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Letter From the Editor
What's New? AI versus superbug, AI cuts waste in organ donations, and the latest research updates.
Underwriting Updates GUM’s guidelines and information on mental health
Case ReView A case of neuroendocrine tumors
Claims Updates Claims management demands deep technical expertise and a human touch
Longer Life Foundation
RGA's Global Medical Newsletter
Balancing Pills and Golden Years: Understanding polypharmacy in older adults by Dr. Sheetal Salgaonkar Early-Onset Colorectal Cancer and Implications for the Life Insurance Industry by Dr. Russell Hide Obstructive Sleep Apnea: A review of current treatment options by Dr. Jeffrey Henderson
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Dr. Adela Osman
Senior Vice President, Head of Global Medical
adela.osman@rgare.com
I am pleased to share the latest installment of RGA’s medical newsletter, packed with valuable insights on a variety of medical issues impacting the insurance industry. In our feature articles, Dr. Sheetal Salgaonkar highlights polypharmacy and its prevalence among seniors; Dr. Russell Hide discusses early-onset colorectal cancer and its impact on life insurers; and Dr. Jeffrey Henderson explores obstructive sleep apnea treatment and its impact on mortality. Additional insights in this volume: Case ReView by Dr. Sheetal Salgaonkar focuses on the underwriting considerations for neuroendocrine tumors in a critical illness case. In Health View, Dr. Steve Woh looks at AI-enabled breakthroughs to address antimicrobial resistance and applying a machine-learning model to improve organ donation efficiency. Our Research Watch summarizes how retinal scans can be used to assess cardiovascular risk and biological aging, how cannabis use can be linked to increased risk of diabetes, and how mRNA vaccines can impact the outcome of cancer immunotherapy. The Underwriting Update provides links to revised guidelines for autism spectrum disorder, feeding and eating disorders, and bipolar disorder. Our Claims Update spotlights the training and support available to RGA clients, especially for mental health. I remain appreciative for the contributions and input from our Assistant Editors and RGA Asia Medical Directors, Dr. Karneen Tam and Dr. SiNing Zhao. As always, we invite you to provide feedback on ReFlections by using the star ratings to evaluate articles and submit comments for topics you would like to see in future volumes. Thank you, Adela Osman
Welcome to the February 2026 edition of ReFlections.
ReFlections
From the Editor
In this issue
Balancing Pills and Golden Years: Understanding polypharmacy in older adults
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Underwriting Updates GUM’s guidelines and information on a variety of disorders
Case ReView A Case of neuroendocrine tumors
Obstructive Sleep Apnea: A review of current treatment options
Dr. Karneen Tam, MBBCH Regional Medical Director Asia Markets
Dr. SiNing Zhao, MBBS, FANZCA, FHKCA, FHKAM Regional Medical Director Asia Markets
Assistant Editors
Early-Onset Colorectal Cancer and Implications for the Life Insurance Industry
Advances in modern healthcare have significantly extended average life spans, but increased longevity presents new challenges in the care of older adults, especially in managing multiple chronic diseases. As people age, they often develop long-term conditions such as diabetes, hypertension, arthritis, and heart disease, increasing the need for multiple medications at once – a practice known as polypharmacy. While this approach can be essential and beneficial, it also introduces significant risks that may compromise quality of life, increase healthcare utilization, and affect mortality. Evaluating these factors is particularly important in the context of assessing risk profiles in older lives for insurance underwriting purposes.
Introduction
References
Masnoon N, Shakib S, Kalisch-Ellett L, et al. What is polypharmacy? A systematic review of definitions. BMC Geriatr 17, 230 (2017). https://doi.org/10.1186/s12877-017-0621-2 O’Dwyer M, Peklar J, McCallion P, et al. Factors associated with polypharmacy and excessive polypharmacy in older people with intellectual disability differ from the general population: a cross-sectional observational nationwide study BMJ Open 2016;6:e010505. doi: 10.1136/bmjopen-2015-010505 Delara M, Murray L, Jafari B, et al. Prevalence and factors associated with polypharmacy: a systematic review and meta-analysis. BMC Geriatr 22, 601 (2022). https://doi.org/10.1186/s12877-022-03279-x Lee EA, Brettler JW, Kanter MH, Steinberg SG, Khang P, Distasio CC, Martin J, Dreskin M, Thompson NH, Cotter TM, Thai K, Yasumura L, Gibbs NE. Refining the Definition of Polypharmacy and Its Link to Disability in Older Adults: Conceptualizing Necessary Polypharmacy, Unnecessary Polypharmacy, and Polypharmacy of Unclear Benefit. Perm J. 2020;24:18.212. doi: 10.7812/TPP/18.212; epub 2019 Dec 11. PMID: 31905333; PMCID: PMC6972545. Li Y, Zhang X, Yang L, Yang Y, Qiao G, Lu C, Liu K. Association between polypharmacy and mortality in the older adults: A systematic review and meta-analysis. Arch Gerontol Geriatr. 2022 May-Jun;100:104630. doi: 10.1016/j.archger.2022.104630; epub 2022 Jan 28. PMID: 35101709. Chae J, Cho HJ, Yoon SH, Kim DS. The association between continuous polypharmacy and hospitalization, emergency department visits, and death in older adults: a nationwide large cohort study. Front Pharmacol. 2024 Jul 31;15:1382990. doi: 10.3389/fphar.2024.1382990; PMID: 39144630; PMCID: PMC11322047. Costanzo S, Di Castelnuovo A, Panzera T, De Curtis A, Falciglia S, Persichillo M, Cerletti C, Donati MB, de Gaetano G, Iacoviello L; Moli-sani Investigators. Polypharmacy in Older Adults: The Hazard of Hospitalization and Mortality is Mediated by Potentially Inappropriate Prescriptions, Findings From the Moli-sani Study. Int J Public Health. 2024 Oct 24;69:1607682. doi: 10.3389/ijph.2024.1607682; PMID: 39513180; PMCID: PMC11540657. Dhalwani NN, Fahami R, Sathanapally H, Seidu S, Davies MJ, Khunti K. Association between polypharmacy and falls in older adults: a longitudinal study from England. BMJ Open. 2017 Oct 16;7(10):e016358. doi: 10.1136/bmjopen-2017-016358; PMID: 29042378; PMCID: PMC5652576. Ekram ARMS, Woods RL, Ryan J, Espinoza SE, Gilmartin-Thomas JFM, Shah RC, Mehta R, Kochar B, Lowthian JA, Lockery J, Orchard S, Nelson M, Fravel MA, Liew D, Ernst ME. The association between polypharmacy, frailty and disability-free survival in community-dwelling healthy older individuals. Arch Gerontol Geriatr. 2022 Jul-Aug;101:104694. doi: 10.1016/j.archger.2022.104694; epub 2022 Mar 23. PMID: 35349875; PMCID: PMC9437977.
About the author
Dr. Sheetal Salgaonkar is a Vice President and Global Medical Director with RGA and a member of RGA’s Global Medical team. Based in Mumbai, India, she provides underwriting and claims consultation for RGA’s regional offices in the International division and is involved in product development, medical underwriting training, and the development of guidelines for RGA’s Global Underwriting Manual. Dr. Salgaonkar has been a part of the Federation of Indian Chambers of Commerce & Industry’s Task Force for Critical Illness and was a member of the subcommittee for Policy Formulation on Financial Inclusion of Persons with Disabilities for India’s insurance industry. She is also Treasurer of the Indian Insurance Medical Officer’s Association (IMOK) and was the scientific chair of the International Committee for Insurance Medicine’s 2019 meeting, which was held in Mumbai. She has made significant contributions to the course curriculum of the Underwriting Diploma and the Advanced Underwriting Diploma, a joint initiative of the Association of Insurance Underwriters and the Insurance Institute of India.
Dr. Sheetal Salgaonkar
Vice President, Global Medical Director
ssalgaonkar@rgare.com
Polypharmacy increases the risk of functional decline, cognitive impairment, falls, and hospitalization – all major contributors to long-term disability.
Polypharmacy, typically defined as the use of five or more medications daily, is widespread among seniors, with a prevalence of about 37% in those over age 65. There is a clear, dose-dependent relationship between the number of medications and negative health outcomes like mortality, emergency visits, hospital admissions, falls, frailty, and loss of disability-free survival. Polypharmacy in older adults is a red flag for underwriters, signaling the need for a thorough, individualized assessment. By closely evaluating medication profiles, adherence, and follow-up care, underwriters can better estimate risk and make more-informed decisions.
Key takeaways
Risks associated with polypharmacy 1. Mortality risk Many studies confirm a dose-dependent, independent association between polypharmacy and increased mortality risk, even after adjusting for other factors like comorbidities and demographics. A meta-analysis of more than 24 studies found that polypharmacy increases the risk of death, with a relative risk of 1.28, meaning a 28% higher risk of all-cause mortality compared to those not on polypharmacy regimens.5 A large population-based study of nearly 3 million older adults found that polypharmacy (≥5 medications for over 180 days) was associated with a 63% increased risk of death (adjusted hazard ratio HR: 1.63) compared to those with no polypharmacy. For hyper-polypharmacy (≥10 medications), the risk of death was more than doubled to HR: 2.57.6 2. Hospitalization risk Polypharmacy significantly increases the likelihood of emergency visits and hospital admissions. One study showed that polypharmacy patients were 1.29-1.33 times more likely to be hospitalized or to visit the emergency room than those without polypharmacy – even after adjusting for the number of comorbidities.6 Chronic polypharmacy regimens (long-term use of five or more medications with higher daily doses) are linked to up to 61% increased hazard of hospitalization compared to those not on polypharmacy.7 Adverse drug reactions, drug-drug interactions, and inappropriate prescriptions are common in polypharmacy and play a significant role in increased hospitalizations. 3. Disability and frailty Polypharmacy contributes to increased rates of falls, disability, and frailty. A longitudinal study published in BMJ found the rate of falls was 21% higher in people with polypharmacy compared with people without. Using a ≥four drug threshold, the fall rate was 18% higher in people with polypharmacy; using a ≥10 drug threshold, the rate was 50% higher over a two-year period.8 Polypharmacy is also strongly associated with an increased risk of disability and loss of disability-free survival (DFS), especially in older adults. Frail individuals exposed to polypharmacy face a hazard ratio (HR) for reduced DFS of approximately 4.24, meaning they are over four times more likely to experience death, dementia, or persistent physical disability compared to non-frail individuals without polypharmacy. Even pre-frail individuals with polypharmacy have an HR of about 2.21 for these outcomes. Overall, polypharmacy increases the risk of functional decline, cognitive impairment, falls, and hospitalization – all major contributors to long-term disability. Studies link polypharmacy to a greater likelihood of developing geriatric syndromes, which directly contribute to increasing rates of disability.9
Definition and prevalence There is no clear or universal definition of polypharmacy, but it typically refers to the concurrent use of five or more medications daily.1 This includes prescription drugs, over-the-counter medicines, and dietary supplements. Excessive polypharmacy (EPP) refers to concurrent use of 10 or more daily medications.2 Studies indicate that polypharmacy is widespread among older adults. A meta-analysis of 54 studies estimated an overall prevalence of 37% in individuals over 65 years of age.3
Classification of polypharmacy Polypharmacy can be categorized based on the necessity and balance of risks versus benefits:4 Necessary polypharmacy (NP) – The use of multiple medications that demonstrably improve health outcomes, maintain functional ability, and provide clear clinical benefit, where benefits outweigh risks. Unnecessary polypharmacy (UP) – Involves medications that offer minimal or no clinical advantage while increasing the likelihood of adverse outcomes. These drugs should be avoided or deprescribed when possible. Polypharmacy of uncertain benefit (PUC) – Cases where the risk-benefit ratio is unclear due to insufficient evidence. Such cases warrant individualized evaluation and shared decision-making between clinician and patient.
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Underwriting implications Underwriters should note the number, dosage, and names of medications of all prescribed and over-the-counter medications. Medication profiles may reveal underlying diseases and their severity, even when not disclosed in medical histories. Attention must be paid to reported adverse drug reactions (ADRs) and interactions between medications or between drugs and existing diseases. Medication adherence is an important indicator of stability; cognitive impairment and memory issues can reduce compliance and increase risk. Regular medical follow-up should be viewed favorably, as it ensures periodic medication review and reduces inappropriate prescribing, mitigating risk.
Conclusion Polypharmacy is a common and complex issue in older adults, significantly influencing mortality, hospitalization, and disability risks. Its presence often reflects the burden of multiple chronic diseases and challenges in maintaining optimal care. For underwriters, reviewing medication patterns provides crucial insight into health stability and future risk potential. Continuous medication review and appropriate management can help mitigate these risks and enhance the quality of life in senior populations.
Colorectal cancer incidence is rising in individuals under age 50, with rates rising about 30% over two decades, creating significant underwriting and risk assessment implications for the life insurance industry. Some guidelines now recommend routine screening starting at age 45, and advances in screening and diagnostic tests are improving early detection in younger populations. Insurers should consider underwriting models that incorporate lifestyle, genetic (when possible), and screening adherence data, as well as developing products that incentivize early detection and wellness, to mitigate risk and enhance product value.
Colorectal cancer rates in people under 50 have risen steadily over the past two decades, with increases of 30% in the age group.1 Studies indicate a year-on-year increase of approximately 2% in incidence among adults ages 20 to 50.2,11 Although absolute case numbers remain lower than in older populations, the growth trend is significant and unlikely to reverse without intervention.3 Young-onset cases often present at a more advanced stage. Symptoms can often be mistaken for benign conditions like hemorrhoids or irritable bowel syndrome, delaying diagnosis. For life insurers, these delays increase morbidity and mortality risks not captured by traditional age-based underwriting models.
Epidemiology of early-onset colorectal cancer
Dr. Russell Hide is a medical advisor with RGA, specializing in underwriting and claims assessment support for South Africa and the EMEA region. Russell has more than 25 years of experience in the insurance and reinsurance sectors, as well as a clinical background in general practice. He joined RGA in 2016 and is based in Cape Town. He holds an MBBCh degree from the University of the Witwatersrand.
Dr. Russell Hide
Medical Officer
Russell.Hide@rgare.com
The rise of early-onset colorectal cancer necessitates a reassessment of underwriting practices.
Historically considered a disease of older adults, colorectal cancer is now increasingly diagnosed in individuals under the age of 50. This rise in early-onset colorectal cancer (EOCRC) has direct implications for the life insurance industry, impacting underwriting, risk assessment, product design, and wellness strategies. EOCRC refers to colorectal cancer diagnosed in people younger than 50. Understanding the factors driving young-onset cases – including rising incidence in younger groups, lifestyle influences such as obesity and diet, and advances in genetic screening and early detection – enable insurers to refine risk assessment and improve product design. Strategies include evidence-based underwriting rules, pricing that reflects emerging risks, and screening incentives and wellness-linked benefits to promote early detection and reduce claims exposure.
Implementing early-onset screening programs presents several challenges: Privacy and data security – Using genetic and other personal data for underwriting purposes must comply with local and general privacy regulations and laws. Anti-selection – Applicants, aware of an increased risk, may selectively seek specific insurers or policies, skewing the risk pool. Medical uncertainty – Recently developed screening technologies and changes in underwriting guidelines may result in challenges for risk rating and pricing. Operational complexity – Incorporating new data sources, updating underwriting systems, and retraining underwriters and support staff require additional resources.
Challenges
Siegel RL, Torre LA, Soerjomataram I, et al. Global patterns and trends in colorectal cancer incidence in young adults. Gut. 2019; 68:2179–85. doi: 10.1136/gutjnl-2019-319511 Siegel RL, Miller KD, Goding Sauer A, et al. Colorectal cancer statistics, 2023. CA Cancer J Clin.2023;73(3):233–289. doi:10.3322/caac.21715 Chambers AC, Dixon SW, White P, et al. Demographic trends in the incidence of young-onset colorectal cancer: a population-based study. Br J Surg. 2020;107(5):595–605. doi:10.1002/bjs.11486 Turk A, Mondaca S, Nervi B, et al. Early-onset colorectal cancer: from genetic discovery to clinical innovation. ASCO Educ Book. 2025;45: e473618. doi:10.1200/EDBK-25-473618 de Klaver W, Wisse PHA, van Wifferen F, Bosch LJW, Jimenez CR, van der Hulst RWM, Fijneman RJA, Kuipers EJ, Greuter MJE, Carvalho B, Spaander MCW, Dekker E, Coupé VMH, de Wit M, Meijer GA. Clinical Validation of a Multitarget Fecal Immunochemical Test for Colorectal Cancer Screening: A Diagnostic Test Accuracy Study. Ann Intern Med. 2021 Sep;174(9):1224-1231. doi: 10.7326/M20-8270; epub 2021 Jul 20. PMID: 34280333. US Preventive Services Task Force. Screening for Colorectal Cancer: US Preventive Services Task Force Recommendation Statement. JAMA. 2021;325(19):1965–1977. doi:10.1001/jama.2021.6238 American Cancer Society. Colorectal Cancer Screening Guidelines. https://www.cancer.org/cancer/colon-rectal-cancer/detection-diagnosis-staging/screening- tests-used.html Accessed July 2025. Rex DK, Boland CR, Dominitz JA, et al. Colorectal Cancer Screening: Recommendations for Physicians and Patients from the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology. 2017;153(1):307–323. doi: 10.1053/j.gastro.2017.04.001 Sarah E. Coughlin et al. Multigene Panel Testing Yields High Rates of Clinically Actionable Variants Among Patients With Colorectal Cancer. JCO Precis Oncol 6, e2200517(2022). DOI:10.1200/PO.22.00517 Imperiale TF, Ransohoff DF, Itzkowitz SH, et al. Multitarget stool DNA testing for colorectal- cancer screening. N Engl J Med. 2014;370(14):1287–1297. doi:10.1056/NEJMoa1311194 PDQ® Screening and Prevention Editorial Board. PDQ Colorectal Cancer Screening. Bethesda, MD: National Cancer Institute. Updated 04/10/2025. Available at: https://www.cancer.gov/types/colorectal/hp/colorectal-screening-pdq Accessed 11/21/2025. [PMID: 26389266]
Risk factors for early-onset disease
Multiple factors contribute to increased incidence of colorectal cancer in younger adults: Diet and lifestyle influences, societal trends High consumption of red and processed meats Low fiber intake and decreased fruit and vegetable consumption Sedentary behavior and obesity Genetic predispositions Familial adenomatous polyposis and Lynch syndrome, and genetic mutations in various genes. e.g., NTHL1, POLD1, POLE and RNF434 Family history of colorectal or endometrial cancer Environmental exposures and co-morbidities Antibiotic use influencing gut microbiome balance Chronic inflammation from conditions like inflammatory bowel disease Recognizing these risk factors can help insurers update underwriting practices and adjust predictive models to more accurately identify high-risk applicants, regardless of age.
Revision of screening guidelines
In response to rising early-onset cases, several health organizations have lowered screening age thresholds: The United States Preventive Services Task Force (USPST) now recommends routine screening starting at age 45.6 The American Cancer Society advises average-risk adults to start screening at 45 and to consider earlier screening when additional risk factors are present.7 Some European nations and healthcare networks are testing guidelines for screening adults at 40, particularly if they have family history or metabolic syndrome.8
Advances in screening methods
Traditional colonoscopy remains the gold standard, but recent technological advances have expanded options for early detection: Fecal immunochemical test (FIT) – A non-invasive stool test that detects occult blood. Frequent testing tends to increase acceptance and compliance by younger adults who are reluctant to undergo more invasive colonoscopy. Multi-target stool (mt-sDNA) testing combines DNA markers with FIT to improve detection rates for precancerous lesions and early-stage cancers.5 CT colonography (virtual colonoscopy) – Radiologic imaging that visualizes the colon. It offers a safer, non-invasive alternative to colonoscopy but requires bowel preparation similar to colonoscopy and specialized equipment. Capsule endoscopy – Swallowed camera capsule that captures internal images of the gastrointestinal tract. Currently used mainly for small-bowel diseases, its role in colorectal screening is being considered. Blood-based biomarkers (liquid biopsy) – Tests that detect circulating tumor DNA or methylated DNA fragments. Germline multigene panel testing (MGPT) identified a clinically actionable pathogenic germline variant in 14% of CRC patients in one study and is now recommended universally for all EOCRC patients’ cases.9 Machine-learning-enabled liquid biopsy platforms combine DNA methylation sequencing with fragment analysis to detect tumor indicators at very low titers.10 Together, these advances promise to shift detection toward preclinical phases in younger populations. A comparison of various colorectal carcinoma screening tools.11
Underwriting implications
Earlier screening and rising young-onset incidence may impact underwriting practices in several ways: Improved risk stratification – Combining family history, lifestyle factors, and screening protocol adherence provides a more accurate risk profile than age alone. Adjusted premium models – Younger applicants with increased risk factors may require modified pricing or adjusted benefits. Those who follow recommended screening protocols and maintain healthy lifestyle practices could be offered more favorable assessments. New data sources – Digital health records, wearable device data, and off-the-shelf genetic tests (used in underwriting only when regulations permit) can offer real-time risk indicators, enabling more precise selection and pricing decisions. Adopting underwriting models that evolve with medical guidelines ensures insurers remain competitive and avoid adverse selection. Underwriters should be encouraged to apply enhanced risk stratification practices while remaining aware of the risks of anti-selection and information asymmetry.
Product innovation and strategic opportunity
Beyond pricing, life insurers can develop products and services that support early detection and healthier outcomes: Screening encouragement – Policies that cover or reimburse the cost of screening colonoscopies, FIT kits, or advanced biomarker tests. Wellness incentives – Rewarding policyholders for completing recommended screenings or maintaining healthy lifestyles through discounted premiums or annual payback bonus incentives. Educational platforms – Webinars and personalized communications to educate and increase awareness of early-onset colorectal cancer symptoms and available screening options. These value-added options can increase customer satisfaction, improve retention, and position insurers as proactive risk managers. Implementing new technologies and applying them can turn a risk trend into a strategic competitive advantage for insurers willing to adapt.
FIT 70%-80% Low Annual
Modality Sensitivity (Early Stage) Invasiveness Frequency
Colonoscopy >95% High Every 10 years
mt-sDNA 90% Low Every 3 years
CT Colonography 90% Moderate Every 5 years
Blood Biomarkers 60%-80% Low Annual or as prescribed
Tracking and understanding the sensitivity, specificity, cost, and frequency requirements of each screening method enables insurers to review underwriting requirements and guide applicants and policyholders toward the most effective, accessible options.
The rise of early-onset colorectal cancer necessitates a reassessment of underwriting practices. Insurers must apply the latest epidemiologic data and screening innovations to refine risk assessment, product design, and wellness strategies. This will not only mitigate risk exposure, but it also can help a younger demographic detect and manage disease earlier, improving survival rates and quality of life. Now is the time to revisit underwriting guidelines, expand screening incentives, and build partnerships that advance early detection. Insurers who adopt such practices will strengthen market position and positively contribute to reversing the trend of early-onset colorectal cancer.
Conclusion
Obstructive sleep apnea is a common sleep-related breathing disorder, with significant mortality implications in those with severe disease. Observational studies of treated obstructive sleep apnea suggest reduced all-cause and cardiovascular mortality, while reliable randomized controlled trials generally report neutral findings. Longer studies, with better characteristics and inclusion criteria, are needed. Understanding the current treatment options, and their potential to improve mortality, is important to assess underwriting risk.
Peppard PE, Young T, Barnet JH, Palta M, Hagen EW, Hla KM. Increased prevalence of sleep-disordered breathing in adults. Am J Epidemiol. 2013;177(9):1006. Epub 2013 Apr 14. Sönmez I, Vo Dupuy A, Yu KS, Cronin J, Yee J, Azarbarzin A. Unmasking obstructive sleep apnea: Estimated prevalence and impact in the United States. Respir Med. 2025 Nov;248:108348. doi: 10.1016/j.rmed.2025.108348; epub 2025 Sep 14. PMID: 40957495. American Academy of Sleep Medicine. International Classification of Sleep Disorders, 3rd ed, text revision, American Academy of Sleep Medicine, 2023. Fu Y, Xia Y, Yi H, Xu H, Guan J, Yin S. Meta-analysis of all-cause and cardiovascular mortality in obstructive sleep apnea with or without continuous positive airway pressure treatment. Sleep Breath. 2017 Mar;21(1):181-189. doi: 10.1007/s11325-016-1393-1; epub 2016 Aug 8. PMID: 27502205 Carneiro-Barrera A, Amaro-Gahete FJ, Guillén-Riquelme A, et al. Effect of an Interdisciplinary Weight Loss and Lifestyle Intervention on Obstructive Sleep Apnea Severity: The INTERAPNEA Randomized Clinical Trial. JAMA Network Open. 2022;5(4):e228212. doi:10.1001/jamanetworkopen.2022.8212 Malhotra A, Heilmann CR, Banerjee KK, Dunn JP, Bunck MC, Bednarik J. Weight reduction and the impact on apnea-hypopnea index: A systematic meta-analysis. Sleep Med. 2024;121:26. Epub 2024 Jun 15. PMID 38908268. Lisan Q, Van Sloten T, Vidal PM, Rubio JH, Heinzer R, Empana JP. Association of Positive Airway Pressure Prescription with Mortality in Patients with Obesity and Severe Obstructive Sleep Apnea: The Sleep Heart Health Study. JAMA Otolaryngol Head Neck Surg. 2019 Apr 11;145(6):509–515. doi: 10.1001/jamaoto.2019.0281; PMCID: PMC6583022 PMID: 30973594. Ramar K, Dort LC, Katz SG, et al. Clinical Practice Guideline for the Treatment of Obstructive Sleep Apnea and Snoring with Oral Appliance Therapy: An Update for 2015. J Clin Sleep Med. 2015 Jul 15;11(7):773-827. MacKay S, Carney AS, Catcheside PG, et al. Effect of Multilevel Upper Airway Surgery vs Medical Management on the Apnea-Hypopnea Index and Patient-Reported Daytime Sleepiness Among Patients with Moderate or Severe Obstructive Sleep Apnea: The SAMS Randomized Clinical Trial. JAMA. 2020;324(12):1168–1179. doi:10.1001/jama.2020.14265 Alrubasy WA, Abuawwad MT, Taha MJJ, Khurais M, Sayed MS, Dahik AM, Keshu N, Abdelhadi S, Serhan HA. Hypoglossal nerve stimulation for obstructive sleep apnea in adults: An updated systematic review and meta-analysis. Respir Med. 2024 Nov-Dec;234:107826. doi: 10.1016/j.rmed.2024.107826; epub 2024 Oct 12. PMID: 39401661 Gottlieb DJ, Punjabi NM. Diagnosis and Management of Obstructive Sleep Apnea: A Review. JAMA. 2020;323(14):1389–1400. doi:10.1001/jama.2020.3514 Malhotra A, Grunstein RR, Fietzes’ I, et al. Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity. NEJM. 2024;391(13):1193-1205. doi:10.1056/NEJMoa2404881 Wu, Jheng-Yan et al Clinical Impact of Tirzepatide on Patients with OSA and Obesity. CHEST, Volume 168, Issue 3, 785–796. Luu S, Chan DECY, Marshall NS, Phillips CL, Grunstein RR, Yee BJ. Pharmacotherapy for obstructive sleep apnea: a critical review of randomized placebo-controlled trials. Sleep Med Rev. 2025 Sep 12;84:102169. doi: 10.1016/j.smrv.2025.102169; epub ahead of print. PMID: 40974973.
Obstructive sleep apnea is associated with increased all-cause and cardiovascular mortality, particularly with severe OSA.
Part II: Lewy Body Dementias
Obstructive sleep apnea, or OSA, is the most common sleep-related breathing disorder, with an estimated prevalence of 15% in males and 5% in females in the US. Globally, an estimated 425 million people age 30 to 69 have moderate to severe OSA. Prevalence increased over recent decades, rising from 11% of males and 4% of females in 1990 to 14% and 5% in 2010.1 A more recent review suggests that upward of 32.4% of US adults aged 20 or older have OSA.2 The American Academy of Sleep Medicine defines OSA as either of the following: Obstructive Respiratory Disturbance Index (RDI) ≥15 events per hour of sleep, or Obstructive RDI >5 events per hour with symptoms such as sleepiness, fatigue, insomnia, gasping, choking, snoring, or impaired sleep-related quality of life. RDI, as measured on a polysomnogram, reflects the hourly number of obstructive apneas, obstructive hypopneas, and respiratory effort-related arousals (RERA). The Apnea-Hypopnea Index (AHI), commonly used in research articles, measures obstructive apneas and obstructive hypopneas per hour.3 Obstructive sleep apnea is divided into categories based on the number of AHI events: Mild OSA, with an AHI of 5-14.9 events/hour Moderate OSA, with an AHI of 15-30/hour Severe OSA, with an AHI of >30/hour OSA commonly coexists with conditions such as congestive heart failure, atrial fibrillation, pulmonary hypertension, hypertension, end-stage renal disease, chronic lung disease, asthma, chronic obstructive pulmonary disease, stroke, pregnancy, and hypothyroidism. Obstructive sleep apnea is associated with increased all-cause and cardiovascular mortality, particularly with severe OSA. In a meta-analysis from Fu et al., hazard ratios (HR) for all-cause mortality was 1.19 for mild OSA, 1.28 for moderate OSA, and a statistically significant 2.13 for severe OSA. Cardiovascular mortality HRs were 1.24, 2.05, and 2.73, respectively.4 These findings align with earlier research. Given the increasing prevalence of OSA, and the known mortality of OSA, particularly severe OSA, understanding treatment modalities and their effect on OSA is increasingly important.
Randomized controlled trials (RCT) and clinical guidelines on OSA management recommend weight loss. A 5%-10% reduction in body weight is associated with significant decreases in AHI, symptom improvement, and, in some cases, remission of OSA, particularly with weight loss ≥10%. For example, in the INTERAPNEA trial, substantial weight loss led to a 51% reduction in AHI at eight weeks and 57% at six months, with nearly 30% of participants achieving complete remission of OSA at 6 months.5 A meta-analysis published in Sleep Medicine showed that a BMI reduction of 10% was associated with a greater than 20% reduction in AHI; and a 20% reduction in BMI resulted in a 57% reduction in AHI.6 Direct evidence of weight loss impact on the mortality of OSA is limited, but improvements in OSA severity and overall cardiometabolic health suggest a likely reduction in mortality risk.
Weight loss
Positive airway pressure therapy, or PAP, is considered the gold-standard therapy for adults with OSA. PAP prevents obstructive events due to upper airway collapse by maintaining a positive pharyngeal airway pressure that keeps the airway open. Most experts recommend starting PAP therapy when: AHI or RDI ≥5 with symptoms or if they are considered mission-critical workers (airline employees, professional drivers), or AHI or RDI ≥15 (i.e., moderate OSA). These recommendations are supported by RCTs in this population showing that PAP reduces obstructive events and daytime sleepiness, lowers motor vehicle crash risk, and improves systolic blood pressure (BP) and Quality of Life scores (QoL). Those with severe OSA are most likely to benefit. In the 2019 Sleep Heart Health Study, continuous PAP (CPAP) significantly improved OSA severity (-23 events per hour), Epworth Sleepiness Scale score, and multiple blood pressure parameters, compared to no PAP.7 Long-term adherence is critical. Studies report 65%-80% adherence at four years, with some smaller studies showing adherence rates as low as 45%. Discomfort is the most common reason for decreased adherence.8 Observational studies have shown that reducing AHI in OSA is associated with reduced mortality, particularly in those with severe OSA.6 However, RCTs have not definitively proven that AHI reduction lowers mortality. A 2025 meta-analysis of 10 RCTs and 20 observational studies found significantly lower all-cause mortality in observational PAP users (HR 0.63), while RCTs did not reach statistical significance. Authors of this study and others have suggested that duration of follow-up, under-powered sample sizes, and restrictive inclusion/exclusion criteria in the RCTs may contribute to the neutral RCT findings.
Positive airway pressure therapy (PAP)
Several types of oral devices are available, the most common being the mandibular advancement device (MAD). MADs are alternatives to PAP for mild to moderate OSA, or for patients with PAP intolerance. Studies show adherence may be higher with MADs, particularly in younger adults with lower BMI. They are not indicated for severe OSA, due to lack of efficacy. In studies, PAP is generally superior to MADs in AHI reduction and oxygen desaturation indices. However, MADs appear to be noninferior to PAP in reducing cardiovascular risk factors such as 24-hour ambulatory blood pressure measurements and QoL. Custom-made devices are associated with improved cardiovascular outcomes compared to commercially available off-the-shelf devices. Adverse aspects of the oral appliances include cost (generally $1,000-$2,000 USD) and myofascial discomfort.8
Oral appliances
Surgery is used as primary therapy for OSA when a fixed, surgically correctible airway obstruction is responsible for the apnea (e.g., severe tonsillar hypertrophy). However, surgery is usually reserved as second-line therapy for OSA, for patients with PAP intolerance, or as adjunctive therapy in conjunction with PAP or an oral appliance. The most common upper airway surgery is uvulopalatopharyngoplasty (UPPP), as upper pharyngeal obstruction is the most common anatomic airway abnormality. Modern UPPP techniques typically involve repositioning and restructuring the soft palate and related structures to reduce obstruction. Reported success rates for UPPP range from 30% to 80%, with success defined as >=50% reduction in AHI and a post-surgery AHI of <20 events per hour. The SAMS study, which used modified UPPP with tongue volume reduction techniques, demonstrated a significant reduction in AHI of nearly 28 events per hour (from 47.9 to 20.8), compared with a reduction of approximately 10 events per hour in the medical control group (45.3 to 34.5). Complete resolution of OSA (<10) occurred in 26% of surgical patients. Unfortunately, failure rates are estimated at about 50%, often due to persistent anatomic obstruction. Long-term effects of modern surgical techniques include swallowing difficulties and vocal changes or globus sensation, although most patients report satisfaction.9
Upper airway surgery
Approved in the US in 2014, the hypoglossal nerve stimulator (HGNS) is a second-line therapy for moderate to severe OSA in adults who are unable to tolerate or have failed PAP therapy, in those with AHIs in the 15-65 events per hour range and BMI ≤32-35 kg/m2. The implanted neurostimulator stimulates the hypoglossal nerve at initiation of inspiration, causing tongue anterior protrusion and stiffening to reduce upper airway collapse during sleep. Multiple studies show a significant reduction in AHI and oxygen desaturations, as well as improved QoL. For example, the Inspire device, the most widely studied and FDA-approved system, reduces AHI by approximately 20 AHI events per hour in the short-term follow-up (<1 year) and approximately 16 AHI events per hour in long-term follow-up.10 These benefits are durable, with sustained efficacy reported five years after implantation.11 Research continues on alternative approaches to expand eligibility (e.g., higher BMI, alternative pathways of airway collapse). Adverse effects are uncommon and may include tongue discomfort, insomnia, frequent awakenings, and local pain triggered by the stimulation impulse. Despite these issues, adherence and patient satisfaction remain high.
Hypoglossal nerve stimulator
Tirzepatide is the first FDA-approved treatment for moderate to severe OSA in adults with obesity, based on evidence showing substantial reductions in AHI and improvements in patient-reported outcomes and cardiometabolic risk factors. Its efficacy is attributed primarily to weight loss. Studies showed a statistically significant reduction in AHI at 29.3 events per hour compared to a reduction of 5.5 events per hour in the placebo group.12 There were reductions in oxygen desaturation, body weight, systolic blood pressure, and patient-reported sleep symptoms. More than 50% of patients reached AHI thresholds where PAP therapy may no longer be indicated. In addition to the above results, a study in Chest assessed obese patients with OSA, with the primary outcome of all-cause mortality and secondary outcomes including major adverse cardiovascular events (MACE) and major adverse kidney events (MAKE). Among the 42,300 studied over a nearly three-year period (January 2022 to November 2024), those treated with tirzepatide had a lower risk of all-cause mortality (HR 0.443) compared to placebo, with reduced risks of MACE (HR 0.731) and MAKE (HR 0.427) across all subgroups (age, sex, BMI, PAP use) except for age 18-39. Authors concluded that “tirzepatide may be a potential therapeutic option for improving clinical outcomes [in obese patients with OSA]”.13 While potentially exciting, critics of the study noted that it included significantly obese subjects (BMI >39) and had extensive exclusion criteria, which may limit generalizability. Long-term studies are needed to confirm durability and safety.14
Glucagon-like peptide-1 agonist
Obstructive sleep apnea (OSA) is a common sleep-related breathing disorder characterized by repeated episodes of partial or complete upper airway obstruction during sleep. Severe, untreated OSA is strongly associated with increased all-cause and cardiovascular mortality. Although observational studies suggest that treatment may reduce these risks, randomized controlled trials have not yet confirmed a definitive mortality benefit. Current therapies focus on maintaining airway patency, improving sleep quality, and mitigating long-term health risks. Emerging treatments, such as tirzepatide, show promise for reducing mortality, but further research is needed. For life and disability insurance underwriting, OSA severity, treatment adherence, and comorbidities should be carefully evaluated. As new therapies and stronger outcome data become available, underwriting guidelines are likely to evolve to reflect the complex relationship between OSA management and long-term risk.
Dr. Jeffrey Henderson, Vice President and Medical Director for US Individual Life, supports RGA clients through medical consultations, expert opinions and via training and education for underwriting, actuarial and claims departments. Jeff is both an experienced clinical practitioner and insurance medical director. He joined RGA in 2025. Prior to RGA, Jeff was a Medical Director for AXA/Equitable. During his clinical practice, he also did part-time disability assessments for Professional Disability Associates. He served as a primary care physician in Delmar, NY and Ludlow, MA prior to transitioning to insurance medicine. Jeff received his Doctor of Osteopathic Medicine from the Kansas City University of Medicine and Biosciences in Kansas City, Missouri. He completed his Internal Medicine residency at Albany Medical College in Albany, NY. Jeff is board-certified in both Insurance Medicine and Internal Medicine. He currently serves as Chair of the Education Committee for the American Academy of Insurance Medicine (AAIM), and is a member of AAIM’s Executive Council. Jeff is a multiple-time member of AAIM’s Scientific Committee. He has also served as a former member of the Association of Home Office Underwriters (AHOU) Program Committee. In 2020, he presented at the Manhattan Underwriter Discussion Group (MUD). Jeff is a member of the American Board of Internal Medicine.
Dr. Jeffrey Henderson
Vice President, Medical Director
Jeffrey.Henderson@rgare.com
What’s New?
Digital twins in healthcare and insurance
Dr. Lauren Acton, MBChb, has joined RGA South Africa as Chief Medical Officer. Lauren completed her medical studies and obtained her Bachelor of Medicine, Bachelor of Surgery degree at the University of Pretoria in South Africa in 2006. After her internship and community service in Johannesburg, she pursued a Master’s degree in bioethics at the University of Stellenbosch, also in South Africa. Her experience encompasses both clinical and insurance medicine, having worked in a private practice as well as for a direct insurer and a reinsurer before coming to RGA.
After a quarter-century with RGA South Africa, Dr. Anthony (Tony) Crosley, the branch’s Chief Medical Officer, is retiring. Tony came to the South Africa office soon after its 1999 launch, and has played a major role in the success and market standing of the underwriting and medical teams. A physician and veteran of more than half-century in insurance medicine, Tony is a doyen of the field: his immense medical and insurance knowledge, work ethic, capabilities, and collegiality are well known, and will be missed. We wish him the very best in his life’s next journey.
Medical Team Updates
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Drug Watch: Additional Copy
Editor's note: These findings emphasize the need for nuanced risk assessments in insurance that consider the duration and timing of metabolic syndrome, leading to more accurate underwriting, better pricing, and targeted wellness programs.
Role of age and exposure duration in the association between metabolic syndrome and risk of incident dementia: a prospective cohort study
Oliver, A.J. et al. Single-cell integration reveals metaplasia in inflammatory gut diseases. Nature 635, 699–707 (2024). https://www.nature.com/articles/s41586-024-07571-1
Mapping 1.6 million gut cells to find new ways to treat disease: Single-cell integration reveals metaplasia in inflammatory gut diseases
Publications relevant to insurance medicine appearing recently in research literature.
Research Watch
Health View I
Industry Event
Drug Watch
RGA Thought Leadership
As the healthcare industry embraces digital transformation, the integration of digital twin technology promises to unlock new avenues for innovation, cost optimization, and enhanced patient outcomes – and new opportunities for life and health insurers.
Read more about this topic on RGA’s Knowledge Center
Editor’s note: GLP-1 agonists could potentially reduce healthcare costs and improve health outcomes associated with AUD and SUD. However, it is important to consider their high cost and the need for more longitudinal data in this context.
Repurposing semaglutide and liraglutide for alcohol use disorder
Editor’s note: Gaining deeper understanding of the inflammation cycle could lead to new ways to prevent or treat inflammatory bowel disease and provide learnings applicable to other conditions. This could improve risk assessments, underwriting, and health outcomes, leading to more personalized and cost-effective insurance coverage.
Qureshi D. et al. The Lancet Healthy Longevity, Volume 5, Issue 12, 100652 https://www.thelancet.com/journals/lanhl/article/PIIS2666-7568(24)00185-5/fulltext
Lähteenvuo M. et al. JAMA Psychiatry. 2025;82(1):94-98. doi:10.1001/jamapsychiatry.2024.3599 https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2825650
In this comprehensive study, researchers integrated over 25 single-cell datasets to create the largest information resource of the human gut, encompassing samples from both healthy and diseased individuals. This Gut Cell Atlas, a significant component of the Human Cell Atlas project, aids in identifying changes associated with conditions such as ulcerative colitis and Crohn’s disease, thereby facilitating the discovery of new drug targets. Additionally, the study revealed that gut metaplastic cells are involved in inflammation. This invaluable resource is freely accessible to researchers worldwide, and its approach can be applied to other organs, significantly advancing our understanding of health and disease.
Read more
This population-based study of over 20,000 individuals aged 50-79 years with 25 years of follow-up found that metabolic syndrome significantly increases the risk of developing dementia. The risk was particularly high for those with metabolic syndrome in mid-life (60-69 years) and for those with prolonged exposure to metabolic syndrome over 20 years. No significant association was found in late-life (70-79 years) or for those with newly developed metabolic syndrome. These findings highlight the importance of both the presence and duration of metabolic syndrome in assessing dementia risk and suggest critical periods for intervention.
In a Swedish nationwide register-based study, glucagon-like peptide-1 (GLP-1) agonists semaglutide and liraglutide were linked to a significantly reduced risk of alcohol use disorder (AUD) and substance use disorder (SUD) hospitalizations, as well as somatic hospitalizations. No significant changes in suicide attempt risk were observed, although semaglutide showed a potential decrease. These GLP-1 agonists performed better than traditional AUD medications (naltrexone, disulfiram, and acamprosate), but comparisons should be interpreted cautiously. The study suggests GLP-1 agonists might help treat various addictions due to their effects on craving and reward pathways. However, as an observational study, it shows only associations, not causality. Randomized clinical trials are needed to confirm these findings.
Health View
Article
Dr. Steve Woh, Medical Director and Health Claims, RGA Global Medical Simon Dreyer, Vice President and Chief Actuary, RGA Global Health Raajeev Bhayana, Head of Health Underwriting, RGA Global Underwriting
Global Health Brief: The rise of GLP-1 receptor agonists and their impact on health insurance
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Colin M. DeForge, Vice President, Underwriting, US Underwriting, US Individual Life Leigh Allen, Associate Vice President, Strategic Research Trey Reynolds, Executive Vice President, Strategy & New Business Development, MIB, Inc.
How Insurers Combat the Complexities and Challenges of Fraud
Hilary Henly, Global Medical Researcher, Strategic Research, RGA
The Cost of Cancer: Price Versus Life
Dr. Adela Osman, Vice President, Head of Global Medical, RGA
For recent ReFlections articles, click here.
Underwriting Update
References: https://www.nature.com/articles/s41746-024-01073-0 https://www.theactuary.com/2024/04/04/power-two-digital-twins-insurance
Dr. Lauren Acton, MBChb
Chief Medical Officer RGA South Africa
Lauren.Acton@rgare.com
Dr. Steve Woh, Medical Director and Health Claims, RGA
A digital twin is a virtual representation constructed from real-time data of a physical entity, continuously updated with ongoing data to simulate and predict its behavior. Conceived in the 1960s, the digital twin concept is now gaining traction in the healthcare industry, offering a wealth of potential applications that could revolutionize patient care and streamline treatment delivery, which affects the insurance sector in many ways. In healthcare, digital twins can simulate patient-specific models, integrating data from medical records, genetic information, and real-time health monitoring devices. This allows for personalized treatment plans, predictive diagnostics, and improved patient outcomes. Furthermore, digital twins can facilitate clinical trials and drug development by providing a safe, controlled environment for experimentation. Together, these advances could potentially lead to more accurate predictive analytics and sharper risk stratification, allowing insurers to tailor coverage and pricing based on individual health profiles rather than demographic details. By creating detailed simulations of policyholders, digital twins can improve risk assessment and healthcare cost prediction, which leads to more accurate underwriting and policy pricing. Additionally, digital twins enable continuous monitoring of policyholders’ health, allowing insurers to offer dynamic and effective insurance models. This proactive approach can help promote a longer lifespan and a more robust “healthspan,” as well as facilitate early detection of health issues, potentially reducing the frequency and severity of claims.
Health View II
References: https://www.dw.com/en/how-australias-social-media-ban-could-affect-us/video-70972818 https://oxford.shorthandstories.com/social-media-digital-mental-health/index.html https://theconversation.com/australias-social-media-ban-for-kids-under-16-just-became-law-how-it-will-work-remains-a-mystery-244736 https://theconversation.com/the-government-has-introduced-laws-for-its-social-media-ban-but-key-details-are-still-missing-244272
To address these issues, authorities are studying ways to protect vulnerable people. In Australia, for example, a controversial law to ban social media use for children under 16 was introduced in November 2024. There remain more questions than answers as to whether the law will be effective in mitigating negative outcomes. As the digital age continues its rapid evolution, it is crucial to strike a balance between leveraging technology’s potential benefits and mitigating its negative impacts on mental health. A nuanced approach incorporating education, regulation, and the development of healthy digital habits is essential for promoting overall wellbeing.
The digital age has profoundly impacted mental health, producing both promising advances and significant challenges. On one hand, technology has democratized access to mental health resources and support networks. Online communities and forums provide platforms for individuals to share experiences and seek support, fostering a sense of belonging and reducing feelings of isolation. Additionally, mental health wellness apps and emerging digital therapeutics have made interventions more accessible, allowing users to manage stress, anxiety, and depression conveniently. In the UK, the National Institute for Health and Care Excellence (NICE) recommended digital tools to help children and young people with anxiety, some of which were adopted by the National Health Service (NHS). On the other hand, the digital age has introduced new stressors and challenges. Social media, while connecting people, often promotes a culture of comparison, leading to feelings of inadequacy and negatively impacting self-esteem for some people. The constant connectivity and bombardment of information can also contribute to feelings of anxiety and overwhelm. Social media use has been linked to increased rates of digital burnout and depression, particularly among young adults. Additionally, cyberbullying and online harassment bring potentially severe psychological consequences. One study found significant potential for harm from online behavior, particularly noting high levels of internet use and internet addiction and websites with self-harm or suicide-related content.
Mental health in the digital age
Dr. Anthony Crosley
Dr. Anthony (Tony) Crosley
acrosley@rgare.com
Dr. Lauren Acton
Kaitlyn Fleigle, Actuary, Strategic Research, Global Actuarial Pricing and Research Hilary Henly, Global Medical Researcher, Strategic Research
A Post-Pandemic View of Alcohol Consumption
Dr. Peter Farvolden, Mental Health Consultant Dr. Adela Osman, Vice President, Head of Global Medical
Psychological Resilience: Health impacts and implications for insurers
Casey Wang, Senior Assistant Actuary, Strategic Underwriting Initiatives Guizhou Hu, Vice President, Head of Risk Analytics, Global Underwriting, Claims, and Medical, RGA
RGA Study: The connection between mental health disorders and all-cause mortality
ICLAM 2025 The International Committee for Insurance Medicine (ICLAM) will host the ICLAM 2025 Conference May 11-14, 2025 in Estoril, Portugal. This four-day conference, a leading industry event, will welcome expert speakers from around the world and draw a global audience. Information and registration can be found at www.iclam2025.org.
Industry Event:
Craig Armstrong, Vice President, Senior Actuary, and Data Scientist, Global Research and Development Chris Falkous, Vice President, Senior Biometric Insights Actuary, Global Research and Development Richard Russell, Vice President, Biometric Research, Global Research and Development Andrew Gaskell, Vice President and Senior Actuary, Enterprise Pricing Ben Johnson, Vice President and Managing Actuary, Global Valuation Elena Tonkovski, Vice President and Senior Actuary, Insurance Risk, Global Risk Services
Evaluating Biometric Trend Drivers
Kaitlyn Fleigle, Actuary, Strategic Research, Innovation & Content Hilary Henly, Global Medical Researcher, Strategic Research Sara Goldberg, Vice President and Actuary, Pricing Dan Brandt, Vice President & Actuary, Experience Studies & Analytics, US Individual Life Julianne Callaway, Vice President and Senior Actuary, Strategic Research, Global Actuarial Pricing and Research
A Turning Tide? How Insurers Can Navigate an Evolving Substance Use Crisis
Jeff Heaton, Vice President, AI Innovation Michael Hill, Vice President, Fac Underwriting Strategy and Data Analytics
AI Upskilling in Insurance: Boosting careers and building business
Dr. John J. Lefebre, Vice President and Senior Technical Global Medical Director, Global Medical
Reframing Obesity as a Treatable Condition
Video
Jacqueline Waas, Vice President, Underwriting Research and Development, US Individual Life
Inside Your Digital Underwriting Evidence Toolbox
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Editor’s note: Emerging research shows COVID-19 mRNA vaccines may enhance cancer immunotherapy outcomes by priming immune responses – an insight that could reshape life insurance risk models for immunotherapy patients. As survival rates improve, insurers may need to reassess underwriting criteria and long-term projections.
A.J. Grippin et al., SARS-CoV-2 mRNA vaccines sensitize tumors to immune checkpoint blockade. Nature (2025). https://doi.org/10.1038/s41586-025-09655-y
SARS-CoV-2 mRNA vaccines sensitize tumors to immune checkpoint blockade
Editor's note: These results raise important considerations for life insurance underwriting. As cannabis becomes more mainstream, insurers may need to factor its metabolic impact into risk assessments and policy design.
European Association for the Study of Diabetes. Cannabis use may quadruple diabetes risk.” ScienceDaily. ScienceDaily, 14 September 2025. www.sciencedaily.com/releases/2025/09/250914205803.htm
Cannabis use may quadruple diabetes risk
Ana Villaplana-Velasco et al., Mendelian randomization study implicates inflammaging biomarkers in retinal vasculature, cardiovascular diseases, and longevity. Sci. Adv.11,eadu1985(2025). DOI:10.1126/sciadv.adu1985 https://doi.org/10.1126/sciadv.adu1985
Editor’s note: Retinal scans are emerging as a powerful, non-invasive tool for assessing cardiovascular risk and biological aging – two key factors in life insurance underwriting. These findings could reshape how insurers evaluate longevity and health, paving the way for faster, more predictive risk models.
Aging in plain sight: What new research says the eyes reveal about aging and cardiovascular risk
A comprehensive study from MD Anderson Cancer Center reveals that COVID-19 mRNA vaccines can significantly enhance the effectiveness of immune checkpoint inhibitors (ICIs) in treating cancers like non-small cell lung cancer (NSCLC) and melanoma. Patients who received a COVID-19 mRNA vaccine within 100 days of starting ICI therapy showed markedly improved overall and progression-free survival. The vaccine triggers a surge in type I interferon, activating antigen-presenting cells and priming T cells to attack tumors. This immune activation also increases PD-L1 expression on tumors, making them more responsive to ICIs – even in immunologically “cold” tumors. Preclinical models confirmed these effects, showing that RNA-lipid nanoparticles (RNA-LNPs) stimulate both innate and adaptive immunity, leading to tumor regression. The findings suggest that widely available mRNA vaccines, even those targeting non-cancer antigens like SARS-CoV-2, could serve as powerful adjuncts to immunotherapy, potentially transforming treatment strategies and expanding access to effective cancer care.
A large-scale study involving over 4 million adults has found that cannabis users are nearly four times more likely to develop diabetes compared to non-users. Presented at the European Association for the Study of Diabetes (EASD) annual meeting, the research analyzed health records from multiple international cohorts and controlled for various lifestyle and health factors. The findings suggest a strong association between cannabis use and increased diabetes risk, potentially linked to insulin resistance and poor dietary habits. As cannabis becomes more widely accepted and legalized, experts emphasize the need for greater awareness of its metabolic risks and recommend integrating diabetes screening into substance use counseling. However, the study’s retrospective design and limitations in cannabis exposure data mean further research is needed to confirm causality and explore long-term effects.
Researchers from McMaster University and the Population Health Research Institute have discovered that tiny blood vessels in the eye may help predict heart disease risk and biological aging. Their study, published in Science Advances on October 24, 2025, shows that retinal scans – combined with genetic and blood biomarker data – can reveal vascular health and aging patterns. Analyzing data from over 74,000 participants across four major cohorts, they found that simpler, less-branched retinal vessels were linked to higher cardiovascular risk and signs of aging, such as inflammation and reduced lifespan. The research also identified proteins like MMP12 and IgG–Fc receptor IIb as potential drug targets to slow vascular aging and improve longevity, suggesting retinal scans could become a quick, non-invasive tool for early detection and intervention.
Dr. Adela Osman Senior Vice President, Head of Global Medical
Futile organ procurement remains a costly and persistent challenge in liver transplantation. In donation after circulatory death (DCD) cases, surgical teams often prepare for organ recovery only to abandon the procedure because the donor does not die within the required timeframe. These failed attempts consume ICU resources, operating room time, and staff effort, driving up healthcare costs that ultimately impact insurers through higher claims and prolonged hospital stays. A recent multicenter study published in The Lancet highlights a promising solution: a machine-learning model built on the light gradient boosting machine (LightGBM) framework. By analyzing complex physiological, cardiovascular, and neurological data, the model predicts, with remarkable accuracy, whether a donor will progress to death within the necessary window. Validated across six US transplant centers, the tool reduced futile procurements by up to 60%, outperforming traditional calculators and even surgeon judgment. This breakthrough represents more than a clinical win. By minimizing wasted interventions, hospitals can redirect resources to cases with higher success potential, reducing unnecessary costs and improving overall system efficiency and performance. For health insurers, this directly translates into fewer claims tied to failed transplant attempts. Additionally, better donor management accelerates successful transplants, improving survival rates for patients on waiting lists, potentially delaying death benefit payouts. These factors may influence underwriting and pricing for critical illness, transplant-related coverage, and even life policies. Although the LightGBM model is still evolving, AI-driven decision tools like this are poised to reshape healthcare economics. Insurers who adapt their risk models to reflect these efficiencies will be better positioned in a market increasingly defined by precision and resource optimization. Development and validation of a machine-learning model to reduce futile procurements in donations after circulatory death in liver transplantation in the USA: a multicentre study – The Lancet Digital Health
AI Cuts Waste in Organ Donation
Dr. Steve Woh Vice President, Global Medical Director
Health View:
Antimicrobial resistance (AMR) is rapidly escalating into a global health crisis. According to the World Health Organization (WHO), one in six bacterial infections now resists antibiotics, and annual AMR-related deaths could rise by 74.5%, reaching 8.22 million by 2050. This trend threatens to increase hospital stays, add to treatment complexity, and affect mortality – factors that directly impact life and health insurance costs. In response, GlaxoSmithKline (GSK) and the Fleming Initiative have launched major research programs covering six themes by leveraging advanced artificial intelligence (AI) to accelerate solutions. Dubbed “Grand Challenges,” these initiatives seek to: Discover new antibiotics for resistant Gram-negative bacteria, which are among the hardest to treat. Develop therapies for resistant fungal infections such as Aspergillus. Model immune responses to pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) to inform vaccine development. Use AI-driven surveillance to predict resistance patterns. Optimize antibiotic use. Apply data and insights to inform policies, engage the public, and support coordinated action. By combining supercomputing power with molecular data, these initiatives seek to break through long-standing scientific barriers and make critical datasets globally accessible, potentially transforming infection prevention and treatment strategies. For insurers, AMR drives higher claims through prolonged ICU stays, costly therapies, and increased mortality risk. Left unchecked, it could significantly raise premiums for life insurance benefits and health coverage payouts. AI-enabled breakthroughs offer the potential to curb these trends by reducing treatment failures, improving patient survival, and shortening hospitalizations – all of which directly benefit health insurers. Insurers should also revisit underwriting assumptions and pricing for health, critical illness, and even life coverage as predictive modelling and precision medicine reshape risk profiles. As AMR research accelerates, insurers that anticipate these shifts will be better positioned to manage emerging risks and align products with evolving healthcare standards. GSK and Fleming Initiative scientists unite to target AMR with advanced AI | GSK
AI Versus Superbug
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Frailty: The silent challenge of aging
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In hac habitasse platea dictumst
video
A Turning Tide on Substance-Related Mortality?
Proper Pairing Maximizes Effectiveness of Digital Underwriting Evidence
Please click the articles below to see some of RGA's recently published thought leadership on underwriting topics.
The development of RGA’s underwriting philosophy demands strong research skills and a deep understanding of risk, as well as appreciation for the need to apply this expertise in practical situations. RGA’s Global Underwriting Philosophy and Education team is dedicated to providing clients with new resources, up-to-date guidelines, and detailed information about the many risk factors and related considerations underwriters may face.
Knowledge sharing In alignment with the Global Underwriting Manual (GUM) recent update to our feeding and eating guidelines, Akhilesh Pandey published a Knowledge Center article entitled, “Eating Disorders: Solving complexities for underwriting and claims.” It addresses the risk assessment challenges insurers face due to the complexities of these conditions. Following our update on frailty, Reema Nathwani Jani published an article on the topic, entitled “Frailty: The silent challenge of aging.” Discover GUM’s interactive banner! We are excited to unveil a dynamic new way to access RGA’s expanding suite of resources and learning materials. Launched in October 2025, our clients can now explore resource hubs, Learning Gateway courses, and informative “What’s New” one-pagers directly from the GUM homepage – just click the interactive banner for instant access. Watch the feature introduction video to unlock the full potential of this innovative tool. Extensive topic updates Major revisions: hallucinogens, leukopenia and neutropenia, and frailty Minor updates: Gastritis with H. pylori positive, intestinal metaplasia, vitamin D deficiency, family history of nasopharyngeal cancer, ADHD, myocardial bridging, non-alcoholic fatty liver disease, lung neuroendocrine tumors, bundle branch block, hypercholesterolemia, and carotid artery disease Health topics: Aortic regurgitation and aortic stenosis
New resource hubs In Q3 2025, we enhanced the Mental Health Resource Hub by updating guidelines for autism spectrum disorder, feeding and eating disorders, and bipolar disorder. Additionally, new e-learning modules covering mood disorders, stress and anxiety disorders, and mental health concepts were added to Learning Gateway.
Explore the Alcohol Consumption Resource Hub
An underwriting manual you can count on GUM by the numbers 2024: 695,000+ logins 1.3 million+ calculations 800,000+ Precision Calculator uses 3.2 million+ topic views
We look forward to providing you with news and updates regarding the Global Underwriting Manual in future issues of ReFlections. *GUM guidelines in North America can vary from those applied across all other markets. RGA clients in US and Canada, please click here to access your customized GUM resources.
By Brooke Butler, Director, Marketing and Communications – Global Underwriting Philosophy
Case ReView
Dr. Sheetal Salgaonkar, MBBS, MD, DBIM, FALU
Vice President and Global Medical Director
Unpacking Neuroendocrine Tumors in Critical Illness
Case summary: A 44-year-old woman was issued a $50,000 critical illness policy at standard rates in 2022. Two years later, she presented with recurrent right lower abdominal pain. A clinical examination revealed localized tenderness without signs of peritonitis. The initial sonographic evaluation was unremarkable, and laboratory investigations were within normal limits. The patient was admitted for further assessment and subsequently underwent a laparoscopic appendectomy. Intraoperative findings demonstrated a phlegmonous appendix with a distended tip, without evidence of perforation. Below is the histology report: The appendix vermiformis showed an obliterated tip with connective tissue infiltrated by a well-differentiated, tubular neuroendocrine tumor measuring approximately 1.1 cm. Mitotic activity was low, with fewer than 2 mitoses per square millimeter. The tumor extended up to 0.1 cm into the subserosa/mesoappendix. MIB-1 staining indicated a proliferation index of less than 1%. Immunohistochemistry confirmed tumor cells were positive for synaptophysin, chromogranin, and AE1/AE3 – consistent with neuroendocrine differentiation.
Diagnosis: Neuroendocrine tumor of the appendix. A claim was submitted under the cancer category, based on the following critical illness (CI) definition. Critical illness definition of cancer as per policy wording: Cancer is a malignant tumor characterized by uncontrolled growth and invasion of other tissue. This includes leukemia, lymphoma, and Hodgkin’s disease. A benign tumor is not a cancer. Diagnosis must be confirmed by a pathology report from a specialist. Excluded are precancerous tumors. These include premalignant and borderline malignant tumors as well as carcinoma in situ. In the case of cancer originating in the bone marrow (e.g., leukemia), we cover only if it has caused anemia or affected more than one lymph node region. For skin cancer, we will pay only if it is a malignant melanoma with a penetration depth of more than 2 mm. Questions Q1. What are neuroendocrine tumors? Neuroendocrine tumors (NETs), formerly referred to as carcinoid tumors, are rare epithelial neoplasms that can develop in various parts of the body. These slow-growing tumors originate from neuroendocrine cells and have the ability to secrete a range of peptides and neuroamines. The annual incidence of NETs is estimated at approximately 2.5 to 5 cases per 100,000 individuals, with the highest incidence in those between the ages of 50 and 70 years. In adults, NETs are most often found in the gastrointestinal (GI) tract (about 55%), followed by the respiratory tract (30%) and other organs (15%), such as the kidneys or ovaries. In the GI tract, the most common location is the small intestine (45%), followed by the rectum (20%), caecum (16%), colon (11%), and stomach (7%). Q2. How are neuroendocrine neoplasms graded and staged? Neuroendocrine neoplasms (NENs) are classified under two main subtypes: neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs), distinguished by their level of differentiation and growth rate. NETs are well-differentiated and typically slow growing, while NECs are poorly differentiated, high-grade carcinomas with aggressive behavior. NETs are graded as G1, G2, or G3 based on proliferative activity, which is assessed using the mitotic count and/or Ki-67 proliferation index. NET staging uses the TNM system (AJCC/ENETS), which classifies disease from stage I to stage IV based on how large and invasive the primary tumor is (T), whether regional lymph nodes contain cancer (N), and whether there are distant metastases (M), with organ specific rules for gastro entero pancreatic and other NET sites. The International Classification of Diseases for Oncology (ICD-O) coding for NETs changed in September 2011 (and came into force January 1, 2012). Prior to this date, they were given a behavior code of /1 , which meant “borderline,” but now all NETs have a behavior code /3, meaning they are now regarded as malignant. Q3. Does this case meet the criteria outlined in the CI definition? Yes. The 1.1 cm well-differentiated NET infiltrated the subserosa, which classifies it as a T3 tumor. None of the exclusions apply, and the case meets the policy definition of cancer as outlined above. Under ICD-O, all NETs are now coded as /3 (malignant), which means they may qualify for cancer payouts under critical illness benefits, therefore requiring appropriate pricing. As an alternative approach, insurers could consider adding an exclusion for small, low-grade NETs within the CI cancer definition, given their generally favorable prognosis. Q4. Which key factors should be considered when underwriting neuroendocrine tumors? NETs can develop in almost all organs of the body. Underwriting NETs requires assessment of the primary site, as prognosis varies significantly. The prognosis of appendiceal NETs is excellent, with more than 90% survival probability at 10 years and an overall risk of metastases of <10%, whereas stomach or gastric NETs have a 5-year overall survival of 81.1% for all stages combined. Pancreatic NETs have a worse 5-year survival of about 53% for all stages combined. Tumor grade and differentiation are critical, with well-differentiated (G1/G2/G3) tumors having a better prognosis than poorly differentiated (NEC) types. Stage and extent of disease – including tumor size, depth of invasion, and presence of nodal or distant metastases – directly impact risk. Additional factors include mitotic rate, Ki-67 proliferation index, lymphovascular or perineural invasion, and completeness of surgical resection. NET guidelines have been recently published in GUM. These research-based, simplified guidelines have expanded rating tables for risk assessment across all benefits for site-specific NETs. Key takeaways: NETs are well differentiated, usually slower growing tumors, whereas NECs are poorly differentiated, high grade carcinomas that behave much more aggressively. All NETs are now coded as malignant (/3) according to ICD-O, which means they can be considered for cancer payouts under critical illness (CI) definitions unless specifically excluded. The prognosis of NETs depends on several factors, including the primary site, grade, stage, extent of disease, and completeness of surgical resection.
Please click the articles below to see some of RGA's published thought leadership on claims topics.
Claims Updates
Excellence in claims management demands deep technical expertise and a human touch. To support this, RGA delivers high-quality training and continuing education through our Pathfinder claims training program, available exclusively to RGA clients via the Global Claims Manual/Guide.
Expanding Mental Health Resources Managing mental health claims remains a key focus. Last year RGA launched the Claims Mental Health Toolkit, giving clients practical tools and guidance to manage these claims confidently and compassionately. Earlier this year we added a new Pathfinder module to the Toolkit: Essential Mental Health Literacy for Claims Assessors. This module delves into various aspects of mental health literacy, including stigma and bias, empathetic communication strategies, and guidance for interpreting clinical terminology.
We continue to expand our support for claims professionals managing mental health claims and have now introduced a new Pathfinder training series: Understanding Delayed Recovery in Mental Health. This program tackles one of the biggest challenges in disability income claims – prolonged recovery timelines. The series consists of six interactive modules, split into two parts: Core Concepts – foundational knowledge and context Deepening Your Understanding – practical strategies for managing complex cases The modules help assessors overcome treatment barriers, apply proactive interventions, and move claims from stagnation to active, progressive management.
Get Started’ Training RGA’s “Get Started” modules provide comprehensive, self-paced learning for benefits, including Death, Critical Illness, Total and Permanent Disability, and Health. Designed for busy claims professionals, these modules are intentionally short, snappy, and engaging – crafted to deliver practical insights in a concise format that respects the demands of the claims professional’s workload. Each module features interactive elements, real-life examples, and multimedia content.
Explore Pathfinder. Click here for an overview of modules by benefit type and experience level.
By Jennie Calder Brown, Executive Director, Global Claims Philosophy and Education Gayle Kanchanapume, Executive Director, Global Claims Philosophy and Education
Coming soon “Get Started” training for Disability Income claims. Innovation and Continuous Improvement We remain committed to delivering training, thought leadership, and tools that empower claims professionals worldwide. For more information or to access these resources, visit the Global Claims Manual/Guide or contact the Global Claims team.
Delayed Recovery in Mental Health Claims: Rethinking the role of secondary gain
Navigating the Complexities of Personality in Mental Health Claims
Effective Disability Claims: A partnership case study
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The Longer Life Foundation (LLF) is a collaboration of more than a quarter century between RGA and Washington University School of Medicine in St. Louis. We are pleased to bring you our January 2026 newsletter, which discusses the foundation’s many recent activities. To find out more about LLF and the research it has funded to date, please visit www.longerlife.org or reach out to Dr. Preeti Dalawari at preeti.dalawari@rgare.com or Dr. Joesph Zhang at wzhang@rgare.com.
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