Center for Drug Safety and Effectiveness

Baltimore, MD, United States

Center for Drug Safety and Effectiveness

Baltimore, MD, United States
Time filter
Source Type

Tung Y.-C.,National Taiwan University | Chang G.-M.,Cardinal Tien Hospital | Chang G.-M.,Fu Jen Catholic University | Chang H.-Y.,Center for Drug Safety and Effectiveness | Yu T.-H.,National Taipei University of Nursing and Health Sciences
PLoS ONE | Year: 2017

Background Thirty-day readmission rates after acute myocardial infarction (AMI) and heart failure are important patient outcome metrics. Early post-discharge physician follow-up has been promoted as a method of reducing 30-day readmission rates. However, the relationships between early post-discharge follow-up and 30-day readmission for AMI and heart failure are inconclusive. We used nationwide population-based data to examine associations between 7-day physician follow-up and 30-day readmission, and further associations of 7- day same physician (during the index hospitalization and at follow-up) and cardiologist follow- up with 30-day readmission for non-ST-segment-elevation myocardial infarction (NSTEMI) or heart failure. Methods We analyzed all patients 18 years or older with NSTEMI and heart failure and discharged from hospitals in 2010 in Taiwan through Taiwan's National Health Insurance Research Database. Cox proportional hazard models with robust sandwich variance estimates and propensity score weighting were performed after adjustment for patient and hospital characteristics to test associations between 7-day physician follow-up and 30-day readmission. Results The study population for NSTEMI and heart failure included 5,008 and 13,577 patients, respectively. Early physician follow-up was associated with a lower hazard ratio of readmission compared with no early physician follow-up for patients with NSTEMI (hazard ratio [HR], 0.47; 95% confidence interval [CI], 0.39±0.57), and for patients with heart failure (HR, 0.54; 95% CI, 0.48±0.60). Same physician follow-up was associated with a reduced hazard ratio of readmission compared with different physician follow-up for patients with NSTEMI (HR, 0.56; 95% CI, 0.48±0.65), and for patients with heart failure (HR, 0.69; 95% CI, 0.62± 0.76). Conclusions For each condition, patients who have an outpatient visit with a physician within 7 days of discharge have a lower risk of 30-day readmission. Moreover, patients who have an outpatient visit with the same physician within 7 days of discharge have a much lower risk of 30- day readmission. © 2017 Tung et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Layton J.B.,University of North Carolina at Chapel Hill | Kim Y.,University of Chicago | Alexander G.C.,Center for Drug Safety and Effectiveness | Emery S.L.,University of Chicago
JAMA - Journal of the American Medical Association | Year: 2017

IMPORTANCE Testosterone initiation increased substantially in the United States from 2000 to 2013, especially among men without clear indications. Direct-to-consumer advertising (DTCA) also increased during this time. OBJECTIVE To investigate associations between televised DTCA and testosterone testing and initiation in the United States. DESIGN, SETTING, AND POPULATION Ecologic study conducted in designated market areas (DMAs) in the United States. Monthly testosterone advertising ratings were linked to DMA-level testosterone use data from 2009-2013 derived from commercial insurance claims. Associations between DTCA and testosterone testing, initiation, and initiation without recent baseline tests were estimated using Poisson generalized estimating equations. EXPOSURES Monthly Nielsen ratings for testosterone DTCA in the 75 largest DMAs. MAIN OUTCOMES AND MEASURES (1) Rates of new serum testosterone testing; (2) rates of testosterone initiation (in-office injection, surgical implant, or pharmacy dispensing) for all testosterone products combined and for specific brands; and (3) rates of testosterone initiation without recent serum testosterone testing. RESULTS Of 17 228 599 commercially insured men in the 75 DMAs, 1 007 990 (mean age, 49.6 [SD, 11.5] years) had new serum testosterone tests and 283 317 (mean age, 51.8 [SD, 11.3] years) initiated testosterone treatment. Advertising intensity varied by geographic region and time, with the highest intensity seen in the southeastern United States and with months ranging from no ad exposures to a mean of 13.6 exposures per household. Nonbranded advertisements were common prior to 2012, with branded advertisements becoming more common during and after 2012. Each household advertisement exposure was associated with a monthly increase in rates of new testosterone testing (rate ratio [RR], 1.006; 95%CI, 1.004-1.008), initiation (RR, 1.007; 95%CI, 1.004-1.010), and initiation without a recent test (RR, 1.008; 95%CI, 1.002-1.013). Mean absolute rate increases were 0.14 tests (95%CI, 0.09-0.19), 0.05 new initiations (95%CI, 0.03-0.08), and 0.02 initiations without a recent test (95%CI, 0.01-0.03) per 10 000 men for each monthly ad exposure over the entire period. CONCLUSIONS AND RELEVANCE Among US men residing in the 75 designated market areas, regional exposure to televised direct-to-consumer advertising was associated with greater testosterone testing, new initiation, and initiation without recent testing. Copyright 2017 American Medical Association. All rights reserved.

Qato D.M.,University of Illinois at Chicago | Wilder J.,University of Illinois at Chicago | Schumm L.P.,University of Chicago | Gillet V.,University of Chicago | Alexander G.C.,Center for Drug Safety and Effectiveness
JAMA Internal Medicine | Year: 2016

IMPORTANCE: Prescription and over-the-counter medicines and dietary supplements are commonly used, alone and together, among older adults. However, the effect of recent regulatory and market forces on these patterns is not known. OBJECTIVES: To characterize changes in the prevalence of medication use, including concurrent use of prescription and over-the-counter medications and dietary supplements, and to quantify the frequency and types of potential major drug-drug interactions. DESIGN, SETTING, AND PARTICIPANTS: Descriptive analyses of a longitudinal, nationally representative sample of community-dwelling older adults 62 to 85 years old. In-home interviews with direct medication inspection were conducted in 2005-2006 and again in 2010-2011. The dates of the analysis were March to November 2015.We defined medication use as the use of at least 1 prescription or over-the-counter medication or dietary supplement at least daily or weekly and defined concurrent use as the regular use of at least 2 medications.We used Micromedex to identify potential major drug-drug interactions. MAIN OUTCOMES AND MEASURES: Population estimates of the prevalence of medication use (in aggregate and by therapeutic class), concurrent use, and major drug-drug interactions. RESULTS: The study cohort comprised 2351 participants in 2005-2006 and 2206 in 2010-2011. Their mean age was 70.9 years in 2005-2006 and 71.4 years in 2010-2011. Fifty-three percent of participants were female in 2005-2006, and 51.6%were female in 2010-2011. The use of at least 1 prescription medication slightly increased from 84.1%in 2005-2006 to 87.7%in 2010-2011 (P = .003). Concurrent use of at least 5 prescription medications increased from 30.6%to 35.8% (P = .02). While the use of over-the-counter medications declined from 44.4%to 37.9%, the use of dietary supplements increased from 51.8%to 63.7%(P < .001 for both). There were clinically significant increases in the use of statins (33.8% to 46.2%), antiplatelets (32.8%to 43.0%), and omega-3 fish oils (4.7%to 18.6%) (P < .05 for all). In 2010-2011, approximately 15.1%of older adults were at risk for a potential major drug-drug interaction compared with an estimated 8.4%in 2005-2006 (P < .001). Most of these interacting regimens involved medications and dietary supplements increasingly used in 2010-2011. CONCLUSIONS AND RELEVANCE: In this study, the use of prescription medications and dietary supplements, and concurrent use of interacting medications, has increased since 2005, with 15%of older adults potentially at risk for a major drug-drug interaction. Improving safety with the use of multiple medications has the potential to reduce preventable adverse drug events associated with medications commonly used among older adults. Copyright 2016 American Medical Association. All rights reserved.

Hwang C.S.,Center for Drug Safety and Effectiveness | Chang H..-Y.,Center for Drug Safety and Effectiveness | Alexander G.C.,Center for Drug Safety and Effectiveness | Alexander G.C.,Johns Hopkins Hospital
Pharmacoepidemiology and Drug Safety | Year: 2015

Purpose: We quantified the degree to which the August 2010 reformulation of abuse-deterrent OxyContin affected its use, as well as the use of alternative extended-release and immediate-release opioids. Methods: We used the IMS Health National Prescription Audit, a nationally representative source of prescription activity in the USA, to conduct a segmented time-series analysis of the use of OxyContin and other prescription opioids. Our primary time period of interest was 12months prior to and following August 2010. We performed model checks and sensitivity analyses, such as adjusting for marketing and promotion, using alternative lag periods, and adding extra observation points. Results: OxyContin sales were similar before and after the August 2010 reformulation, with approximately 550000 monthly prescriptions. After adjusting for declines in the generic extended-release oxycodone market, the formulation change was associated with a reduction of approximately 18000 OxyContin prescription sales per month (p=0.02). This decline corresponded to a change in the annual growth rate of OxyContin use, from 4.9% prior to the reformulation to -23.8% during the year after the reformulation. There were no statistically significant changes associated with the sales of alternative extended-release (p=0.42) or immediate-release (p=0.70) opioids. Multiple sensitivity analyses supported these findings and their substantive interpretation. Conclusions: The market debut of abuse-deterrent OxyContin was associated with declines in its use after accounting for the simultaneous contraction of the generic extended-release oxycodone market. Further scrutiny into the effect of abuse-deterrent formulations on medication use and health outcomes is vital given their popularity in opioid drug development. © 2014 John Wiley & Sons, Ltd.

Chang H.-Y.,Center for Drug Safety and Effectiveness | Daubresse M.,Center for Drug Safety and Effectiveness | Stuart E.A.,Center for Drug Safety and Effectiveness | Alexander G.C.,Center for Drug Safety and Effectiveness | Alexander G.C.,Johns Hopkins Hospital
JAMA Internal Medicine | Year: 2015

Importance: Prescription Drug Monitoring Program (PDMP) and pill mill laws are among the principal means states use to reduce prescription drug abuse and diversion, yet little high-quality evidence exists regarding their effect. Objective: To quantify the effect of Florida's PDMP and pill mill laws on overall and high-risk opioid prescribing and use. Design, Setting, and Participants: We applied comparative interrupted time-series analyses to IMS Health LifeLink LRx data to characterize the effect of PDMP and pill mill law implementation on a closed cohort of prescribers, retail pharmacies, and patients from July 2010 through September 2012 in Florida (intervention state) compared with Georgia (control state). We conducted sensitivity analyses, including varying length of observation and modifying requirements for continuous observation of individuals throughout the study period. Main Outcomes and Measures: Total opioid volume, mean morphine milligram equivalent (MME) per transaction, mean days' supply per transaction, and total number of opioid prescriptions dispensed. Analyses were conducted per prescriber and per patient, in aggregate and after stratifying by volume of baseline opioid prescribing for prescribers and use for patients. Results: From July 2010 through September 2012, a cohort of 2.6 million patients, 431 890 prescribers, and 2829 pharmacies was associated with approximately 480 million prescriptions in Florida and Georgia, 7.7% of which were for opioids. Total monthly opioid volume, MME per transaction, days' supply, and prescriptions dispensed were higher in Florida than Georgia before implementation. Florida's laws were associated with statistically significant declines in opioid volume (2.5 kg/mo, P < .05; equivalent to approximately 500 000 5-mg tablets of hydrocodone bitartrate per month) and MME per transaction (0.45mg/mo, P < .05), without any change in days' supply. Twelve months after implementation, the policies were associated with approximately a 1.4% decrease in opioid prescriptions, 2.5% decrease in opioid volume, and 5.6% decrease in MME per transaction. Reductions were limited to prescribers and patients with the highest baseline opioid prescribing and use. Sensitivity analyses, varying time windows, and enrollment criteria supported the main results. Conclusions and Relevance: Florida's PDMP and pill mill laws were associated with modest decreases in opioid prescribing and use. Decreases were greatest among prescribers and patients with the highest baseline opioid prescribing and use. Copyright © 2015 American Medical Association. All rights reserved.

Turner L.W.,Center for Drug Safety and Effectiveness | Nartey D.,Center for Drug Safety and Effectiveness | Stafford R.S.,Stanford University | Singh S.,Center for Drug Safety and Effectiveness | And 3 more authors.
Diabetes Care | Year: 2014

OBJECTIVE: Type 2 diabetes is increasingly common and associated with substantial morbidity and mortality. This study examines trends in the patterns and costs of drug treatment of type 2 diabetes from 1997 to 2012. RESEARCH DESIGN AND METHODS: We conducted descriptive analyses of cross-sectional data using the IMS Health National Disease and Therapeutic Index, a nationally representative audit of ambulatory physician practices in the U.S. We focused on visits for diabetes among patients 35 years of age or older. We used the IMS Health National Prescription Audit of pharmacy dispensing to derive information about drug expenditures. RESULTS: Ambulatory diabetes visits increased from 23 million treatment visits in 1997 (95% CI 21-25) to 35 million (32-37) in 2007 and declined to 31 million visits by 2012 (27-31). Between 1997 and 2012 biguanide use increased, from 23% (20-26) to 53% (50-56) of treatment visits. Glitazone use grew from 6% (4-8) in 1997 (41% [39-43] of all visits in 2005), but declined to 16% (14-18) by 2012. Since 2005, dipeptidyl peptidase-4 (DPP-4) inhibitor use increased steadily, representing 21% (18-23) of treatment visits by 2012. Glucagon-like peptide 1 (GLP-1) agonists accounted for 4% of treatment visits in 2012. Visits where two or more drug compounds were used increased nearly 40% from 1997 to 2012. Between 2008 and 2012, drug expenditures increased 61%, driven primarily by use of insulin glargine and DPP-4 inhibitors. CONCLUSIONS: Declining sulfonylurea and glitazone use has been offset by increases in DPP-4 inhibitor use and, to a lesser degree, use of GLP-1 agonists. Treatment of diabetes has grown in complexity while older treatments continue to be replaced or supplemented by newer therapies. © 2014 by the American Diabetes Association.

News Article | February 23, 2017

More than two in five people receiving buprenorphine, a drug commonly used to treat opioid addiction, are also given prescriptions for other opioid painkillers - and two-thirds are prescribed opioids after their treatment is complete, a new Johns Hopkins Bloomberg School of Public Health study suggests. The findings, published Feb. 23 in the journal Addiction, demonstrate the need for greater resources devoted to medication-assisted treatment, a common clinical tool to address the epidemic. The idea behind medication-assisted treatment is that patients are given low-dose opioids that produce some of the effects of opioids while staving off physical withdrawal symptoms. The low-dose opioids produce weaker effects than drugs such as oxycodone or heroin, which come with the risk of addiction and overdose. With medication-assisted treatment, rigorous studies have shown that patients are more able to remain healthy and productive members of society. Historically, the most common drug to treat opioid use disorders has been methadone, though over the past 15 years, buprenorphine, a shorter-acting opioid similar to methadone, has been increasingly used instead. For this study, the researchers looked at prescriptions for buprenorphine and Suboxone, a combination of buprenorphine and naloxone, an anti-overdose medication. Rather than requiring a special clinic like methadone does, buprenorphine can be prescribed in a doctor's office, making it accessible to more patients. "Policymakers may believe that people treated for opioid addiction are cured, but people with substance use disorders have a lifelong vulnerability, even if they are not actively using," says study leader G. Caleb Alexander, MD, MS, an associate professor of epidemiology at the Johns Hopkins Bloomberg School of Public Health and the co-director of the School's Center for Drug Safety and Effectiveness. "Our findings highlight the importance of stable, ongoing care for these patients." Increases in prescription opioid use over the past two decades have led to an epidemic of addiction, injuries and deaths in the United States. In 2013, providers wrote nearly 250 million opioid prescriptions, enough to supply every adult in the United States with a bottle of pills. While it is sometimes appropriate for a patient to receive a prescription opioid during medication-assisted treatment - patients who are in acute pain from a major trauma or surgery may require short-term prescription opioids in addition to their medication-assisted treatment - the researchers say they are concerned to see such high rates of combined use of these products. This pattern suggests that many patients do not have well-coordinated treatment for opioid use disorders and chronic pain, which could lead to higher rates of relapse or overdose, Alexander says. For their study, Alexander and his colleagues examined pharmacy claims for more than 38,000 new buprenorphine users who filled prescriptions between 2006 and 2013 in 11 states. They looked at non-buprenorphine opioid prescriptions before, during, and after each patient's first course of buprenorphine treatment, which typically lasted between one to six months. Even though there are no universally agreed-upon guidelines regarding the optimal length of treatment, most people discontinued buprenorphine within three months. They found that 43 percent of patients who received buprenorphine filled an opioid prescription during treatment and 67 percent filled an opioid prescription during the 12 months following buprenorphine treatment. Most patients continued to receive similar amounts of opioids before and after buprenorphine treatment. Because the study data lacked information on patients' use of illegal opioids like heroin, the results likely underestimate the proportion of patients using opioids during and after buprenorphine treatment. "The statistics are startling," says Alexander, "but are consistent with studies of patients treated with methadone showing that many patients resume opioid use after treatment." Recent federal efforts have tried to improve the availability of medication-assisted treatment, so providing ongoing professional education and support to these providers will be important. "Unlike methadone, buprenorphine can be prescribed for opioid use disorders in primary care, so it is an important treatment option for clinicians and patients to have," says study co-author Matthew Daubresse, a doctoral student in the Department of Epidemiology at the Bloomberg School. "But many patients, especially those with shorter lengths of treatment, appear to be continuing to use prescription opioids during and after buprenorphine treatment. We need to find better ways to keep patients engaged in long-term treatment, and these efforts couldn't be more urgent given how many Americans continue to die or get injured from opioids." "Non-Buprenorphine Opioid Utilizations Among Patients Using Buprenorphine" was written by Matthew Daubresse, Brendan Saloner, Harold A. Pollack and G. Caleb Alexander. The work was funded by the Centers for Disease Control and Prevention under Cooperative Agreement U01CE002499. Alexander is chair of the FDA's Peripheral and Central Nervous System Advisory Committee, serves as a paid consultant to a mobile start-up PainNavigator, serves as a consultant to QuintileIMS and serves on its advisory board. This arrangement has been reviewed and approved by Johns Hopkins University in accordance with its conflict of interest policies.

News Article | December 15, 2016

Pilloried for their role in the epidemic of prescription painkiller abuse, drugmakers are aggressively pushing their remedy to the problem: a new generation of harder-to-manipulate opioids that have racked up billions in sales, even though there's little proof they reduce rates of overdoses or deaths. More than prescriptions are at stake. Critics worry the drugmakers' nationwide lobbying campaign is distracting from more productive solutions and delaying crucial efforts to steer physicians away from prescription opioids - addictive pain medications involved in the deaths of more than 165,000 Americans since 2000. "If we've learned one lesson from the last 20 years on opioids it's that these products have very, very high inherent risks," said Dr. Caleb Alexander, co-director of Johns Hopkins University's Center for Drug Safety and Effectiveness. "My concern is that they'll contribute to a perception that there is a safe opioid, and there's no such thing as a fully safe opioid." The latest drugs - known as abuse-deterrent formulations, or ADFs - are generally harder to crush or dissolve, which the drugmakers tout as making them difficult to snort or inject. But they still are vulnerable to manipulation and potentially addictive when simply swallowed. National data from an industry-sponsored tracking system also show drug abusers quickly drop the reformulated drugs in favor of older painkillers or heroin. In the last two years, pharmaceutical companies have made a concerted under-the-radar push for bills benefiting the anti-abuse opioids in statehouses and in Congress, where proposed legislation would require the Food and Drug Administration to replace older opioids with the new drugs. The lobbying push features industry-funded advocacy groups and physicians, along with grieving family members, who rarely disclosed the drugmakers' ties during their testimony in support of the drugs. Besides the tamper-resistant pills, ADF opioids are being rolled out in other forms, including injectable drugs and pills that irritate users when they're snorted or contain substances that counteract highs. Making painkillers harder to abuse is a common-sense step. But it's also a multibillion-dollar sales opportunity, offering drugmakers the potential to wipe out lower-cost generic competitors and lock in sales of their higher-priced versions, which cost many times more than conventional pills. The big companies hold multiple patents on the reformulated drugs, shielding them from competition for years - in some cases decades. Though abuse-deterrent painkillers represented less than 5 percent of all opioids prescribed last year, they generated more than $2.4 billion in sales, or roughly a quarter of the nearly $10 billion U.S. market for the drugs, according to IMS Health. The field is dominated by Purdue Pharma's OxyContin, patent-protected until 2030. "We at Purdue make certain that prescribers and other stakeholders understand that opioids with abuse-deterrent properties won't stop all prescription drug abuse, but they are an important part of the comprehensive approach needed to address this public health issue," Purdue spokesman Robert Josephson said in a statement. Like a spokeswoman for Pfizer Inc., Josephson also noted that some public health officials, including the Food and Drug Administration, have endorsed using ADFs. "We need every tool that we can have in our toolbox," said Kentucky state Rep. Addia Wuchner, a Republican who has worked on several bills to benefit reformulated opioids. "The extra steps are worth the effort in order to prevent this escalation of more addiction." The current industry campaign draws on the same 50-state strategy that painkiller manufacturers successfully deployed to help kill or weaken measures aimed at stemming the tide of prescription opioids, a playbook The Associated Press and Center for Public Integrity exposed in September. The reporting detailed how opioid drugmakers and the nonprofits they help fund spent more than $880 million on lobbying and political contributions at the state and federal level over the past decade, eight times what the gun lobby reported for the same period. The money represents the drugmakers' spending on all their legislative interests, including opioids. The FDA has approved a handful of the reformulated drugs but has not yet concluded that any reduce rates of addiction, abuse or death, and the evidence gap has led to diverging views among health authorities. Whereas FDA regulators emphasize the potential promise of reformulated painkillers, other government officials stress that they contain the same heroin-like ingredients as traditional opioids. An estimated 78 Americans die from heroin and prescription opioid overdoses every day. "'Abuse-deterrent' sounds to people sometimes like 'Oh, maybe it's not addictive.' But it's no less addictive," said Dr. Tom Frieden, head of the Centers for Disease Control and Prevention. Survey results published this year in the Clinical Journal of Pain showed nearly half of U.S. physicians incorrectly believed that reformulated opioids are less addictive than their predecessors. Many experts see a key role for ADFs in reducing the number of people who first begin abusing opioids, and some say the abuse-deterrent formulations should be the default painkiller for patients with histories of drug use, anxiety or depression. But even they worry that some drugmakers are overselling the technology. They stress that separate measures are needed for the majority of opioid abusers who ingest the pills orally. "The way they're handling the ADF is that this is the answer. And it's not the answer - it's part of the bigger puzzle," said Theodore Cicero, a psychiatry professor at Washington University in St. Louis, who has authored several studies on the drugs. 'You can't put a price tag on anybody's life' Two years after the overdose that killed her 21-year-old son, Terri Bartlett traveled to Illinois' state capital to champion an unlikely cause: revamped painkillers. Bartlett's son Michael became hooked on Vicodin and later graduated to heroin. In emotional testimony last year, she urged lawmakers to support a bill that would prioritize the new harder-to-crush pills, saying she believed her son would still be alive if abuse-deterrent formulations had been on the market then. "You can't put a price tag on anybody's life," she said. Bartlett didn't know then that she had been recruited into a wide-ranging lobbying campaign. A public relations firm hired by OxyContin-maker Purdue had helped recruit her to support the bill, along with local sheriffs and fire chiefs. Her words, and similar testimony from parents of drug abusers elsewhere, reflect a tactic used by the drugmakers across the country. For instance, Purdue paid nearly $95,000 for similar lobbying efforts in New York, state records show. And the industry's fingerprints are easy to spot in other areas. Of more than 100 bills dealing with the drugs introduced in 35 states in 2015 and 2016, at least 49 featured nearly identical language requiring insurers to cover abuse-deterrent drugs, according to an analysis of data from Quorum, a legislative tracking service. Several of the bill sponsors said they received the wording from pharmaceutical lobbyists. Since 2012, at least 21 bills related to the drugs have become law, including five that require insurers to pay for the more expensive drugs in Maine, Maryland, Massachusetts, Florida and West Virginia. Wins in such states will give drugmakers momentum to successfully push for copycat laws elsewhere, noted Paul Kelly, a federal lobbyist who has worked on multistate lobbying campaigns for drugstores and major retailers. "It's like a foot in the door," he said. Drugmakers have found fierce opposition to their ADF legislation from insurers and employers who would be on the hook for the far pricier opioid variations. The Illinois bill - and the 48 strikingly similar measures in other states - would require insurers to cover the drugs in the same way as other opioids, which the insurance companies argue would allow drugmakers to charge whatever they want for them. "That is not the best use of our medical care resources," Vernon Rowen, vice president of state government affairs for the insurance company Aetna, told Illinois lawmakers after Bartlett testified. "It totally eliminates our ability to negotiate discounts with manufacturers." New York Gov. Andrew Cuomo and New Jersey Gov. Chris Christie both vetoed such insurance mandates in the past year, citing the high costs and lack of evidence that the drugs help. Federal health officials also have pushed back against requirements to cover the drugs, citing the "staggering" costs. For example, a 30-day supply of Pfizer's abuse-deterrent Embeda, a combination drug containing morphine, costs $268, while a 30-day supply of a generic morphine costs roughly $38, according to data compiled by Truven Health Analytics, a company that tracks drug prices set by manufacturers. The Department of Veterans Affairs' Dr. Bernie Good estimated that converting the 8.8 million patient system exclusively to the new reformulations would increase opioid spending more than tenfold, to over $1.6 billion annually. Good, who co-directs the VA's program for medication safety, said the vast majority of veterans are not at risk for snorting or injecting their medications. "Would the excess money to pay for abuse-deterrent products - mostly to pay for it in cases where it wouldn't be necessary - be better spent for drug treatment centers?" he asked at a recent federal meeting on the drugs. Federal estimates say at least 2.2 million Americans are addicted to prescription opioids or heroin, yet only one in five actually receives treatment, according to a Surgeon General's report published last month. That's despite some $35 billion already spent annually on substance abuse programs by private and public health providers. State lawmakers who support the abuse-deterrent bills often defend them as an important piece of solving the opioid puzzle, preventing more costly overdoses and hospitalizations. And Fred Brason, executive director of Project Lazarus, a North Carolina-based group that promotes anti-addiction policies in several states, called the focus on the drugs' cost too narrow. "You're already spending that money at the back end," he said. "You're spending it at the emergency department." He also noted the costs of addiction treatment. When critics raise alarms about higher costs and limited evidence, drugmakers can rely on groups they support financially to argue their side, including the National Association of Drug Diversion Investigators, the Academy of Integrative Pain Management and the Partnership for Drug-Free Kids. Representatives from those groups have testified in favor of abuse-deterrent legislation in at least seven states. NADDI president Charlie Cichon acknowledged his group receives funds from several ADF-makers, but said it views the drugs as a proven part of the solution to the opioid crisis. "We're not testifying for Purdue Pharma's product or Endo's product," he said. And Bob Twillman, executive director of the Academy, said, "Increased use of abuse-deterrent opioids makes it more likely that those patients who need opiates to treat their pain will be able to get them." The Partnership for Drug-Free Kids did not respond to multiple requests for comment. Physicians with financial ties to drugmakers play similar roles. Dr. Gareth Shemesh, a pain specialist, testified in support of a Colorado bill last year brought to the sponsoring legislator by Pfizer. Shemesh had received more than $13,500 from Pfizer that year in speaking fees, travel and meals, and more than $5,000 from Purdue the year before. He did not respond to repeated calls for comment, but Pfizer said he was not paid to testify and did not speak on behalf of any specific product. Purdue and Pfizer also have ramped up contributions to the Republican and Democratic attorneys general associations, which raise unlimited funds to help elect AGs across the country. In 2015 and 2016, they gave a total of $950,000 - more than in the previous four years combined. To date, 51 attorneys general from U.S. states and territories have signed at least one of two National Association of Attorneys General letters to the FDA, urging the agency to favor abuse-deterrent drugs. The pro-ADF playbook even includes a bit of political theater. In at least seven states, lawmakers or advocates have pounded the reformulated pills with hammers to demonstrate how difficult they are to smash. In Illinois, it was Democratic Rep. Sara Feigenholtz wielding the hammer on the same committee that heard Terri Bartlett's testimony. The main sponsor of the bill prioritizing ADFs, Feigenholtz ranked second-highest among legislative recipients of money from Pfizer since the start of 2010, according to an analysis of data from the National Institute on Money in State Politics. The $6,200 she received during that period was more than she had received in the 14 previous years combined. Her bill passed the committee but later stalled in the Legislature and remains pending. She did not return multiple requests for comment. Pfizer said its contributions to Feigenholtz go back 20 years and it would be "inaccurate and misleading" to suggest a tie to any one piece of legislation. Bartlett said she doesn't mind that Purdue was ultimately responsible for her invitation to testify, even though she didn't know that at the time. She still supports the bill. "I want to believe that in every pharmaceutical company there still remains some sort of humanity," she said. "Saving life is expensive." 'An addict can find a way' The FDA has walked a careful line on the new drugs, promoting them as a promising approach to discouraging abuse while acknowledging their real-world benefits remain largely theoretical. Earlier this year, the agency highlighted the drugs in its "opioids action plan," issued after scathing criticism from some members of Congress that the FDA wasn't doing enough to combat the epidemic. Thus far, the agency has approved seven drugs with labeling suggesting they are "expected to" discourage abuse, based on studies conducted by pharmaceutical companies. But the FDA has not yet concluded that any of the products have a "real-world impact" on measures like overdose or death, according to Dr. Douglas Throckmorton, an agency deputy director. He and other regulators predict, however, that the reformulations will eventually translate into public health results. "We stand by those predictions," Throckmorton said at a recent public meeting on the drugs. "We're confident in the science, we're confident in the assessments we conducted." Even some former FDA advisers who support expanded use of the drugs say they are only part of the solution. Dr. Lewis Nelson, who previously chaired an FDA panel on drug safety, notes that the drugs don't deter the most common form of abuse: swallowing pills whole. "Certainly, you might not eat one and get high," he said. "You eat three and get high." At least one study found that while OxyContin's reformulation coincided with many abusers switching to other drugs, other users still were able to defeat the pills' technology and snort or inject the contents. David Rook, a 40-year-old Henrico, Virginia, resident who now operates a recovery facility, was among them. Before entering treatment, he said, he would break down abuse-deterrent OxyContins and crush-resistant Opanas using water, lemon juice and a microwave. "The truth is an addict can find a way to abuse a medication one way or the other," he said. A recent HIV outbreak in rural Indiana illustrates the sometimes unpredictable effect of ADFs on abusers' behavior. Approximately 210 people have tested positive for the virus in Scott County since 2014, a public health crisis linked to needle-sharing among abusers of Opana. Endo Pharmaceuticals received approval for a reformulated version of the drug in 2011, making it harder to crush. As a result, many abusers switched from snorting the drug to injecting it with syringes, leading to the spread of the blood-borne HIV virus, according to the state health commissioner and other officials. Endo spokeswoman Heather Zoumas Lubeski declined to comment on the outbreak, but issued a statement saying, "Patient safety has always been a top priority for Endo and we are committed to providing patients with approved products that are safe and effective when used as prescribed." The FDA declined to approve labeling claims for Opana's anti-abuse features, noting that the drug still can easily be cooked and injected. Pfizer, Purdue, Endo and Teva Pharmaceuticals Industries Ltd. spent more than $20 million between 2012 and 2015 on federal lobbying efforts that included support of a bill that would require the FDA to gradually replace current opioids with harder-to-abuse versions that become available. Teva declined comment. Rep. William Keating, D-Mass., first introduced the bill in 2012 and tried again in 2013 and 2015. Like his colleagues at the state level, he employed the hammer-smashing routine to illustrate the medications' crush-resistant properties. Keating said the industry played no part in spurring the bill, even though the head of a nonprofit association funded by abuse-deterrent drugmakers spoke at the press conference introducing his legislation. He also received $2,500 in political contributions from makers of reformulated opioids in 2011 and 2012, a small fraction of his overall fundraising haul. "My interest in this stems from when I was a district attorney and I got to see the lives that were lost," Keating said in an interview. While Keating's bill has not received a vote in Congress, the FDA already has begun moving in the direction suggested by companies, mapping out a process for removing older opioids from the market when newer versions are shown to be more effective at thwarting abuse. "You don't have to pass a bill, necessarily, to change policy," said Dan Cohen of the Abuse Deterrent Coalition, which represents smaller abuse-deterrent manufacturers. The lack of real-world data on reformulated opioids is the main reason some federal officials haven't embraced them. The CDC did not recommend ADFs in its landmark opioid guidelines this year, the first-ever federal recommendations for doctors prescribing the drugs. Why? Frieden, the agency's director, said his staff could not find any evidence showing the updated opioids actually reduce rates of addiction, overdoses or deaths. Center for Public Integrity data reporter Ben Wieder contributed to this article.

Chang H.-Y.,Center for Drug Safety and Effectiveness | Zhou M.,Center for Drug Safety and Effectiveness | Tang W.,George Washington University | Alexander G.C.,Center for Drug Safety and Effectiveness | And 3 more authors.
BMJ (Online) | Year: 2015

Objectives: To determine the real world safety of dabigatran or rivaroxaban compared with warfarin in terms of gastrointestinal bleeding. Design: Retrospective cohort study. Setting: Large administrative database of commercially insured people in United States from 1 October 2010 through 31 March 2012. Participants: Enrollees with a prescription of warfarin, dabigatran, or rivaroxaban between 1 October 2010 and 31 March 2012, who were aged 18 years or older, had continuous enrollment and no oral anticoagulant use during the six months before the entry date, with known age and sex, and with no gastrointestinal bleeding for at least six months before the cohort entry date. The final study sample of 46 163 patients included 4907 using dabigatran, 1649 using rivaroxaban, and 39 607 using warfarin. Main outcome measure: Time to gastrointestinal bleeding. Hazard ratios were derived from Cox proportional hazard models with propensity score weighting and robust estimates of errors. Results: Dabigatran users tended to be older (dabigatran v rivaroxaban v warfarin: 62.0 v 57.6 v 57.4 years) and more likely to be male (69% v 49% v 53%). The rate of gastrointestinal bleeding was highest among dabigatran users and lowest among rivaroxaban users (dabigatran v rivaroxaban v warfarin: 9.01 v 3.41 v 7.02 cases per 100 person years). After adjustment for potentially confounding covariates, there was no evidence of a statistically significant difference in the risk of gastrointestinal bleeding between dabigatran and warfarin users (adjusted hazard ratio 1.21, 95% confidence interval 0.96 to 1.53) or between rivaroxaban and warfarin users (0.98, 0.36 to 2.69). Conclusions: Although rates of gastrointestinal bleeding seem to be similar in this commercially insured sample of adults in the United States, we cannot rule out as much as a 50% increase in the risk of gastrointestinal bleeding with dabigatran compared with warfarin or a more than twofold higher risk of bleeding with rivaroxaban compared with warfarin. © BMJ Publishing Group Ltd 2015.

Barnes G.D.,University of Michigan | Lucas E.,Center for Drug Safety and Effectiveness | Alexander G.C.,Center for Drug Safety and Effectiveness | Goldberger Z.D.,University of Washington
American Journal of Medicine | Year: 2015

Background Four direct oral anticoagulants (DOACs) have been brought to market for the treatment of nonvalvular atrial fibrillation and venous thromboembolism. Many forces, including numerous positive trial results, emerging safety concerns, marketing, and promotion, may shape DOAC adoption by providers. However, relatively little is known regarding their ambulatory utilization compared with warfarin, as well as the degree to which they have decreased under-treatment of atrial fibrillation. Methods We used the IMS Health National Disease and Therapeutic Index, a nationally representative audit of outpatient office visits, to estimate the use of warfarin and DOACs between 2009 and 2014. Results Overall, visits with anticoagulation use increased from 2.05 (95% confidence interval [CI], 1.82-2.27) to 2.83 (95% CI, 2.49-3.17) million (M) quarterly visits (P <.001). Of these, DOAC use has grown to 4.21M (95% CI, 3.63M-4.79M; 38.2% of total) treatment visits in 2014 since their introduction in 2010. Use of all oral anticoagulants in treatment visits for atrial fibrillation has increased from 0.88M (95% CI, 0.74M-1.02M) to 1.72M (95% CI, 1.47M-1.97M; P <.001), with similar DOAC and warfarin use in 2014. Atrial fibrillation visits with anticoagulant use increased from 51.9% (95% CI, 50.4%-53.8%) to 66.9% (95% CI, 65.0%-69.3%) between 2009 and 2014 (P <.001). In 2014, rivaroxaban was the most commonly prescribed DOAC for atrial fibrillation (47.9% of office visits), followed by apixaban (26.5%) and dabigatran (25.5%). Conclusions Direct oral anticoagulants have been adopted rapidly, matching the use of warfarin, and are associated with increased use of oral anticoagulation for patients with atrial fibrillation. © 2015 Elsevier Inc.

Loading Center for Drug Safety and Effectiveness collaborators
Loading Center for Drug Safety and Effectiveness collaborators