Currently Viewing:
The American Journal of Managed Care December 2018
Feasibility of Expanded Emergency Department Screening for Behavioral Health Problems
Mamata Kene, MD, MPH; Christopher Miller Rosales, MS; Sabrina Wood, MS; Adina S. Rauchwerger, MPH; David R. Vinson, MD; and Stacy A. Sterling, DrPH, MSW
From the Editorial Board: Jonas de Souza, MD, MBA
Jonas de Souza, MD, MBA
Risk Adjusting Medicare Advantage Star Ratings for Socioeconomic Status
Margaret E. O’Kane, MHA, President, National Committee for Quality Assurance
Reducing Disparities Requires Multiple Strategies
Melony E. Sorbero, PhD, MS, MPH; Susan M. Paddock, PhD; and Cheryl L. Damberg, PhD
Cost Variation and Savings Opportunities in the Oncology Care Model
James Baumgardner, PhD; Ahva Shahabi, PhD; Christopher Zacker, RPh, PhD; and Darius Lakdawalla, PhD
Patient Attribution: Why the Method Matters
Rozalina G. McCoy, MD, MS; Kari S. Bunkers, MD; Priya Ramar, MPH; Sarah K. Meier, PhD; Lorelle L. Benetti, BA; Robert E. Nesse, MD; and James M. Naessens, ScD, MPH
Patient Experience During a Large Primary Care Practice Transformation Initiative
Kaylyn E. Swankoski, MA; Deborah N. Peikes, PhD, MPA; Nikkilyn Morrison, MPPA; John J. Holland, BS; Nancy Duda, PhD; Nancy A. Clusen, MS; Timothy J. Day, MSPH; and Randall S. Brown, PhD
Relationships Between Provider-Led Health Plans and Quality, Utilization, and Satisfaction
Natasha Parekh, MD, MS; Inmaculada Hernandez, PharmD, PhD; Thomas R. Radomski, MD, MS; and William H. Shrank, MD, MSHS
Primary Care Burnout and Populist Discontent
James O. Breen, MD
Adalimumab Persistence for Inflammatory Bowel Disease in Veteran and Insured Cohorts
Shail M. Govani, MD, MSc; Rachel Lipson, MSc; Mohamed Noureldin, MBBS, MSc; Wyndy Wiitala, PhD; Peter D.R. Higgins, MD, PhD, MSc; Sameer D. Saini, MD, MSc; Jacqueline A. Pugh, MD; Dawn I. Velligan, PhD; Ryan W. Stidham, MD, MSc; and Akbar K. Waljee, MD, MSc
Currently Reading
The Value of Novel Immuno-Oncology Treatments
John A. Romley, PhD; Andrew Delgado, PharmD; Jinjoo Shim, MS; and Katharine Batt, MD
Provider-Owned Insurers in the Individual Market
David H. Howard, PhD; Brad Herring, PhD; John Graves, PhD; and Erin Trish, PhD
Mixed Messages to Consumers From Medicare: Hospital Compare Grades Versus Value-Based Payment Penalty
Jennifer Meddings, MD, MSc; Shawna N. Smith, PhD; Timothy P. Hofer, MD, MSc; Mary A.M. Rogers, PhD, MS; Laura Petersen, MHSA; and Laurence F. McMahon Jr, MD, MPH

The Value of Novel Immuno-Oncology Treatments

John A. Romley, PhD; Andrew Delgado, PharmD; Jinjoo Shim, MS; and Katharine Batt, MD
This study assesses the value of novel immuno-oncology treatments to society.
Survival Gains From I-O Treatment

For each case study, we compared expected survival with the select I-O treatment with survival with an existing standard of care (glycoprotein 100 [gp100] for advanced unresectable melanoma and docetaxel for advanced previously treated squamous NSCLC) using published studies with the longest available follow-up of these patients.7,15-17 Survival curves from these studies were extracted using graph-reading software.

It is also relevant to incorporate survival beyond the end of follow-up. For melanoma, follow-up with ipilimumab is approximately 10 years (with somewhat less than 20% of patients still alive); with gp100, follow-up is approximately 4 years (with approximately 5% of patients still alive). With ipilimumab, the eAppendix (available at shows that mortality becomes rare among patients who survive 36 months. We estimated the survival gain from ipilimumab by assuming that any patient alive at the end of follow-up was cured of cancer. This approach understates the survival gains from ipilimumab insofar as gp100 is less curative than ipilimumab, as noted above. To provide some perspective, we quantified survival gains through 44 months, when follow-up for gp100 ended.15

Under our approach, a cured patient survives according to rates of all-cause mortality from recent US life tables.18 These mortality rates are age specific, so we assumed that patients were diagnosed at the mean/median age for each cancer in the key studies.16,17 In sensitivity analysis, we used the average age at diagnosis reported in the Surveillance, Epidemiology, and End Results (SEER) registry from 2008 to 2012.19 (Details on cohort identification are provided in the eAppendix.) In addition, we addressed heterogeneity in age at diagnosis by calculating average survival gains among those diagnosed younger than average and those diagnosed older than average in the SEER data.

For advanced previously treated squamous NSCLC, follow-up of nivolumab in current literature extends to 66 months.15 As with ipilimumab for melanoma, mortality becomes rare among patients who survive 36 months. We therefore assumed that patients with NSCLC using nivolumab who are still alive at the end of follow-up are cured. For docetaxel, follow-up is just 24 months.16 We addressed this issue in 3 main ways. First, we estimated survival gains from docetaxel through 24 months. Next, we estimated alternative survival functions using available data with the longest follow-up and projected long-term survival (details are presented in the eAppendix). We also considered a scenario in which some patients did not respond differently to nivolumab. Third, we considered a scenario in which some patients experienced durable survival. In this durable survival scenario, we started with the head-to-head survival data.16,17 Beginning at 24 months for both treatments, we applied mortality hazard rates from the survival analyses. Then, at 36 months, we assumed that all patients alive were cured and survived according to all-cause mortality rates. We also considered a scenario in which half of the patients were cured and the other half survived according to the estimated hazard rates.

Each year of survival was discounted at a rate of 3%, consistent with the recommendation of the US Public Health Service’s Panel on Cost-Effectiveness in Health and Medicine.20 Finally, life expectancies in trials were translated into real-world survival using a recent comparison of mean survival in trials and observational studies (specifically, mean survival in the real world was found to be 95% of the survival seen in trials).21

Value of Survival Gains

To determine the value of improved survival to a patient, we applied an economic model developed for application to discrete changes in life expectancy, which has been previously applied in the health context to antiretroviral therapy for HIV/AIDS and tamoxifen for breast cancer.22-24 This model is calibrated to standard parameters, such as risk aversion and willingness to substitute consumption across time periods (details are provided in the eAppendix).

A key input into the model is “full income” as a measure of economic resources, as it is distinct from actual income. Full income represents the full range of economic possibilities and exceeds actual income, which ignores the value of household production, nontraded goods, and leisure. Notably, leisure is “purchased” by working fewer hours and receiving a lower actual income.25 Allowing for 8 hours of sleep per night, total hours exceed full-time work by a factor of 2.8, and average actual family income annually among patients with cancer exceeded $70,000 in the Medical Expenditure Panel Survey during the 2010 to 2013 period.26 In our survival valuation model, we focused on a full income of $200,000, but we also considered the sensitivity of the value estimates to full incomes of $100,000 and $300,000. A prominent analysis of the US context estimated full income within this range for individuals of the average ages at melanoma and NSCLC diagnosis in key studies.16,17

To determine the value of improved survival to society, we aggregated the estimated value to a patient across the number of patients treated in each cohort. We considered value over a window of 5 years of incident cases, because the I-O paradigm is evolving rapidly and may render the treatments considered in our case studies less relevant in the near future. We started by determining the number of patients diagnosed based on primary site, histology, American Joint Committee on Cancer staging, and surgical treatment in the most recent SEER data (2008-2012),19 and we used the SEER coverage rate (28% of the US population in 2010) to produce a national estimate of the size of each cohort of patients diagnosed at an advanced stage. Where relevant data were missing, we conservatively excluded potential cases (detailed in the eAppendix).

In the past, patients with advanced NSCLC have frequently foregone treatment, and so we applied the historical rate of second-line treatment among patients with advanced squamous NSCLC from the literature (16%).27 However, the availability of more efficacious and/or better-tolerated treatment could encourage higher utilization, so a sensitivity analysis considered a scenario in which the treatment rate increased by one-fourth. For advanced melanoma, nontreatment is minimal. However, in sensitivity analyses (detailed in the eAppendix), we addressed the approval of BRAF inhibitors in 2013 for first-line use in specific populations and also the potential use of ipilimumab by patients with early-stage disease that progresses to advanced disease.

Copyright AJMC 2006-2020 Clinical Care Targeted Communications Group, LLC. All Rights Reserved.
Welcome the the new and improved, the premier managed market network. Tell us about yourself so that we can serve you better.
Sign Up