Overdose Crisis Endures, Yet Few People Receive Existing Effective Treatment

Even before Covid-19, despite enormous unmet need, life-saving buprenorphine is vastly underprescribed

(New York, NY, August 24, 2020) –Approximately half of clinicians authorized to prescribe buprenorphine for opioid use disorder (OUD), one of three medications for OUD, are actively prescribing the medication, according to a JAMA study led by researchers at The Pew Charitable Trusts, Deerfield Management Company, and RAND Corporation.

The research letter, which appeared in the August 24th online issue of JAMA Network Open, examines national opioid use disorder buprenorphine prescribing patterns by Drug Enforcement Administration (DEA)-approved patient limits.

Buprenorphine is considered one of the most effective therapies to treat OUD. In order to become an authorized prescriber of buprenorphine to treat OUD, clinicians are required to undergo special training and licensing with the Substance Abuse and Mental Health Services Administration (SAMHSA) and DEA.

The authors of the paper point out that federal regulations currently limit these waivered clinicians to treating 30, 100, or 275 patients concurrently, with clinicians limited to treating 30 or 100 patients able to request an increased limit.

Based on a national analysis of clinician databases from the DEA and SAMHSA and clinician-level prescribing information from Symphony Health, the authors found that of 55,938 waivered clinicians, only 50.9 percent wrote at least one buprenorphine prescription during the 22-month period of April 2017 through January 2019.

Median patient monthly census calculations revealed 275-patient clinicians treated 36.9% of their patient limit, while 100-patient and 30-patient clinicians treated 23.9% and 11.3% of their patient limits, respectively.

“More than 2 million people in the United States have an opioid use disorder, yet few of them receive any type of specialty treatment, including buprenorphine,” said study co-author Alexandra Duncan, senior officer with The Pew Charitable Trusts’ substance use prevention and treatment initiative. “Removing barriers to buprenorphine prescribing can help close this treatment gap and ensure that people have access to the evidence-based addiction care they need.”

In recognition that buprenorphine is an important option for patients because it eliminates the need for the daily clinic visit required of most patients receiving methadone, NYC Health and Hospitals expanded access to the medication by integrating prescribing into primary care. Additional benefits of buprenorphine are its low potential for abuse and negligible risk for overdose.

“Our finding that about half of doctors who can prescribe buprenorphine aren’t doing so makes clear that increasing the number of patients receiving it is not just about increasing the number of clinicians who can prescribe it,” added co-author Bradley Stein, Director of RAND’s Opioid Policy Center. “We need to focus efforts on increasing reimbursement for buprenorphine’s use, educating prescribers, patients, and their families about  its effectiveness, and combatting the stigma that hampers the effective treatment of opioid use disorder.”

“Leveraging multiple large databases not only allowed us to confirm earlier evidence that clinicians are prescribing below their patient limits, but also enabled us to continue to peel back the onion on the scope of this problem, said co-author Jared Anderman, director of data analytics at the Deerfield Institute, a division of Deerfield Management Company.  “We are looking forward to continuing to work with the powerful dataset we have created and identifying additional opportunities to make an impact.”

Authors of the study, titled, “Monthly Patient Volumes of Buprenorphine-Waivered Clinicians in the U.S.,” are:  Alexandra Duncan (The Pew Charitable Trusts); Jared Anderman (Deerfield Management Company); Travis Deseran (previously Deerfield Management Company); Ian Reynolds (The Pew Charitable Trusts); and Bradley D. Stein (RAND Corporation). The work was funded by The Pew Charitable Trusts and Deerfield Management Company.

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About Deerfield Management Company

Deerfield is a healthcare investment management firm committed to advancing healthcare through investment, information and philanthropy.

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Karen Heidelberger, [email protected], 212-692-7140

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Deerfielders Weigh in on a Safe Return to Work Policy Amid Covid-19 Crisis

Antibody testing provides a data-driven path to getting people back into the economy

The availability of point of care antibody testing—also known as serological testing—may provide a feasible roadmap for getting people back to work safely following the COVID-19 crisis, according to an editorial published in the journal Contemporary Clinical Trials Communications.

“You can’t stop the economy forever,” asserted Governor Cuomo in a recent news conference, according to STAT. “So we have to start to think about, does everyone stay out of work? Should young people go back to work sooner? Can we test for those who had the virus, resolved, and are now immune, and can they start to go back to work?”

Regardless of whether they already have immunity to the virus, millions of Americans may try to return to work, potentially undoing all the benefits of the shutdown, suggests the editorial. 

Antibody testing, the authors argue, could clarify a person’s status quickly in real-time and reveal whether they have been exposed to COVID-19. Accordingly, a person who mounts an IgG positive response (suggesting the presence of immunoglobulin G antibodies) would most likely now be immune to the virus and an IgM positive result would point to the process of developing immunity in someone who more recently became infected.

“Unlike the PCR tests (a measure of virus material), the immediate results and unconstrained supply of antibody tests could fundamentally change the way we manage this epidemic,” says Robert Jackson, MD, a co-author of the paper. “And from an economic perspective, it could lead to a tractable path for people to return to work. Collecting the data and tracking individuals longitudinally, in order to confirm the hypothesis, will be necessary.”

And barring any HIPAA concerns, the authors propose that persons with positive antibody tests during periods of social distancing could get a bracelet, which indicates that they are immune-protected and can return to work. Those without a bracelet would still be asked to practice social-distancing and not yet resume their normal activities. But this approach could potentially get at least some portion of the economy back running again, suggests the authors.

According to the authors, the antibody tests are cheap, easy to administer, and could be made available at every hospital.

“Broad testing is in society’s best interest,” says Alex Karnal, a co-author of the editorial. “Until we make serological tests available in a robust way, it’s as if we are flying a plane without navigation.”

Authors of the editorial, titled, “Let’s Get Americans Back to Work Again,” are: Alex Karnal, Partner and Managing Director; Robert Jackson, MD, Partner and Chief Science Officer; and Joe Pearlberg, MD, PhD, Vice President of Scientific Affairs, all at Deerfield; and Amitabh Chandra, PhD, McCance Family Professor at Harvard Business School and Weiner Professor at the Harvard Kennedy School.

A hybrid approach for prediction of event times in double-blind clinical trials

In clinical trials especially those events-driven trials, it is often of great interest to predict the timing of pre-specified landmark event accurately in order to prepare for the interim or final analyses. Both parametric and non-parametric approaches have been proposed in the literature to estimate the underlying survival functions which is the key to the prediction of future event times. However, the existing approaches are neither not applicable to double-blind clinical trials or assuming smooth survival functions which might not hold in real clinical settings. In this talk, a hybrid parametric and non-parametric approach is proposed to predict event times in double-blind clinical trials with time-to-event outcomes. A greedy algorithm is first developed to detect change points in survival functions. The survival function before the last change point is estimated non-parametrically and the tail distribution beyond the last change point is estimated parametrically. Numerical results show that the proposed approach provides accurate predictions for future event times.

Predictors of laparoscopic hysterectomy for leiomyoma surgical removal in the United States

Objectives

Leiomyomas (uterine fibroids) are benign tumors that are prevalent among women of reproductive age and affect approximately 80% of premenopausal women. Hysterectomy is one of the most common surgical procedures for removal of uterine fibroids. Laparoscopic hysterectomy (LH) has increasingly been used as an alternative to the open surgical hysterectomy (OSH). The purpose of this study was to identify predictors of LH procedures among leiomyoma patients.

Methods

The National Inpatient Sample (NIS) is the largest publicly available inpatient healthcare database in the US, containing a 20% stratified systematic random sample of all US community hospital discharges. Thirteen years of available data, 2002–2014, were used for this analysis. International Classification of Diseases 9th revision (ICD-9) codes were used to identify all records of women with primary discharge diagnosis of uterine leiomyoma who had undergone either LH or OSH. Multivariate logistic regression analysis was conducted to identify significant predictors of LH. Population sampling weights were used to extrapolate results to national estimates.

Results

There were 310,150 leiomyoma LH procedures from 2002 to 2014, corresponding to 22.5% of the total number of leiomyoma hysterectomy procedures. The mean age of patients undergoing LH was significantly higher than those undergoing OSH (45.69 years vs 43.29 years; p<0.001). After adjusting for covariates, significant predictors of LH procedures included age > 50 years (OR=3.18; 95% CI=3.57-4.07), hospital location in the West (OR=1.46; 95% CI=1.38-1.86), and hospital urban non-teaching status (OR=1.20; 95% CI=1.04-1.38).

Conclusions

The study shows that despite the advances in surgical technologies, there are very few predictors of non-conventional laparoscopic approach to leiomyoma hysterectomy. Our findings suggest that there is a differential access to LH procedures among the US population which may be, in part, a result of racial and socioeconomic differences and centralization of laparoscopy services in urban areas.

Analysis of success rates for the Center for Medicare and Medicaid’s new technology add-on payment program

Objectives

To quantify the approval, denial, and withdrawal rates and identify any predictors of success or failure for all new technology add-on payment (NTAP) applications from FY 2003 to FY 2018 in the United States.

Methods

The Center for Medicare and Medicaid (CMS) releases inpatient payment methodology rulemaking annually in the Federal Register, including details of NTAP submissions. The proposed and final rulemaking documents were analyzed to quantify the approval, denial, and withdrawal rates of all applications and determine primary reasons for denial or withdrawal from FY 2003 to FY 2018. Raw data were coded to further examine any predictors of application success such as product type, therapeutic category, manufacturer type, reapplication status, and proposed rule determination.

Results

There were 95 NTAP applications submitted over the last 15 fiscal years. Approximately 30%, 25%, and 45% of applications were approved, withdrawn prior to final rule, or denied, respectively. Inability to meet the “newness criteria” developed by CMS was the primary reason for denied and withdrawn applications. Product type, therapeutic category, and reapplication status have minor to significant impact on the approval rate of an application. However, manufacturer type and proposed rule determination have little to no impact on application outcome.

Conclusions

While there are a few factors that may positively influence the outcome of a NTAP application, the approval rates for the program are low overall. Without additional reimbursement from the NTAP program, inpatient hospitals may be deterred from adopting innovative therapies because of financial burdens. CMS and manufacturers should strive to find a better consensus for a framework that adequately incentivizes the utilization of new technologies for Medicare beneficiaries.

Trends in isolated mitral valve surgery: the changing risk profile of patients and outcomes

Abstract 00357: Open surgical repair has historically been the only corrective procedure for mitral regurgitation. There are few contemporary data examining evolving patient characteristics and surgical outcomes of mitral valve surgery. We sought to characterize trends in patient characteristics and outcomes after isolated mitral valve repair surgery over the past decade in the United States

The importance of emerging transcatheter mitral valve technologies in cost-effectiveness and post-procedure outcomes

Abstract 00165: Mitral intervention has historically been open surgical and has been limited to a small subset of patients who could tolerate surgery and where there was perceived clinical benefit. With the emergence of transcatheter mitral interventions, we sought to compare the types of patients undergoing surgical and transcatheter mitral interventions. Moreover, we sought to determine if there were any major differences in adverse events, length of stay (LOS), and cost to the healthcare system

Recent trends in percutaneous coronary intervention volume in the United States: Analysis of HCUP-NIS, 2010-2013

Objectives

Percutaneous coronary intervention (PCI) is a common major medical procedure in the United States. It has previously been estimated there are 600,000–1,000,000 PCIs performed annually, although these results are based on older data. The aim of this study was to accurately estimate the number of PCI procedures and describe potential trends in PCI use during 2010 to 2013.

Methods

The National Inpatient Sample (NIS) is the largest publicly available all-payer inpatient healthcare database in the United States, containing a 20% stratified systematic random sample of discharges from all US community hospital discharges. The most recent 4 years of available data, 2010–2013, were used for this analysis. International Classification of Diseases 9th revision (ICD-9) codes were used to identify patients undergoing PCI, as well as to segment high-risk patients based on certain diagnoses. Population sampling weights were used to extrapolate results to national estimates.

Results

There were 559,219 PCI procedures in 2010 decreasing to 519,100 in 2013, corresponding to a change of -7.2% (p<0.0001). The corresponding rate of PCIs per 10,000 population was 18.08 in 2010 and 16.40 in 2013. Despite the overall decrease in PCI volume, procedures among high-risk patients increased during this time period. PCI procedures among patients with cardiogenic shock increased from 19,932 in 2010 (3.56% of all PCIs) to 22,685 in 2013 (4.37%) and procedures among patients with left ventricular heart failure increased from 40,417 (7.23%) in 2010 to 59,110 (11.39%) in 2013. CONCLUSIONS: This study shows that the volume of PCIs in the United States has decreased in recent years, and is significantly lower than previous estimates. Despite the overall decrease in PCI volume, procedures among patients with high-risk characteristics increased during the same time period. This suggests a potential shift in the application of PCI to more severe patients.

Epidemiology of chronic kidney disease and predictors of hyperkalemia: Analysis of Nhanes 2007-2014

Chronic kidney disease (CKD) is progressive condition characterizing the gradual loss of kidney function. Patients with CKD are at high risk for hyperkalemia, which can cause severe cardiac electrophysiology alterations and sudden death. The objective of this study was to describe the prevalence of CKD among US adults and identify predictors of hyperkalemia among CKD patients during the time period 2007 to 2014.

Mitral valve disease in the United States: retrospective analysis of hospitalizations and surgical procedures using the National Inpatient Sample (World Congress on Heart Disease abstract)

Introduction

Valvular heart disease (VHDs), of which the mitral valve is frequently implicated, are collectively responsible for more than 20,000 annual deaths in the United States and the economic burden on the public health system due to VHDs is estimated in the billions of dollars.

Objective

The aim of this study was to assess the number of mitral valve disease hospitalizations and surgical procedures in the United States during the period 2010-2013.

Materials and Methods

Patient data were extracted from the Healthcare Cost and Utilization Project (HCUP) National Inpatient Sample (NIS). The NIS is the largest publicly available all-payer inpatient healthcare database in the United States, containing a 20% stratified systematic random sample of discharges from all US community hospitals. The most recent 4 years of available data, 2010-2013, were used for this analysis. Patients diagnosed with mitral valve disease were identified using the appropriate International Classification of Diseases 9th revision (ICD-9) diagnosis codes. ICD-9 procedure codes were used to identify surgeries to repair or replace the mitral valve, including transcatheter mitral valve repair (TMVR), open repair, tissue graft, and synthetic replacement. Categorical variables were analyzed using the chi-squared test, while continuous variables were analyzed using a one-way analysis of variance (ANOVA) or independent samples t-test.

Results

There were 174,2587 discharge records in 2013 with a diagnosis of mitral valve disease. Using HCUP’s sampling weights, this extrapolates to 871,290 hospitalizations in the United States. This is a slight decrease from 2010, when there were 883,933 estimated hospitalizations. The mean age of patients hospitalized for mitral valve disease increased from 71.15 (95% CI: 71.08-71.23) years in 2010 to 71.68 (95% CI: 71.61-71.76) years in 2013 (p<0.0001). 61.7% of mitral valve hospitalizations were females in 2010 compared with 59.2% in 2013 (p<0.0001). Mitral valve surgical procedures increased from 35,111 procedures in 2010 to 38,030 procedures in 2013. Concurrently, the proportion of mitral valve disease patients that underwent a surgical procedure to repair or replace the mitral valve increased from 3.5% in 2010 to 3.9% in 2013 (p<0.0001). Among elderly patients ≥80 years of age, mitral valve disease represented an increasing proportion of all hospitalizations, increasing from 6.0% in 2010 to 6.6% in 2013. Patients with a primary diagnosis of mitral valve disease who underwent a mitral valve surgical procedure were younger on average than those with a primary diagnosis of mitral valve disease who did not undergo a surgical procedure: 64.50 (95% CI: 64.31-64.69) years vs. 70.73 (95% CI: 70.51-70.95) years (p<0.0001). Conclusions This study reveals that mitral valve disease is a considerable public health problem in the United States, particularly among older adults. During 2010-2013, an increasing proportion of hospitalized patients with mitral valve disease underwent surgical procedures to repair or replace the valve. Overall, the volume of mitral valve surgical procedures increased approximately 8.3% from 2010 to 2013.