aims of this paper are to analyse the notion of value in the context of genetic risk in the setting of health care, and to suggest a conception of the evaluative aspect of genetic risk that is fruitful for genetic risk information. Two influential and relevant approaches to value, preferentialism and the capability approach, are discussed in the light of certain distinctive features of genetic risk and a third, a sensibility theory of value is suggested. According to this view, the concept of risk is a so-called ‘thick’ evaluative concept that has both a world-guiding function as well as an action-guiding or normative function. It is argued that this provides a more promising way to think about genetic risks in the clinical setting.     

Genetik und Versicherung aus ökonomischer Sicht

For some years direct gene tests have been available for many diseases and nearly every week new gene mutations are found and linked with diseases. By improving the diagnostic possibilities consequences for certain insurance branches will arise. Health and life insurance in particular will perhaps face radical chances, especially concerning the acceptance of contracts. If there is a contract between a policy holder and an insurance company, it is more important whether the cost-effectiveness of genetic screening is given. Exemplary this is calculated for a population-based screening for hemochromatosis. Furthermore it is relevant, whether the population will use available gene tests. The results of a pilot study will be presented. They show that there is a market for such products and that consequences for insurance companies are likely.     

Use of a Markov Model to Estimate Long-Term Insured Lives’ Mortality Risk Associated With BRCA1 and BRCA2 Gene Mutations

Abstract

There is uncertainty regarding the degree of insurance risk associated with BRCA1/2, the gene mutations associated with breast cancer. Most reports to date have been based on high-risk populations selected from families with multiple and/or early-onset cancers; more favorable data have been reported in studies without this selection bias.

This paper discusses use of a Markov model to estimate mortality risk associated with BRCA1/2 gene mutations in female life insurance applicants. The goal is to derive a range of risk estimates based on different assumptions of breast and ovarian cancer incidence. A particular strength of the model is that transition probabilities after cancer diagnosis vary with age and cancer stage, as do excess hazard rates.

Data calculated by the model indicate that no single mortality curve characterizes risk for all life insurance applicants with a BRCA1/2 mutation. Rather, mortality risk depends on breast and ovarian cancer incidence rates and subsequent mortality rates, and on the method used to deal with competing breast and ovarian cancer incidence and mortality rates. Further refinement of risk estimates will depend on better incidence data and on resolution of complex statistical problems, such as informative censoring.

Widespread use of genetic information by insurance consumers could have important economic implications. For companies that sell individually underwritten products, profitability might decrease. Consumers might find higher prices and reduced availability, with a corresponding decrease in quantity of insurance purchased. Insurance and consumer ramifications would vary by cover, with living-benefit products, such as critical-illness insurance, most adversely affected. Societal choices are limited. Given assumptions in the cited scenario, it is likely premiums would rise and quantity of insurance purchased would decrease even with no change in existing social policy; attempted legal or regulatory remedies would further accentuate price increases and reductions in quantity purchased.     

The Genetics of Breast and Ovarian Cancer III: A new model of family history with insurance applications

Insurers’ access to genetic test results is often restricted and the only genetic information that might be collected during underwriting in some countries is family history. Previous studies have included family history in a simple way but only for diseases which have no cause other than gene mutations, because then the event ‘affected parent’ contributes all possible information short of a genetic test result. We construct a model of breast cancer (BC) and ovarian cancer (OC) — common diseases with rare genetic variants — in which the development of a family history is represented explicitly as a transition between states, hence as part of the applicant's own life history. This allows the impact of a moratorium to be modelled. We then apply this family history model to life insurance in a semi-Markov framework and to critical illness (CI) insurance in a Markov framework to: (a) estimate premium ratings depending on genotype or family history; and (b) model the potential cost of adverse selection.     

Underwriting idiopathic interstitial lung diseases

Interstitial lung disease (ILD) incorporates a large number of pathologic processes that have in the interstitial compartment of the lung. This article focuses on the diagnosis, morbidity and mortality implications of persons diagnosed with idiopathic interstitial pneumonias/fibrosis. Even within this category, the mortality and morbidity varies greatly (from months to near-normal mortality) given the specific disease present.     

Pricing Term Insurance in the Presence of a Family History of Breast or Ovarian Cancer

Abstract

We estimate the increased mortality and term life insurance costs for women who have a family history of breast or ovarian cancer. Using data from the medical literature on age-specific and family history-specific incidence rates, we develop double-decrement models to evaluate the actuarial impact of breast cancer and ovarian cancer in the family. We also calculate the increased mortality and term insurance costs for women who test positive for the BRCA1 or BRCA2 gene mutation. We find that the type of affected relative and her age at onset of the disease are key underwriting factors. We find substantial mortality increases (up to 100%) for women with two relatives with cancer and women with a first-degree relative who developed cancer at an early age. Mortality increases for women with the BRCA gene mutation reach 150%. While some females with a family history of cancer can be accepted at standard rates, others may need to be quoted substandard rates, depending on the underwriting policy of the company. Females with the gene mutation can possibly be accepted at a rate that incorporates a severe mortality surcharge.     

Cost-benefit analysis of electron beam CT as a life insurance coronary disease risk assessment tool

Electron beam CT (EBCT) or ultrafast CT is a diagnostic imaging technique that can identify calcium deposits within coronary arteries. Intra-coronary calcium is associated with coronary artery atherosclerosis. EBCT imaging has been advocated as a "better" way to screen for coronary artery disease. By producing a measure of the amount of calcium present, it may provide a non-invasive risk assessment tool that can predict the risk of future coronary events and death. Medical literature concerning identification and assessment of coronary risk using EBCT in the clinical setting is reviewed. The primary purpose is to illustrate one approach to a simple "back of the envelope" cost-benefit analysis (protective value) comparing EBCT with exercise electrocardiography as a life insurance coronary disease risk assessment tool. The performance and results of this analysis are contingent on a number of critical assumptions that are outlined in the text. The analysis limitations, and the future research required to refine the results are reviewed. With optimum levels of EBCT test performance, favorable thresholds of test costs, and long-term mortality data useful for assessment of value preservation, EBCT might prove to be a valuable risk assessment tool from a cost-benefit perspective under certain circumstances. Answers to key clinical research questions from prospective studies in asymptomatic cohorts are essential for refinement of a cost-benefit estimate.     

Exploring the interaction between technology and morality in the field of genetic susceptibility testing: A scenario study

With the rise of genomics promises and concerns have emerged about future possibilities for screening of genetic susceptibilities to common diseases in the population. In this article we start from the assumption that for a better understanding of the future ethical implications of genetic susceptibility screening we need to address the interaction between technological and moral developments in society. We introduce a techno-ethical scenario approach and show how it may help us to explore more systematically potential future interactions between technological and moral developments in the field of genetic susceptibility screening. The first step is a historical account of population screening, focussing on the ways in which emerging practices of (genetic) screening have been mediated by an evolving moral landscape in our society. Based on this history we present a techno-ethical scenario of the future, showing how technological developments may shape conditions in our society in which the introduction and use of genetic susceptibility tests more and more become a matter of private decisions, reinforcing claims to individual self-determination as a deeply rooted value in the moral landscape of our society.     

C-reactive protein--a screening test for coronary disease?

C-reactive protein (CRP) is one of a number of substances termed "acute phase reactants," biologic substances that appear in the circulation when an active inflammatory process occurs. Although traditionally used to monitor or detect major infectious or inflammatory conditions, elevations of CRP levels within the conventional range of "normals" has been intensively studied as a marker for coronary disease and risk of future coronary events. Sensitive assays that can be performed on a high-volume, commercial basis are now available. CRP appears to be a valuable marker for the prediction of future events in individuals who have known coronary artery disease. CRP has been proposed as a coronary disease-screening test for healthy individuals; however, available data suggest that use of CRP in this context may be premature. This paper reviews published research concerning CRP and the prediction of cardiovascular and total mortality risk, then outlines the current "state of the art" for the application of CRP to the risk assessment process.     

Taxation, Public Policy, and Dynamics of Unemployment

This paper provides an overview of the key issues relating to taxation, public policy and the dynamics of unemployment.It takes issue with the widely held view that generous social insurance schemes and the associated highpayroll taxes have been the major cause of the high unemployment rates which have persisted in Europe over thepast 15 years. It puts forward a framework for a theory of adjustment, based on the portfolio theory of the riskaverse firm and the efficiency wage theory of labor markets. This is used to explain why in the onset of a downturn,the hiring rate may lag the layoff rate, thus giving rise to rising unemployment rates. It is also shown to provideguidance as to policies which enhance the ability of firms to bear risks and which reduce costs of hiring and firing.The paper argues that while policies which increase severance or layoff costs may be well intended they mayactually serve to exacerbate the magnitude of employment fluctuations. Similarly, unemployment compensation,which is designed to ease the burden on those who are unemployed, may lead to higher levels of equilibriumunemployment. These programs can be restructured in ways which simultaneously ease the short-run burden ofthose thrown into unemployment, while reducing the adverse impact of these programs on the unemployment rate.