Methodology Consultation Success Story: Dr. Ashish Premkumar

The incidence of neonatal abstinence syndrome (NAS), also known as neonatal withdrawal syndrome, increased nationally from 3.4 per 1000 hospital births in 2009 to 5.8 in 2012. Recent estimates of NAS cost $1.5 billion dollars with the majority of the financial burden falling to state Medicaid programs. However, pregnancy offers a unique opportunity for women with opioid use disorder (OUD) to engage with the healthcare system and potentially initiate treatment for OUD.

Dr. Ashish Premkumar recently published a cost-effectiveness analysis comparing methadone, buprenorphine or detoxification with buprenorphine taper for management of OUD among pregnant women in Obstetrics and Gynecology.  Dr. Premkumar, an obstetrician and gynecologist in the Division of Maternal-Fetal Medicine in the Feinberg School of Medicine at Northwestern University, used the CHERISH Consultation Service to assist him in conducting this cost-effectiveness analysis. During the consultation with CHERISH Research Affiliate Dr. Joshua Barocas at Boston Medical Center, Dr. Premkumar obtained assistance in identifying resources and cost estimates to inform the model. The cost estimates from the literature review provided ranges for sensitivity analyses that identified key determinants of cost-effectiveness outcomes.

The study found that buprenorphine was the preferred strategy for OUD treatment during pregnancy, but the findings were sensitive to the costs of methadone and detoxification. The detoxification strategy had the highest rate of relapse and had three times more individuals switching to methadone due to repeated relapse or overdose than the buprenorphine strategy. Although detoxification resulted in fewer cases of NAS and fewer admissions to the neonatal intensive care unit, the higher costs of OUD relapse and methadone maintenance following relapse offset the cost savings associated with fewer NAS cases. 

Revisions to 42 CFR Patient Confidentiality Rules for Substance Use Disorder: What It Means for Health Services Researchers

In August 2019 the United States Substance Abuse and Mental Health Services Administration (SAMHSA) proposed a revision to the Federal rule that protects patient confidentiality for people with substance use disorders, referred to as 42 CFR Part 2. The sixty day comment period has ended and comments are currently under consideration. This proposal seeks to facilitate disclosure of substance use treatment records to providers, insurers, and researchers in order to improve care coordination between opioid treatment programs (OTPs) and other providers. OTPs are specialized programs that provide substance use diagnoses, treatment and referral to treatment. These include specialty treatment facilities that provide medications for opioid use disorder such as methadone.

The proposed revision clarifies what is considered a protected record to encourage record sharing in electronic medical record (EMR) systems, requires OTPs to enter dispensed medication into state prescription drug monitoring programs (PDMPs), and clarifies what information can be disclosed without additional patient consent to third parties such as insurers, government agencies, and researchers. In general, the proposed revisions would make data on substance use disorder diagnoses and treatment in EMR, PDMPs, and insurance claims datasets more available to researchers. Researchers would still be subject to existing rules protecting confidentiality of any human subjects research data.

The proposed revision aims to improve care coordination between OTPs and other providers by clarifying which records are subject to additional protections under 42 CFR Part 2 and how to best include that information in an EMR. If a patient provides consent, the OTP can disclose patient treatment records to another provider outside the OTP system in order to facilitate care coordination between the two health systems. This provider then becomes the “lawful holder” of the patient’s information. These protected records may be segmented into a separate EMR system, or the provider can transcribe the information into the EMR system. All subsequent treatment records are not subject to additional protection, thus facilitating documentation of substance use treatment in the EMR. This revision will facilitate information sharing across health systems and provide linked information regarding substance use treatment and subsequent health care utilization.

Integrating OTP records into EMR systems could provide health services researchers who gain access to these records with a greater understanding of healthcare service utilization and health outcomes among people with substance use disorder. Under the proposed revision, this information can then be re-disclosed by the lawful holder to third party payers for the purpose of payment or healthcare operations, thereby also making this data available through insurance claims databases.

Under the revised rule health services researchers will have access to more detailed information on methadone and buprenorphine prescribing by OTPs through PDMPs. PDMPs are statewide records of prescribed medication, and previously did not include medications for dispensed through OTPs in order to protect patient confidentiality. The requirement to enter patient medications for substance use disorder in the PDMPS is intended to minimize contraindicated prescribing and resulting adverse events. This change will allow health services researchers to get better information about methadone dispensing and health outcomes by linking PDMP data with other data sources. Some patient advocates are concerned that the change will have unintended consequences and discourage people with opioid use disorder from accessing OTP services; however, buprenorphine prescribed by waivered physicians outside of specialty OTPs is already included in PDMPs.

Finally, under the current rule patient information can be re-disclosed for research purposes without patient consent only if the researcher is part of a HIPAA covered entities and receives documented access authorization. This may limit data access for legitimate stakeholders, such as state or government agencies, that are not covered by HIPAA. The proposed rule allows research disclosures of OTP data from a HIPAA covered entity to researchers or organizations that are not covered by HIPAA provided there be safe guards in place for the patient confidentiality. This more closely aligns with analogous requirements for human subject research. The change would therefore facilitate data access for health services researchers in state or government agencies.

Integrating data from OTPs in EMRs, allowing greater re-disclosure to third-party payers, and including medications dispensed in OTPs in PDMPs will allow health services researchers and health economists to estimate the costs of substance use treatment, the potential increased treatment utilization, and improved healthcare outcomes. Requiring OTPs to disclose medications in the PDMPs will also provide researchers a better understanding of the utilization of MOUDs in the United States, which is likely underestimated in the current PDMPs. Expanding data access to researchers outside of HIPAA-covered entities, such as state government agencies, will provide them with access to more information for decision making. These changes will need to be implemented in ways that maintain patient confidentiality and address concerns that the data will be misused by providers and insurers to deny care or reinforce stigmatizing behaviors in the health care system.

USPSTF and CDC Recommend Expanded HCV Testing for All US Adults

The US Preventive Services Task Force (USPSTF) released a draft recommendation for hepatitis C (HCV) antibody and RNA screening in all adults ages 18 to 79. This is a departure from their current 2013 recommendation of risk-based screening, including people who inject drugs (PWID), and one-time screening in baby boomers born between 1945 and 1965.  The recommendation to expand screening into all adults stems from trends in HCV epidemiology that indicate the increase in acute HCV incidence among younger PWID. Injection drug use is the strongest risk factor for HCV and stigma may impede PWID from disclosing these risk factors. The recommendation for screening in all young adults over 18 could minimize the need for risk disclosure and reduce barriers to diagnosis. There has also been an increase in the number of reproductive aged women with HCV infection; mother-to-child vertical transmission is the main route of HCV infection among children. Screening all adults age 18-79 would diagnose individuals at earlier stages of HCV infection avoiding severe sequelae such as cirrhosis, hepatocellular carcinoma or death.

The USPSTF is responsible for developing clinical practice guidelines for prevention and screening based on a careful review of the quality and strength of existing evidence including benefits and costs. In the draft recommendation the USPSTF cites a modeling study by CHERISH Research Affiliate Joshua Barocas, MD and CHERISH HCV and HIV Core Director Benjamin Linas, MD, MPH from Boston Medical Center, and colleagues from CDC, Massachusetts Department of Public Health, and Stanford. Dr. Barocas’ study used a Monte Carlo simulation model to compare the current USPSTF guidelines for birth cohort screening to different strategies that expand screening to younger populations with increased incidence. The study estimated that compared to previously recommended birth cohort screening, expanded screening to adults 18 or older would identify 256,000 additional cases of HCV infection and lead to 280,000 additional cures and 4,400 fewer cases of hepatocellular carcinoma over the cohort lifetime with an incremental cost effectiveness ratio of $28,193/ QALY in 2016 US dollars and an overall increased life expectancy among those with HCV.

The draft evidence review supporting this new recommendation prepared by the Agency for Health Care Research & Quality cites other modeling studies in addition to the one authored by Drs. Barocas and Linas. These include another study examining the cost-effectiveness universal screening, a study authored by CHERISH Research Affiliate Sabrina Assoumou, MD, MPH of Boston Medical Center and colleagues, including Dr. Linas and Dr. Bruce Schackman and Jared Leff from Weill Cornell Medicine, examining the cost-effectiveness of one-time HCV screening for adolescents and young adults in primary care settings, and two studies examining HCV screening in prenatal care.

Similar to Dr. Barocas’ study, Eckman et al  estimated the cost-effectiveness of universal one time HCV screening for all adults 18 and older compared with the current birth cohort screening guidelines using a Markov state transition model. The study found that universal one-time HCV screening and treatment for all adults was cost-effective even at very low rates (0.07%) of HCV prevalence in the population compared with no screening or current birth-cohort screening guidelines. CHERISH Research Affiliate Dr. Assoumou’s study focused on the cost-effectiveness of one time testing among young adults and adolescents aged 15-30 years old, which includes individuals who are younger than those covered by the USPSTF recommendation under review for one-time screening in adults 18 years or older. Dr. Assoumou’s study examined different screening methods and care delivery strategies within an urban community healthcare setting, and found potential cost and effectiveness differences by provider type and screening diagnostic method (rapid assessment or venipuncture).

HCV prevalence among pregnant women in the US doubled from 2009-2014, making screening and diagnosis of HCV among pregnant women a critical opportunity for diagnosis of the mother and of children infected with HCV through vertical transmission. Two studies cited in the draft evidence review also examined HCV screening among pregnant women in prenatal care. Chaillon et al used a Markov model to examine the cost-effectiveness of universal prenatal HCV screening followed by postnatal treatment compared to background risk-based screening and found universal prenatal HCV screening among pregnant women was cost effective. Similarly, an analysis by Abriana Tasillo, CHERISH Investigator Benjamin Linas, and colleagues evaluated the cost-effectiveness of one-time prenatal screening and postnatal treatment during pregnancy compared to current practice that does not require screening. This analysis demonstrated that prenatal screening increased identification of neonates exposed to HCV at birth by 48%, increased the proportion of cases achieving SVR within 5 years by 11%, and consequently reduced HCV attributable mortality by 16%.  Together, these findings the USPSTF recommendation for prenatal screening and the potential treatment benefits of both mother and child.

In November 2019 the Centers for Disease Control and Prevention (CDC) announced it was seeking comments on new hepatitis C screening recommendations that also recommends screening at least once in a lifetime for all adults 18 or older, as well as screening for all pregnant women, in addition to risk-based screening. The CDC recommendation relies on much of the same cost-effectiveness literature cited in the USPSTF testing recommendations. The CDC stipulates that its recommendations apply to states and settings where the prevalence of hepatitis C is greater than 0.1% of the adult population, based in part on its review of cost-effectiveness literature which demonstrated that incremental cost-effectiveness ratios were sensitive to HCV prevalence. Currently, there is no state with a hepatitis C prevalence below 0.1%, and only 3 states have an HCV prevalence less than 0.1% among pregnant women according to state birth certificate data. The comment period on the CDC recommendations remains open until December 27. 2019

Increased number of children entering the foster care due to parental drug use

In a recent study published in JAMA Pediatrics, CHERISH Pilot Grant Recipient Angelica Meinhofer examined national trends in foster care entries attributable to parental drug use between 2000 and 2017. There were approximately 5 million foster care entries between 2000 and 2017, 23.38% percent of which were attributable to parental drug use. Moreover, the number of foster care entries attributable to parental drug use increased 147% between 2000 and 2017, from 39,130 to 96,672 entries. Compared with children entering the foster care system for other reasons, children entering because of parental drug use were more likely to be under 5 years old, white and from the Southern region of the US. The proportion of foster care entries related to parental drug use increased in the Midwest and non-metropolitan areas between 2000-2005 and 2012-2017. Meinhofer suggests that the opioid crisis is only one possible explanation for these trends, which may also be related to increased drug use overall, changes in child removal policies, or changes in data collection methods. The findings have economic implications for the foster care system as increased entries require more resources for high-quality foster care interventions, and a greater capacity for foster care particularly as research shows that foster care episodes are longer for children who enter foster care due to parental drug use. Meinhofer says that she “hopes that these findings will encourage researchers to investigate the implications of increased foster care entries on the foster care system, and on the health outcomes and well being of children.”

Progress of “Netflix” subscription model negotiations to pay for HCV Treatment

In 2018, the state of Louisiana spent approximately $35 million to treat 1,000 individuals with chronic Hepatitis C Virus (HCV). Unfortunately, these 1,000 treated individuals comprise only about 1% of the state’s 90,000 individuals living with HCV, including about 39,000 covered by the state’s Medicaid program or prison system. Treating everyone would cost more than “the state spends on K-12 education, Veteran’s Affairs, and Corrections combined,” according to the Secretary of the Louisiana Department of Health, University of Pennsylvania Alumna Dr. Rebekah Gee, in an article for Health Affairs. Using the Louisiana Budget Allocator developed at the Drug Pricing Lab at Memorial Sloan Kettering Cancer Center, experts estimated it would require approximately $760 million to treat everyone who has HCV in Louisiana at current HCV medication prices.

In order to increase access to HCV medication for Medicaid patients and justice-involved individuals, Dr. Gee, the Louisiana Department of Health, and the Centers for Medicaid and Medicare Services (CMS) announced in June  2019 that they have formed an agreement with Asegua Therapeutics,  the generics subsidiary of Gilead Sciences, Inc., to limit the total cost of HCV medication in exchange for unrestricted access to a generic version of Gilead’s HCV combination medication sofosbuvir/ velpatasvir for five years. Their goal is to treat 10 times more patients with HCV each year, without the yearly budget exceeding the amount they spent in 2018. After reaching this expenditure cap for Medicaid patients, Asegua would provide HCV medication for the remaining patients for free to the state of Louisiana through a supplemental rebate arrangement. This modified subscription model effectively reduces the cost per treatment but without violating the federal “best price” law that would require Asegua to provide the same price discounts on HCV medication to other Medicaid programs. Depending on the success of the deal, Louisiana could seek similar deals for other drugs, such as those used for pre-exposure prophylaxis for HIV prevention and naloxone for overdose prevention.

In July 2019, CMS approved negotiation of a similar payment model for HCV treatment in Washington State. Under Washington’s proposed model, the state would pay a fixed annual amount to a pharmaceutical manufacturer to purchase an unrestricted supply of HCV drugs. Previously, the Washington State Health Care Authority had announced that Abbvie, LLC was the apparently successful bidder in response to its request for proposal covering 30,000 people with HCV, although no details of the bid were disclosed. A CMS statement indicated that “CMS welcomes proposals from other states for state plan amendments to allow negotiation of supplemental rebates involving value based purchasing in Medicaid, and the agency has heard additional interest in a “subscription” model for Hepatitis C drugs.”

This “subscription” or “Netflix” payment model is largely based on Australia’s lump-sum remuneration model, in which the Australian government worked with pharmaceutical companies to negotiate a fixed payment over five years in exchange for unlimited volume of HCV medication. Subsequent research showed that the subscription model successfully provided medication for an additional 93,400 patients and saved the Australian government approximately $4.92 billion USD.

These efforts are aimed at achieving a global goal set by the World Health Organization to eliminate hepatitis by 2030. Several other of the 12 countries that are on track to achieve the hepatitis elimination targets – including Georgia and the United Kingdom – have negotiated with pharmaceutical companies to provide discounted or donated medication.

CHERISH Investigators and Research Affiliates Support NIDA Justice Community Opioid Innovation Network (JCOIN)

On July 24 2019, the National Institute on Drug Abuse (NIDA) announced twelve grants totaling approximately $155 million for the Justice Community Opioid Innovation Network (JCOIN) as part of the greater NIDA HEAL initiative. JCOIN will establish a network of 10 clinical research institutions, a Methodology and Advanced Analytics Resource Center (MAARC), and a Coordination and Translation Center (CTC) that will conduct studies on quality care for opioid use disorders in the criminal justice population that are disproportionately affected by the opioid crisis. Each research center will collaborate with organizations in justice settings and service providers in five or more communities to evaluate evidence-based medications and behavioral interventions for opioid use disorders in a wide variety of criminal justice settings.

The awarded clinical research institutions include the Baystate Medical Center (CHERISH Research Affiliate Peter Friedmann), Brown University, Chestnut Health Systems, Inc., Friends Research Institute, Inc., New York State Psychiatric Institute, New York University School of Medicine, Texas Christian University, University of Chicago (CHERISH Research Affiliate Harold Pollack), University of Kentucky, and Yale University. The University of Chicago will serve as the MAARC (Dr. Pollack) and George Mason University will serve as the CTC.

In establishing JCOIN, NIDA emphasized the importance of integrating rigorous economic evaluations and considering societal outcomes such as the cost of crime in order to address affordability and sustainability of evidence-based treatment interventions. CHERISH is proud that our investigators Kathryn McCollister and Sean Murphy will provide economic expertise to Baystate Medical Center (Drs. McCollister and Murphy), Chestnut Health Systems, Inc. (Dr. McCollister and Dr. Murphy as a consultant), Friends Research Institute, Inc. (Dr. Murphy), New York State Psychiatric Institute (Dr. Murphy and Dr. McCollister as a consultant), the University of Kentucky (Dr. McCollister), and Yale University (Dr. McCollister and Dr. Murphy as a consultant).