A Summary from the Institute for Clinical and Economic Review's New England Comparative Effectiveness Public Advisory Council.

DISCLOSURES: Funding for this summary was contributed by the Laura and John Arnold Foundation, Blue Shield of California, and California Health Care Foundation to the Institute for Clinical and Economic Review (ICER), an independent organization that evaluates the evidence on the value of health care interventions. ICER's annual policy summit is supported by dues from Aetna, AHIP Anthem, Blue Shield of California, CVS Caremark, Express Scripts, Harvard Pilgrim Health Care, Cambia Health Solutions, United Healthcare, Kaiser Permanente, Premera Blue Cross, AstraZeneca, Genentech, GlaxoSmithKline, Johnson & Johnson, Merck, National Pharmaceutical Council, Prime Therapeutics, Sanofi, Spark Therapeutics, Health Care Service Corporation, Editas, Alnylam, Regeneron, Mallinkrodt, Biogen, HealthPartners, and Novartis. Otuonye, Kumar, and Pearson are ICER employees. Banken received consulting fees from ICER for work on this report.

Impact of Abuse Deterrent Formulations of Opioids in Patients With Chronic Pain in the United States: A Cost-Effectiveness Model.

OBJECTIVE: Opioid abuse is a significant public health problem in the United States. We evaluate the clinical effectiveness and economic impact of abuse-deterrent formulations (ADF) of opioids relative to non-ADF opioids in preventing abuse. METHODS: We developed a cost-effectiveness model simulating 2 cohorts of 100 000 noncancer, chronic-pain patients newly prescribed either ADF or non-ADF extended-release (ER) opioids and followed them over 5 years, tracking new events of opioid abuse and opioid-related overdose deaths in addition to tracking 5-year cumulative costs of therapeutic use and abuse of ADF and non-ADF opioids. Patients in each cohort entered the model for therapeutic opioid use from where they could continue in that pathway, discontinue opioid use, or abuse opioids or die of opioid overdose-related or unrelated causes. In addition, one-way sensitivity and scenario analysis were conducted. RESULTS: Over a 5-year time period, using ADF opioids prevented an additional 2300 new cases of opioid abuse at an additional cost of approximately $535 million to the healthcare sector. Threshold analyses showed that a 40% decrease in ADF opioid costs was required to attain cost neutrality between the 2 cohorts, whereas a 100% effectiveness in abuse reduction still did not result in cost neutrality. A 43% decrease in diversion with ADFs relative to non-ADFs was required to attain cost neutrality. Including a societal perspective produced results directionally similar to the base-case analysis findings. CONCLUSION: ADF opioids have the potential to prevent new cases of opioid abuse, but at substantially higher costs to the health system.

Cost Utility of Voretigene Neparvovec for Biallelic RPE65-Mediated Inherited Retinal Disease.

OBJECTIVE: The gene therapy voretigene neparvovec (VN) is the first Food and Drug Administration-approved treatment for vision loss owing to the ultra-rare RPE65-mediated inherited retinal disorders. We modeled the cost-utility of VN compared with standard of care (SoC). STUDY DESIGN: A 2-state Markov model, alive and dead, with a lifetime horizon. METHODS: Visual acuity (VA) and visual field (VF) were tracked to model quality-adjusted life-years (QALYs). VN led to an improvement in VA and VF that we assumed was maintained for 10 years followed by a 10-year waning period. The cost of VN was $850 000, and other direct medical costs for depression and trauma were included for a US healthcare system perspective. A modified societal perspective also included direct nonmedical costs and indirect costs. RESULTS: VN provided an additional 1.3 QALYs over the remaining lifetime of an individual. The average total lifetime direct medical cost for individuals treated with VN was $1 039 000 compared with $213 400 for SoC, leading to an incremental cost-effectiveness ratio (ICER) of $643 800/QALY from the US healthcare system perspective. Direct nonmedical costs totalled $1 070 900 for VN and $1 203 300 for SoC, and indirect costs totalled $405 400 for VN and $482 900 for SoC, leading to an ICER of $480 100/QALY from the modified societal perspective. CONCLUSIONS: At the current price, VN was unlikely to reach traditional cost-effectiveness standards compared with SoC. VN has important implications for both development and pricing of future gene therapies; therefore clinical and economic analyses must be carefully considered.

Long-term clinical impact and cost-effectiveness of obeticholic acid for the treatment of primary biliary cholangitis.

Primary biliary cholangitis (PBC) is a chronic, progressive autoimmune liver disease that mainly affects middle-aged women. Obeticholic acid (OCA), which was recently approved by the Food and Drug Administration for PBC treatment, has demonstrated positive effects on biochemical markers of liver function. Our objective was to evaluate the long-term clinical impact and cost-effectiveness of OCA as a second-line treatment for PBC in combination with ursodeoxycholic acid (UDCA) in adults with an inadequate response to UDCA. We developed a mathematical model to simulate the lifetime course of PBC patients treated with OCA+UDCA versus UDCA alone. Efficacy data were derived from the phase 3 PBC OCA International Study of Efficacy trial, and the natural history of PBC was informed by published clinical studies. Model outcomes were validated using the PBC Global Study. We found that in comparison with UDCA, OCA+UDCA could decrease the 15-year cumulative incidences of decompensated cirrhosis from 12.2% to 4.5%, hepatocellular carcinoma from 9.1% to 4.0%, liver transplants from 4.5% to 1.2%, and liver-related deaths from 16.2% to 5.7% and increase 15-year transplant-free survival from 61.1% to 72.9%. The lifetime cost of PBC treatment would increase from $63,000 to $902,000 (1,330% increment). The discounted quality-adjusted life years with UDCA and OCA+UDCA were 10.74 and 11.78, respectively, and the corresponding costs were $142,300 and $633,900, resulting in an incremental cost-effectiveness ratio of $473,400/quality-adjusted life year gained. The results were most sensitive to the cost of OCA. CONCLUSION: OCA is a promising new therapy to substantially improve the long-term outcomes of PBC patients, but at its current annual price of $69,350, it is not cost-effective using a willingness-to-pay threshold of $100,000/quality-adjusted life year; pricing below $18,450/year is needed to make OCA cost-effective. (Hepatology 2017;65:920-928).

Introducing new technology safely.

AIM: This report considers the introduction of new technology and the implications for patient safety. METHODS AND DISCUSSION: A distinction is made between 'conceptually' new and 'contextually' new technology. The life cycle of technology from development to routine use is discussed and the key role for regulation, health technology assessment, clinical engineering and surveillance in this life cycle considered. The limitations of each of these disciplines are also discussed. Special consideration is given to the needs of developing countries. Case study examples of particular challenges in the safe introduction of technology are presented.