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The American Journal of Managed Care June 2016
Development of a Tethered Personal Health Record Framework for Early End-of-Life Discussions
Seuli Bose-Brill, MD; Matthew Kretovics, MPH; Taylor Ballenger, BS; Gabriella Modan, PhD; Albert Lai, PhD; Lindsay Belanger, MPH; Stephen Koesters, MD; Taylor Pressler-Vydra, MS; and Celia Wills, PhD, RN
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Renuka Tipirneni, MD, MSc; Karin V. Rhodes, MD, MS; Rodney A. Hayward, MD; Richard L. Lichtenstein, PhD; HwaJung Choi, PhD; Elyse N. Reamer, BS; and Matthew M. Davis, MD, MAPP
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Julia Thornton Snider, PhD; Seth Seabury, PhD; Janice Lopez, PharmD, MPH; Scott McKenzie, MD; Yanyu Wu, PhD; and Dana P. Goldman, PhD
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Robert. E. Mechanic, MBA, and Darren Zinner, PhD
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Adoption of New Agents and Changes in Treatment Patterns for Hepatitis C: 2010-2014
Xiaoxi Yao, PhD; Lindsey R. Sangaralingham, MPH; Joseph S. Ross, MD; Nilay D. Shah, PhD; and Jayant A. Talwalkar, MD

Adoption of New Agents and Changes in Treatment Patterns for Hepatitis C: 2010-2014

Xiaoxi Yao, PhD; Lindsey R. Sangaralingham, MPH; Joseph S. Ross, MD; Nilay D. Shah, PhD; and Jayant A. Talwalkar, MD
New hepatitis C medications have been quickly adopted into practice and increased treatment rate. The median out-of-pocket costs of new medications were relatively low.
We also examined the trends of treatment among different subpopulations and found the trend among the elderly (65 years or older) was very different than the rest of the cohort (eAppendix Figure 2 and eAppendix Table 3). Prior to 2014, only 0.5% to 1.5% of elderly patients were on treatment each quarter, but after the new medications became available, the treatment rate tremendously increased. In the last quarter of 2014, the percentage of elderly patients who were being treated was comparable to the overall population (4.4% vs 4.6%).

The predicted probabilities of receiving treatment prior and after new medications became available are shown in Table 2. Overall, the treatment rate was estimated to increase from 5.39% to 6.77%, with a significant absolute increase of 1.38%. The absolute increase was greatest among patients who had a past liver transplant (9.11%): from 5.54% to 14.65%. The absolute increase in treatment rate was also high among patients 65 years or older (4.34%); those with liver cancer (5.47%), liver disease, or cirrhosis (5.15%); and a CDCI score of 2 or more (2.95%). The predicted probability of receiving treatment significantly decreased among patients aged 18 to 40 years and 41 to 50 years, and patients with a CDCI score of 0%, –3.54%, –2.24%, and –1.12%, respectively. The increase in treatment rate was greater among male than female (1.75% vs 0.90%), black than white (1.62% vs 1.31%), poor (annual household income <$40,000) than high-income (>$100,000; 2.04% vs 0.77%), and patients living in the Midwest and Northeast than those living in the South and West (2.47%, 2.76%, 0.36%, 0.97%, respectively).

Table 3 shows the OOP costs among the 5436 treated patients. The median OOP costs of patients receiving new regimens were relatively low ($112-$340), but there were great variations and the mean costs were high ($1982-$2127). Some patients did not pay any cost OOP, whereas others paid as high as $75,831.

DISCUSSION
To the best of our knowledge, no contemporary data exists on the trends and patterns of HCV treatment in real-world clinical practice, especially in the new era of HCV treatment since December 2013. Our study is the first to examine the early adoption of new HCV treatment in a large, national, privately insured population. We observed substantial changes in treatment patterns over the past 5 years. The older treatments, ribavirin, interferon, boceprevir, and telaprevir, are essentially obsolete now, with few patients receiving these therapies at the end of 2014. Instead, patients are now almost exclusively using therapies only made available since 2013, because of the efficacy, safety, and convenience of the new medications.

Our study also found the introduction of new medications was associated with increased treatment rates, especially among those who were older and had other chronic conditions that necessitated urgent treatment. We also observed different patterns of the uptake of new medications among different subpopulations of patients. Although white and high-income patients had the highest treatment rate both before and after the new medications became available, the gaps between white and black and high- and low-income individuals were closing. The Midwest and Northeast seemed to adopt the new treatment more quickly than the South and West. Patients who were young or had few chronic conditions might be less likely to receive care. Due to the high costs of new medications, some insurers developed prior authorization programs and asked physicians to treat only patients who require immediate therapy23; this makes it difficult for young and healthy patients to obtain treatment. These patients may also be willing to hold off on treatment, with the expectation that more new HCV medications would become available and the price would drop.

In the cohort, 1948 patients received prescriptions for sofosbuvir, 781 for simeprevir, and 780 for both agents. This translates to 40% of patients receiving prescriptions for sofosbuvir and nearly everyone who received prescriptions for simeprevir was treated by the combination of the 2 agents. Although the combination of sofosbuvir and simeprevir was approved by the FDA in November 2014,24 the off-label use started right after the 2 agents were individually approved. The efficacy and safety of this combination was supported by the combination of simeprevir and sofosbuvir in a trial of patients with HCV infection,12 and may be attractive for patients who are unwilling or unable to undergo interferon-based regimens. The most recent American guideline includes the combined therapy as one of the recommended regimens.16 Nearly half the patients receiving the combination had other complex chronic conditions, such as depression (14.5%), liver cancer (2.9%), liver disease or cirrhosis (30.2%), and liver transplant (5.3%). These comorbidities were captured during the 12-month baseline, so it is possible that patients’ diseases information was not fully captured. It is also possible that patients developed new conditions during follow-up. Despite the potentially underestimated prevalence of comorbidities, it is clear many patients receiving the combination did not have any severe chronic conditions other than HCV. Interestingly, the payers seemed to cover costs of the combined regimen very well; the average OOP costs were only $100 higher for the combined regimen than the regimen that was not combined. In fact, the median cost was lower in the combined regimen ($300 vs $340).

Overall, the OOP costs were affordable for many of the patients who received the new therapies. The median cost for the ledipasvir/sofosbuvir regimen was only $112—much lower than any previous regimen. Despite the high wholesale prices, due to the effectiveness of treatment as well as the expected reductions in downstream costs associated with averted progression of liver disease, the new standard HCV treatments might be cost-effective in most patients.25-28 Therefore, some insurers might be willing to cover most of the costs. However, the OOP costs varied a lot among patients, and some patients had to pay approximately $35,000 to $76,000 for the new regimens. In this study, we did not use a multivariable regression model to assess the independent role of new medications on OOP costs. One reason is that new medications are available to broader patient populations than old regimens. Moreover, patients who received newer agents right after the medications became available are often those who had good insurance coverage.

Limitations

One limitation of this study is that we could not fully capture patients’ past treatment history. A patient whose previous treatment failed might make decisions differently regarding whether to receive another treatment and which treatment to receive, compared with a treatment-naïve patient. Although we excluded patients who received treatment at baseline, it is possible some patients may have been treated prior to the baseline or prior to their enrollment in the health plan. However, the percentage of patients who underwent HCV treatment has been very low, especially before 2011, so there should be very few patients in our cohort who were previously treated.

Another limitation is that when estimating the OOP costs, we only considered the medication costs. We did not consider the OOP costs associated with interferon injection performed by providers, so we may have underestimated the costs of the interferon. However, only approximately 1% of claims were injections performed by health professionals. Additionally, the estimated OOP costs may not accurately reflect the costs per treatment regimen. Some patients may receive multiple treatments during follow-up, some may discontinue treatment, not comply with treatment, or their follow-up may end before finishing treatment. We conducted a sensitivity test that included only compliant patients who received a single treatment episode and finished at least 12 weeks of treatment. We excluded patients who received multiple regimens and who had a very short (<77days) or long treatment period (>365 days), and who had a proportion of days covered less than 80% (eAppendix Table 4). The estimated costs per regimen using this method were similar to the results in Table 3, except for ledipasvir/sofosbuvir. The median costs of ledipasvir/sofosbuvir increased from $112 to $180, and the mean increased from $1982 to $3030. Because ledipasvir/sofosbuvir became available in October 2014, patients who initiated treatment in November and December 2014 would not be able to finish treatment by the end of the year. Therefore, we did not capture the whole costs for some patients on ledipasvir/sofosbuvir.

CONCLUSIONS
The new HCV antiviral medications have been quickly adopted into practice; they are associated with increased treatment rates, especially among the elderly and patients with multiple chronic conditions that necessitate urgent treatment, but also make them intolerant or ineligible for previous interferon-based regimens. In this study, we did not include Viekira Pak, another new HCV medication approved by the FDA in December 2014. This new drug, developed by AbbVie Inc, has become a strong competitor of Harvoni and Sovaldi, which were developed by Gilead Sciences Inc. With more new medications available and increasing competition, the changes in treatment patterns and affordability will continue to evolve. 

Author Affiliations: Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery (XY, LRS, NDS, JAT), Rochester, MN; Optum Labs (NDS), Boston, MA; Yale University School of Medicine (JSR), New Haven, CT; Yale University School of Public Health (JSR), New Haven, CT; Division of Health Care Policy and Research (NDS) and Division of Gastroenterology and Hepatology (JAT), Mayo Clinic, Rochester, MN.

Source of Funding: The study is funded by Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, which has no role in the design and conduct of the study; collection, management, and analysis of the data; or preparation, review, and approval of the manuscript.

Author Disclosures: Dr Ross receives support through Yale University, from Medtronic Inc and Johnson and Johnson, to develop methods of clinical trial data sharing; from CMS to develop and maintain performance measures that are used for public reporting; and from the FDA to develop methods for postmarket surveillance of medical devices. Dr Ross is also supported by the National Institute on Aging (K08 AG032886) and by the American Federation for Aging Research through the Paul B. Beeson Career Development Award Program. The remaining authors report no relationship or financial interest with any entity that would pose a conflict of interest with the subject matter of this article.

Authorship Information: Concept and design (XY, LRS, JSR, NDS, JAT); acquisition of data (XY, LRS); analysis and interpretation of data (XY, LRS, JSR, NDS, JAT); drafting of the manuscript (XY, LRS, JAT); critical revision of the manuscript for important intellectual content (XY, LRS, JSR, NDS, JAT); statistical analysis (XY); obtaining funding (NDS); administrative, technical, or logistic support (NDS, LRS); and supervision (NDS, JAT).

Address correspondence to: Xiaoxi Yao, PhD, Research Associate, Mayo Clinic, Center for the Science of Health Care Delivery, 200 First Street SW, Rochester, MN 55905. E-mail: yao.xiaoxi@mayo.edu.
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