Mortality and Advances in Medicine

Mortality and Advances in Medicine Metropolitan Underwriting Discussion Group New York Jan. 28-29, 2008 J. Carl Holowaty M.D. What kind of changes do we expect in mortality in the future? “Squaring” of the Survival Curve Male U.S. Population Survival Curve 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 1934 1954 1974 1994 2004 level improv't Survival Probability 75% 50% 25% 10% 5% 1% 1934 48 66 77 84 88 94 1954 59 71 81 87 91 96 Age at Death 1974 1994 2004 61 66 68 72 77 79 81 85 87 88 91 93 91 94 96 97 99 102 flat improv't 67 80 90 98 102 110 Age 75% 50% 25% 10% 5% 1% 1934 0 0 0 0 0 0 1954 11 5 4 3 3 2 Age At Death D1934 1974 1994 2004 13 18 20 6 11 13 4 8 10 4 7 9 3 6 8 3 5 8 Percent Surviving flat improv't 19 14 13 14 14 16 0 10 20 30 40 50 60 70 80 90 100 Age Source: Human Mortality Database. University of California, Berkeley (USA), and Max Planck Institute for Demographic Research (Germany). Available at www.mortality.org (data downloaded on July 25, 2007). 3 Historical and Projected Age-Adjusted q‟s Source: Social Security Administration, Office of the Chief Actuary, Actuarial Study No. 120 Historical Mortality Trends: “Bumps in the Road”  Influenza Pandemics  1918 Spanish Flu  1957 Asian Flu  1968 Hong Kong Flu  HIV / AIDS  September 11, 2001  National Speed Limit How much can mortality improve?  Curing all cancers  3 year improvement  Eliminating all cardiovascular disease  5 year improvement  Eliminating all cancer and cardiovascular disease  ?8 year improvement  Important to align pricing with mortality expectations and track actual results closely  Need to anticipate changes in longevity for both life and annuity products. Surprises are not good!  Even if mortality projections are accurate, lack of underwriting integrity can undermine this knowledge  e.g. Inappropriate crediting or table shaving programs, high exception rates Factors affecting Mortality expectations  Changes in mortality in general and insured population affected by:      Access to medical care Socioeconomics Medical advances Cultural and lifestyle factors Environment Access to Medical Care Problem: More Than 1 in 10 Missourians Uninsured “The uninsured have worse health outcomes.” St. Louis Metropolitan Medicine July/August 2007 Condition Pediatric trauma Heart attack Insured death rate 2.1% 8.3% Uninsured Death rate 4.2% 13.1% Effects of Socioeconomics  Life expectancy (from birth) in Russia between 1990 and 1994 dropped about 6.5 years in males and about 3 years in females  Attributed to:      Rise in alcoholism Labor force turnover (job loss/stress) Increasing crime rate Income inequality Impoverishment Medical Research Through the Ages Medical Research Through the Ages Medical Research Through the Ages Medical Advances          Novel drug therapies Meta-analysis Bio-informatics and computational biology Evidence based medicine Human genome project Proteomics RNA interference (RNAi) Imaging technology Cancer screening techniques Bio-informatics and computational biology  Bio-informatics – the creation and advancement of algorithms, computational and statistical techniques and theory used to analyze biological data  Computational biology – hypothesis-driven investigation of specific biological problems (using computers) carried out with experimental or simulated data  Both of these involve the use of applied mathematics, informatics, statistics, computer science, artificial intelligence, chemistry and biochemistry to solve biological problems on a molecular level.  Primary use is in gene finding, genome assembly, sequence alignment, protein structure prediction and alignment, prediction of gene expression and proteinprotein interactions Proteomics  Def. – the large-scale study of proteins, particularly their structures and functions.  Proteins play a central role in the life of an organism and their study is instrumental in the discovery of disease biomarkers.  Proteome – the entire set of proteins produced by an organism during it‟s lifetime  Protein production is determined by the genes through mRNA. While there are 25,000 identified genes, there are over 500,000 identified proteins.  Complexity of proteins derives from mechanisms such as alternative splicing, protein modification and protein degradation.  Studies are underway to catalog all human proteins (?>2million) through the Human Proteome Organization, HUPO (http://www.hupo.org/)  The goal is to identify the human proteome and to study the interaction between the proteins  Tools include protein microarrays, X-Ray crystallogaphy, nuclear magnetic resonance, immunoaffinity chromatography followed by mass spectrometry and combinations of experimental techniques such as phage display and computational methods. RNA interference  This is a naturally occurring process that involves genome maintenance and provides protection against viruses  RNAi can block specific genes at the mRNA level  Some diseases, such as viral diseases and cancer rely on the production of messenger RNA and the proteins that they form.  Exploitation of RNAi can help identify gene function as well as potentially modify pathways that control such basic functions as insulin receptors at the cellular level, with implications for weight control and diabetes prevention Genomics  The study of an organism‟s entire genome (set of genes)  Began in the ‟80s, but the pace of work accelerated in the ‟90s. This primarily involved gene sequencing  Functional genomics involves the study of patterns of gene expression during various conditions.  Primary tools are microarray technology and bioinformatics  The first organism sequenced was a bacteriophage in 1977  Rough draft of human genome sequenced in 2001  Human genome Project was completed in 2003, with additional work done on completing the DNA sequence of each chromosome.  Now, over 1000 viruses, 200 bacteria and 20 more complex animals have been sequenced.  Genome from Dr. Craig Venter decoded (Aug. 2007) Genetic Testing                                     Some Currently Available DNA-Based Gene Tests Alpha-1-antitrypsin deficiency (AAT; emphysema and liver disease) Amyotrophic lateral sclerosis (ALS; Lou Gehrig's Disease; progressive motor function loss leading to paralysis and death) Alzheimer's disease* (APOE; late-onset variety of senile dementia) Ataxia telangiectasia (AT; progressive brain disorder resulting in loss of muscle control and cancers) Gaucher disease (GD; enlarged liver and spleen, bone degeneration) Inherited breast and ovarian cancer* (BRCA 1 and 2; early-onset tumors of breasts and ovaries) Hereditary nonpolyposis colon cancer* (CA; early-onset tumors of colon and sometimes other organs) Central Core Disease (CCD; mild to severe muscle weakness) Charcot-Marie-Tooth (CMT; loss of feeling in ends of limbs) Congenital adrenal hyperplasia (CAH; hormone deficiency; ambiguous genitalia and male pseudohermaphroditism) Cystic fibrosis (CF; disease of lung and pancreas resulting in thick mucous accumulations and chronic infections) Duchenne muscular dystrophy/Becker muscular dystrophy (DMD; severe to mild muscle wasting, deterioration, weakness) Dystonia (DYT; muscle rigidity, repetitive twisting movements) Emanuel Syndrome (severe mental retardation, abnormal development of the head, heart and kidney problems) Fanconi anemia, group C (FA; anemia, leukemia, skeletal deformities) Factor V-Leiden (FVL; blood-clotting disorder) Fragile X syndrome (FRAX; leading cause of inherited mental retardation) Galactosemia (GALT; metabolic disorder affects ability to metabolize galactose) Hemophilia A and B (HEMA and HEMB; bleeding disorders) Hereditary Hemochromatosis (HFE; excess iron storage disorder) Huntington's disease (HD; usually midlife onset; progressive, lethal, degenerative neurological disease) Marfan Syndrome (FBN1; connective tissue disorder; tissues of ligaments, blood vessel walls, cartilage, heart valves and other structures abnormally weak) Mucopolysaccharidosis (MPS; deficiency of enzymes needed to break down long chain sugars called glycosaminoglycans; corneal clouding, joint stiffness, heart disease, mental retardation) Myotonic dystrophy (MD; progressive muscle weakness; most common form of adult muscular dystrophy) Neurofibromatosis type 1 (NF1; multiple benign nervous system tumors that can be disfiguring; cancers) Phenylketonuria (PKU; progressive mental retardation due to missing enzyme; correctable by diet) Polycystic Kidney Disease (PKD1, PKD2; cysts in the kidneys and other organs) Adult Polycystic Kidney Disease (APKD; kidney failure and liver disease) Prader Willi/Angelman syndromes (PW/A; decreased motor skills, cognitive impairment, early death) Sickle cell disease (SS; blood cell disorder; chronic pain and infections) Spinocerebellar ataxia, type 1 (SCA1; involuntary muscle movements, reflex disorders, explosive speech) Spinal muscular atrophy (SMA; severe, usually lethal progressive muscle-wasting disorder in children) Tay-Sachs Disease (TS; fatal neurological disease of early childhood; seizures, paralysis) Thalassemias (THAL; anemias - reduced red blood cell levels) Timothy Syndrome (CACNA1C; characterized by severe cardiac arrhythmia, webbing of the fingers and toes called syndactyly, autism) Gene Therapy  A technique for correcting defective genes responsible for disease development  Involves the use of vectors such as viruses to deliver genetic material to target cells.  The FDA has not yet approved any human gene therapy product for sale.  Still some major technical problems to be solved.  Ethical issues. Gene Therapy Aug. 2007 – University of Toronto  Lou Gehrig‟s disease (amyotrophic lateral sclerosis), ALS – 5 year life expectancy  Caused by mutant genes that make defective proteins that lead to muscle cell paralysis and death  Researchers have developed a „customized‟ antibody that searches out and destroys the defective protein Cultural and Lifestyle Factors  Diet  Exercise Environment  Access to clean water and air  Pollution  Ozone depletion  Heavy-metal contamination  Nutritious and safe food issues Mortality: A Balancing Act  Pros:  Medical advances in treatment  Public education regarding benefits of lifestyle factors  Disease prevention -Immunization and vaccination  Cons  Mutation of viruses into deadly contagions  e.g. Avian flu http://news.bbc.co.uk/2/hi/health/6959583.stm WHO warns of global epidemic risk Infectious diseases are spreading faster than ever before, the WHO annual report says. “It would be extremely naïve and complacent to assume that there will not be another disease like AIDS, another Ebola, or another SARS, sooner or later,…” New diseases are emerging at “historically unprecedented” rate of one per year.  Development of drug resistance  e.g. T.B., staphylococcus  Lack of health care  Lifestyle  e.g. obesity/diabetes/sedentary behavior How do we assess Mortality Risk  Underwriting Practices  Our clients  Our own  Guidelines to risk stratification  Rational approach  Adherence to guidelines Refinement of Guidelines  New criteria can be applied for more accurate evaluation of select populations within the insured population  Prognostic factors vary by age  e.g. Older age underwriting – need to measure cognitive function, physical function and social engagement as unique markers for mortality  Must choose adequate screening methods and assign appropriate debits or credits based on results New Underwriting Tools  Lab tests  E.g. NT- ProBNP (a serum marker for congestive heart failure) Success will be measured by how this test is marketed and used. Important to not overestimate the mortality gains, especially if this test is used a substitute for other tests, rather than an additional test.  Old age underwriting specialized testing Questions?