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2.
JAMA Intern Med ; 2019 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-31886822

RESUMO

Importance: Extended-release/long-acting (ER/LA) opioids have caused substantial morbidity and mortality in the United States, yet little is known about the efforts of the US Food and Drug Administration (FDA) and drug manufacturers to reduce adverse outcomes associated with inappropriate prescribing or use. This review of 9739 pages of FDA documents obtained through a Freedom of Information Act request aimed to investigate whether the FDA and ER/LA manufacturers were able to assess the effectiveness of the ER/LA Risk Evaluation and Mitigation Strategy (REMS) program by evaluating manufacturer REMS assessments and FDA oversight of these assessments. Observations: The REMS program was implemented largely as planned. The FDA's goal was for 60% of ER/LA prescribers to take REMS-adherent continuing education (CE) between 2012 and 2016; 27.6% (88 316 of 320 000) of prescribers had done so by 2016. Audits of REMS programs indicated close adherence to FDA content guidelines except for financial disclosures. Nonrepresentative cross-sectional surveys of self-selected prescribers suggested modestly greater ER/LA knowledge among CE completers than noncompleters, and claims-based surveillance indicated slowly declining ER/LA prescribing, although the contribution of the REMS to these trends could not be assessed. The effectiveness of the REMS program for reducing adverse outcomes also could not be assessed because the analyses used nonrepresentative samples, lacked adequate controls for confounding, and did not link prescribing or clinical outcomes to prescribers' receipt of CE training. Although the FDA had requested studies tracking adverse outcomes as a function of CE training, the FDA concluded that these studies had not been performed as of the 60-month report in 2017. Conclusions and Relevance: Five years after initiation, the FDA and ER/LA manufacturers could not conclude whether the ER/LA REMS had reduced inappropriate prescribing or improved patient outcomes. Alternative observational study designs would have allowed for more rigorous estimates of the program's effectiveness.

3.
PLoS One ; 14(11): e0225109, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31714946

RESUMO

Despite the importance of pharmacopeial standards, little is known regarding their effect on drug competition. Such information is of particular relevance given the rising costs of prescription drugs and the focus of policy-makers and other stakeholders on addressing these costs. We examined 982 prescription drugs approved by U.S Food and Drug Administration since 1982 to examine the association between U.S. Pharmacopeia (USP) standards, generic entry and prescription costs. The presence of a USP drug product monograph was not associated with the time to the third generic entrant or with the likelihood of having a generic competitor. However, on average, drugs with USP drug product monographs had approximately fifty percent more generic manufacturers in the U.S. than their counterparts after accounting for factors such as market volume, age, route of administration and vintage. This greater competition was associated with an approximate savings of $6.22 billion in 2016, suggesting that USP drug product monographs may play an important role in promoting pharmaceutical competition and reducing prescription drug costs.

4.
Ann Rheum Dis ; 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31672774

RESUMO

OBJECTIVE: To examine whether initiation of interleukin (IL)-17, IL-12/23 or tumour necrosis factor (TNF) inhibitor is associated with an increased risk of serious infection among real-world psoriasis (PsO) or psoriatic arthritis (PsA) patients. METHODS: We assembled a retrospective cohort of commercially insured adults in the USA diagnosed with PsO or PsA between 2015 and 2018. Exposure was dispensation for IL-17 (ixekizumab or secukinumab), IL-12/23 (ustekinumab) or TNF (adalimumab, certolizumab pegol, etanercept, golimumab and infliximab). The outcome was infection requiring hospitalisation after biologic initiation. Incidence rates (IRs) per 100 person-years were computed, and hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression models, adjusted for inverse probability of treatment-weighted propensity scores. RESULTS: A total of 11 560 new treatment episodes were included. Overall, 190 serious infections (2% of treatment episodes) were identified in 9264 person-years of follow-up. Class-specific IRs were similar among IL-17 and TNF, yet significantly lower for IL-12/23. After adjustment for propensity scores, there was no increased risk with IL-17 compared with either TNF (HR=0.89, 95% CI 0.48 to 1.66) or IL-12/23 (HR=1.12, 95% CI 0.62 to 2.03). By contrast, IL-23/23 were associated with a lower risk of infections than TNF (HR=0.59, 95% CI 0.39 to 0.90). CONCLUSIONS: Relative to TNF and IL-17, IL-12/23 inhibitors were associated with a reduced risk of serious infection in biologic-naïve patients with PsO or PsA. In biologic-experienced individuals, there was no difference in infection risk across TNF, IL-17 or IL-12/23 inhibitors.

5.
Mayo Clin Proc ; 94(11): 2220-2229, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31619367

RESUMO

OBJECTIVE: To assess the patterns of angiotensin converting enzyme inhibitors and angiotensin receptor blockers (ACE-I/ARB) discontinuation in the setting of chronic kidney disease (CKD) progression in real-world clinical practice. PATIENTS AND METHODS: We identified incident ACE-I/ARB users with a baseline estimated glomerular filtration rate (eGFR) ≥15 mL/min/1.73 m2 and without end-stage renal disease in the Geisinger Health System between January 1, 2004, and December 31, 2015. We investigated the associations of CKD stage, hospitalizations with and without acute kidney injury (AKI), serum potassium, bicarbonate level, thiazide, and loop diuretic use with ACE-I/ARB discontinuation. RESULTS: Among the 53,912 ACE-I/ARB users, the mean age was 59.9 years, and 50.6% were female. More than half of users discontinued ACE-I/ARB within 5 years of therapy initiation. The risk of ACE-I/ARB discontinuation increased with more advanced CKD stage. For example, patients who initiated ACE-I/ARB with CKD stage G4 (eGFR: 15-29 mL/min/1.73 m2) were 2.09-fold (95% CI, 1.87-2.34) more likely to discontinue therapy than those with eGFR ≥ 90 mL/min/1.73 m2. Potassium level greater than 5.3 mEq/L, systolic blood pressure ≤ 90 mm Hg, bicarbonate level < 22 mmol/L, and intervening hospitalization-particularly AKI-related-were also strong risk factors for ACE-I/ARB discontinuation. Thiazide diuretic use was associated with lower risk, whereas loop diuretic use was associated with higher risk of discontinuation. CONCLUSION: In a real-world cohort, discontinuation of ACE-I/ARB was common, particularly in patients with lower eGFR. Hyperkalemia, hypotension, low bicarbonate level, and hospitalization (AKI-related, in particular) were associated with a higher risk of ACE-I/ARB discontinuation. Additional studies are needed to evaluate the risk-benefit balance of discontinuing ACE-I/ARB in the setting of CKD progression.

6.
Clin J Am Soc Nephrol ; 14(11): 1581-1589, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31582462

RESUMO

BACKGROUND AND OBJECTIVES: Most opioids undergo kidney excretion. The goal of this study was to evaluate opioid-associated risks of death and hospitalization across the range of eGFR. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The study population included adult primary care patients in Geisinger Health (Danville, PA) between 2008 and 2017. People receiving their first opioid prescription were propensity matched to people receiving NSAIDS (and, in sensitivity analysis, gabapentinoids) and the risk of death and hospitalization were compared, classifying opioid medication exposure as time-varying daily oral morphine milligram equivalents (MMEs) across time-varying eGFR. RESULTS: The propensity-matched cohort included 46,246 patients prescribed either opioids or NSAIDs between 2008 and 2017 (mean [SD] age, 54 [16] years; 56% female; 3% of black race). Prescriptions for 1-59 and ≥60 MMEs were associated with higher risk of death (HR, 1.70; 95% CI, 1.41 to 2.05 for 1-59 MMEs; HR, 2.25; 95% CI, 1.82 to 2.79 for ≥60 MMEs) and hospitalization (HR, 1.38; 95% CI, 1.30 to 1.46 for 1-59 MMEs; HR, 1.68; 95% CI, 1.56 to 1.81 for ≥60 MMEs) compared with NSAID prescriptions, when evaluated at eGFR 80 ml/min per 1.73 m2. The relative risk of death associated with ≥60 MMEs was higher at lower GFR (e.g., eGFR, 40 ml/min per 1.73 m2; HR, 3.94; 95% CI, 2.70 to 5.75; P for interaction, 0.01). When gabapentinoids were used as the comparison medication, only ≥60 MMEs were significantly associated with higher risk of death (HR, 2.72; 95% CI, 1.71 to 4.34), although both 1-59 and ≥60 MMEs were associated with risk of hospitalization (HR, 1.22; 95% CI, 1.04 to 1.43 for 1-59 MMEs; HR, 1.54; 95% CI, 1.28 to 1.86 for ≥60 MMEs). CONCLUSIONS: The receipt of prescription opioids was associated with a higher risk of death and hospitalization compared with other pain medications, particularly with higher doses and at lower eGFR.

8.
Am J Health Syst Pharm ; 76(18): 1403-1412, 2019 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-31505561

RESUMO

PURPOSE: Millions of Americans who undergo surgical procedures receive opioid prescriptions as they return home. While some derive great benefit from these medicines, others experience adverse events, convert to chronic opioid use, or have unused medicines that serve as a reservoir for potential nonmedical use. Our aim was to investigate concepts and methods relevant to optimal opioid prescribing and pain treatment in the perioperative period. METHODS: We reviewed existing literature for trials on factors that influence opioid prescribing and optimization of pain treatment for surgical procedures and generated a conceptual framework to guide future quality, safety, and research efforts. RESULTS: Opioid prescribing and pain treatment after discharge from surgery broadly consist of 3 key interacting perspectives, including those of the patient, the perioperative team, and, serving in an essential role for all patients, the pharmacist. Systems-based factors, ranging from the organizational environment's ability to provide multimodal analgesia and participation in enhanced recovery after surgery programs to other healthcare system and macro-level trends, shape these interactions and influence opioid-related safety outcomes. CONCLUSIONS: The severity and persistence of the opioid crisis underscore the urgent need for interventions to improve postoperative prescription opioid use in the United States. Such interventions are likely to be most effective, with the fewest unintended consequences, if based on sound evidence and built on multidisciplinary efforts that include pharmacists, nurses, surgeons, anesthesiologists, and the patient. Future studies have the potential to identify the optimal amount to prescribe, improve patient-focused safety and quality outcomes, and help curb the oversupply of opioids that contributes to the most pressing public health crisis of our time.

9.
Health Serv Res ; 54(5): 1045-1054, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31372990

RESUMO

OBJECTIVE: To estimate the impact of implementing prescription drug monitoring program (PDMP) best practices on prescription opioid use. DATA SOURCES: 2007-2012 Medicare claims for noncancer pain patients, and PDMP attributes from the Prescription Drug Abuse Policy System. STUDY DESIGN: We derived PDMP composite scores using the number of best practices adopted by states (range: 0-14), classifying states as either no PDMP, low strength (0 < score < median), or high strength (score ≥ median). Using generalized linear models, we quantified the association between the PDMP score category and opioid use measures-overall and stratified by disability/age. Sensitivity analyses assessed the general Medicare sample regardless of pain diagnoses, individual PDMP characteristics, and compared GEE model findings to models with state fixed effects. PRINCIPAL FINDINGS: Compared to non-PDMP states, strong PDMP states had lower opioid cumulative doses (-296 mg; 95% CI: -512, -132), days supplied (-7.84; 95% CI: -10.6, -5.04), prescription fill rates (0.97; 95% CI: 0.95, 0.98), and mean daily doses (-2.31 mg; 95% CI: -3.14, -1.48) but greater prevalence of high opioid doses in disabled adults, whereas there was little or no change in older adults. Findings in states with weak PDMPs were substantively similar to those of strong PDMPs. Results from sensitivity analyses were mostly consistent with main findings except there was a null relationship with mean daily doses and high doses in models with state fixed effects. CONCLUSIONS: Comprehensive or minimal adoption of PDMP best practices was associated with mostly comparable effects on Medicare beneficiaries' opioid use; however, these effects were concentrated among nonelderly disabled adults.

10.
Med Care ; 57(9): 667-672, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31404013

RESUMO

BACKGROUND: Although buprenorphine is an evidence-based treatment for opioid use disorder (OUD), it is unknown whether buprenorphine use may affect patients' adherence to treatments for chronic, unrelated conditions. OBJECTIVES: To quantify the effect of buprenorphine treatment on patient adherence to 5 therapeutic classes: (1) antilipids; (2) antipsychotics; (3) antiepileptics; (4) antidiabetics; and (5) antidepressants. RESEARCH DESIGN: This was a retrospective cohort study. SUBJECTS: We started with 12,719 commercially ensured individuals with a diagnosis of OUD and the buprenorphine initiation between January 2011 and June 2015 using Truven Health's MarketScan data. Individuals using any of the 5 therapeutic classes of interest were included. MEASURES: Within the 180-day period post buprenorphine initiation, we derived 2 daily indicators: having buprenorphine and having chronic medication on hand for each therapeutic class of interest. We applied logistic regression to assess the association between these 2 daily indicators, adjusting for demographics, morbidity, and baseline adherence. RESULTS: Across the 5 therapeutic classes, the probability with a given treatment on hand was always higher on days when buprenorphine was on hand. After adjustment for demographics, morbidity, and baseline adherence, buprenorphine was associated with a greater odds of adherence to antilipids [odds ratio (OR), 1.27; 95% confidence interval (CI), 1.04-1.54], antiepileptics (OR, 1.22; CI, 1.10-1.36) and antidepressants (OR, 1.42; CI, 1.32-1.60). CONCLUSIONS: Using buprenorphine to treat OUD may increase adherence to treatments for chronic unrelated conditions, a finding of particular importance given high rates of mental illness and other comorbidities among many individuals with OUD.

11.
JAMA Netw Open ; 2(6): e195388, 2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-31173125

RESUMO

Importance: Despite the increasingly important role of pharmacies in the implementation of naloxone access laws, there is limited information on the impact of such laws at the local level. Objective: To evaluate the availability (with or without a prescription) and cost of naloxone nasal spray at pharmacies in Philadelphia, Pennsylvania, following a statewide standing order enacted in Pennsylvania in August 2015 to allow pharmacies to dispense naloxone without a prescription. Design, Setting, and Participants: A survey study was conducted by telephone of all pharmacies in Philadelphia between February and August 2017. Pharmacies were geocoded and linked with the American Community Survey (2011-2015) to obtain information on the demographic characteristics of census tracts and the Medical Examiner's Office of the Philadelphia Department of Public Health to derive information on the number of opioid overdose deaths per 100 000 people for each planning district. Data were analyzed from March 2018 to February 2019. Main Outcomes and Measures: Availability and out-of-pocket cost of naloxone nasal spray (with or without a prescription) at Philadelphia pharmacies overall and by pharmacy and neighborhood characteristics. Results: Of 454 eligible pharmacies, 418 were surveyed (92.1% response rate). One in 3 pharmacies (34.2%) had naloxone nasal spray in stock; of these, 61.5% indicated it was available without a prescription. There were significant differences in the availability of naloxone by pharmacy type and neighborhood characteristics. Naloxone was both more likely to be in stock (45.9% vs 27.8%; difference, 18.0%; 95% CI, 8.3%-27.8%; P < .001) and available without a prescription (80.6% vs 42.2%; difference, 38.4%; 95% CI, 23.0%-53.8%; P < .001) in chain stores than in independent stores. Naloxone was also less likely to be available in planning districts with very elevated rates of opioid overdose death (≥50 per 100 000 people) compared with those with lower rates (31.1% vs 38.5%). The median (interquartile range) out-of-pocket cost among pharmacies offering naloxone without a prescription was $145 ($119-$150); costs were greatest in independent pharmacies and planning districts with elevated rates of opioid overdose death. Conclusions and Relevance: Despite the implementation of a statewide standing order in Pennsylvania more than 3 years prior to this study, only one-third of Philadelphia pharmacies carried naloxone nasal spray and many also required a physician's prescription. Efforts to strengthen the implementation of naloxone access laws and better ensure naloxone supply at local pharmacies are warranted, especially in localities with the highest rates of overdose death.

13.
Prev Med ; 126: 105744, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31173803

RESUMO

There was an increase in the number and coverage of state and local clean indoor air laws in the US during the past fifteen years. These laws coincided with increases in federal, state, and local cigarette excise taxes. In light of these changes, the objective of this study was to examine the association between clean indoor air laws, cigarette excise taxes and smoking patterns between 2003 and 2011. Using data on 62,165 adult participants in the 2003 and 2010/2011 Current Population Survey-Tobacco Use Supplement who reported smoking cigarettes in the past year, we examined the association of state and county workplace, bar, and restaurant clean indoor air laws and cigarette excise taxes with quitting and current every-day smoking. Between 2003 and 2011, quitting increased and daily smoking among those who continued to smoke decreased significantly. Participants living in states and counties with higher excise taxes and more comprehensive clean indoor air laws had a higher likelihood of quitting and lower likelihood of everyday smoking. Based on the assumption of no uncontrolled confounding, changes in taxes and laws accounted for 64.8% of the increase in smoking cessation and all of the reduction in everyday smoking. Implementation of state and county-level clean indoor air laws and cigarette taxes appears to have achieved the intended goal of encouraging smokers to either quit or reduce their frequency of smoking.

14.
JAMA Netw Open ; 2(4): e192606, 2019 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-31002324

RESUMO

Importance: It is unknown whether and how pharmacy closures alter medication adherence. Objective: To examine the association between pharmacy closures and adherence to statins, ß-blockers, and oral anticoagulants among adults 50 years or older in the United States. Design, Setting, and Participants: In this retrospective cohort study, comparative interrupted time series analyses were performed using a nationally representative 5% random sample of anonymized, longitudinal, individual-level pharmacy claims from IQVIA LRx LifeLink. Analyses included all prescription claims for individuals followed up between January 1, 2011, and December 31, 2016. Separate cohorts were derived for users of statins, ß-blockers, and oral anticoagulants. The differential association of pharmacy closure was examined as a function of baseline adherence, pharmacy, and individual characteristics. Main Outcomes and Measures: Difference in monthly adherence, measured as proportion of days covered, during 12-month baseline and follow-up periods among patients using a pharmacy that subsequently closed (closure cohort) compared with their counterparts (control cohort). Results: Among 3 089 803 individuals filling at least 1 statin prescription between January 1, 2011, and December 31, 2016 (mean [SD] age, 66.3 [9.3] years; 52.0% female), 3.0% (n = 92 287) filled at a pharmacy that subsequently closed. Before closure, monthly adherence was similar in the closure and control cohorts (mean [SD], 70.5% [26.7%] vs 70.7% [26.5%]). In multivariable models, individuals filling at pharmacies that closed experienced an immediate and significant decline (on average, an absolute change of -5.90%; 95% CI, -6.12% to -5.69%) in statin adherence during the first 3 months after closure compared with their counterparts. This difference persisted over 12 months of follow-up. A similar decline in adherence was observed when examining cohorts using ß-blockers (-5.71%; 95% CI, -5.96% to -5.46%) or oral anticoagulants (-5.63%; 95% CI, -6.24% to -5.01%). The mean association of pharmacy closure with adherence was greater among individuals using independent pharmacies (-7.89%; 95% CI, -8.32% to -7.47%) or living in neighborhoods with fewer pharmacies (-7.98%; 95% CI, -8.50% to -7.47%) compared with their counterparts. Conclusions and Relevance: Pharmacy closures are associated with persistent, clinically significant declines in adherence to cardiovascular medications among older adults in the United States. Efforts to reduce nonadherence to prescription medications should consider the role of pharmacy closures, especially among patients at highest risk.

15.
Am J Surg ; 218(5): 818-827, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31023548

RESUMO

BACKGROUND: The consequences of opioids-including post-surgical prescriptions-remain a critical public health issue. We sought to determine how procedure type and subspecialty group influence new opioid use after procedures. METHODS: We analyzed 2011-2015 IBM MarketScan Research Databases to identify opioid-naïve adults prescribed opioids for single surgical procedures. We defined new opioid continuation (primary outcome) a priori as receipt of prescription opioids between 90 and 180 days after the procedure. RESULTS: Among 912,882 individuals, new opioid continuation was higher for non-operating room compared to operating room procedures (13.1% versus 9.2%; aOR 1.61; 95% CI 1.59-1.64) and higher for subspecialties including colorectal surgery (aOR 1.35; 95% CI 1.26-1.43) and cardiovascular surgery (aOR 1.30; 95% CI 1.12-1.50) compared to urology as a referent. New opioid continuation was also associated with perioperative opioid prescription dosage, days' supply, preoperative receipt, and multiple prescriptions. CONCLUSIONS: Opioids prescriptions associated with non-operating room surgical exposures appear to confer higher risk regarding conversion to new long-term opioid use.

16.
Pain Med ; 2019 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-30865779

RESUMO

OBJECTIVE: To describe current state-level policies in the United States, January 1, 2007-June 1, 2017, limiting high morphine equivalent daily dose (MEDD) prescribing. METHODS: State-level MEDD threshold policies were reviewed using LexisNexis and Westlaw Next for legislative acts and using Google for nonlegislative state-level policies. The websites of each state's Medicaid agency, health department, prescription drug monitoring program, workers' compensation board, medical board, and pharmacy board were reviewed to identify additional policies. The final policy list was checked against existing policy compilations and academic literature and through contact with state health agency representatives. Policies were independently double-coded on the categories: state, agency/organization, policy type, effective date, threshold level, and policy exceptions. RESULTS: Currently, 22 states have at least one type of MEDD policy, most commonly guidelines (14 states), followed by prior authorizations (four states), rules/regulations (four states), legislative acts (three states), claim denials (two states), and alert systems/automatic patient reports (two states). Thresholds range widely (30-300 mg MEDD), with higher thresholds generally corresponding to more restrictive policies (e.g., claim denial) and lower thresholds corresponding to less restrictive policies (e.g., guidelines). The majority of policies exclude some groups of opioid users, most commonly patients with terminal illnesses or acute pain. CONCLUSIONS: MEDD policies have gained popularity in recent years, but considerable variation in threshold levels and policy structure point to a lack of consensus. This work provides a foundation for future evaluation of MEDD policies and may inform states considering adopting such policies.

17.
Clin Trials ; 16(3): 329-333, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30922113

RESUMO

BACKGROUND/AIMS: Despite the increasing globalization of clinical trials, little is known regarding how the trial site costs vary around the world. We quantified the geographical distribution and regional cost differences for the clinical trials that established the benefits for new therapeutic drugs approved by the US Food and Drug Administration in 2015 and 2016. METHODS: We included all pivotal clinical trials for 59 new molecular entities approved by the US Food and Drug Administration in 2015 and 2016 that included at least one site in North America. We derived cost estimates from IQVIA's CostPro, a global clinical trial cost-estimating tool used by pharmaceutical sponsors. We assessed the patient and site allocation of these trials across eight geographic regions. To quantify the region-specific cost differences, we conducted a within-trial comparison by expressing the estimated regional costs associated with the sites in each global region as a percent of the same costs in North America. We also estimated the percentage breakdown of regional cost components (pass-through, site management, regulatory, and study conduct costs) for each trial and for all endpoints reported the median and interquartile range. RESULTS: Overall, 127 pivotal clinical trials enrolled 91,415 patients from 13,264 sites. Most patients (60.3%) and sites (57.3%) were outside North America. A median of 66% of the total estimated trial costs (interquartile range: 60%-72%) were spent on regional tasks, with the largest share (53.3%) going directly to trial sites and the remainder going to other regional trial management tasks. Differences were greatest in four lower cost regions: Africa, with an estimated regional cost per site of 49% of North America (interquartile range: 44%-56%), Central Europe 50% (interquartile range: 41%-63%), Middle East 53% (interquartile range: 42%-64%) and Latin America 59% (interquartile range: 50%-70%). Overall, 90 (71%) of the 127 pivotal trials had a total of 3160 sites in these lower cost regions. In contrast, savings were more limited in Western Europe, Oceania, and Asia, where estimated regional costs were 78% of North America (interquartile range: 67%-89%). One-quarter of the trials with sites in Asia and Oceana did not achieve cost savings in those regions relative to North America. CONCLUSION: Among this sample of pivotal trials for recently approved US Food and Drug Administration products, most patients and sites enrolled were outside of North America, with selection of regional sites having a significant impact on total trial costs.

18.
Drug Alcohol Depend ; 197: 141-148, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30825794

RESUMO

BACKGROUND: Pain is more common among people living with HIV (PLWH) than their counterparts; however, it is unclear whether analgesic use differs by HIV status. METHODS: We analyzed Medicaid pharmacy claims from adults in 14 US states from 2001 to 2009 to identify opioid and non-opioid analgesic prescriptions and compared prescribing trends by HIV status. We accounted for clinical and demographic differences by using inverse probability weights and by restricting the sample to a subgroup with a common comorbidity, diabetes, chosen for its high prevalence and association with lifestyle and chronic pain. We estimated the incidence of chronic opioid therapy (COT) (≥90 consecutive days with an opioid prescription) among opioid-naïve individuals. RESULTS: Rates of opioid and non-opioid use increased approximately two-fold from 2001 to 2009. PLWH received approximately twice as many prescriptions as those without HIV. In an unadjusted Cox regression, PLWH were three times more likely to receive COT compared to those without HIV (hazard ratio (HR) = 3.06, 95% CI 2.76-3.39). When restricting to patients with diabetes and adjusting for age, sex, state, comorbidity score, depression, bipolar disorder, and schizophrenia, the HR decreased to 1.26 (95% CI 0.97-1.63). CONCLUSIONS: Higher opioid use among PLWH was largely a function of patients' demographic characteristics and health status. The high incidence of COT among PLWH underscores the importance of practice guidelines that minimize adverse events associated with opioid use.


Assuntos
Analgésicos Opioides/uso terapêutico , Prescrições de Medicamentos , Infecções por HIV/epidemiologia , Medicaid/tendências , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Adolescente , Adulto , Idoso , Analgésicos Opioides/efeitos adversos , Dor Crônica/tratamento farmacológico , Dor Crônica/epidemiologia , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Relacionados ao Uso de Opioides/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Estados Unidos/epidemiologia , Adulto Jovem
19.
Clin Pharmacol Drug Dev ; 8(7): 914-921, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30707505

RESUMO

Biologics, especially monoclonal antibodies, are increasingly important in the pharmaceutical marketplace. Population pharmacokinetic (PK) analyses could be useful to guide the need for dose adjustments among special populations, yet it is unknown how commonly such analyses are performed during biologics development. We summarized the characteristics of population PK models of biologics and examined their role in informing the drug labels. To do so, we extracted relevant characteristics of 86 biologics approved by the U.S. Food and Drug Administration's Center for Drug Evaluation and Research between 2003 and 2017. Ninety-four percent of monoclonal antibodies (51 of 54 biologics), 75% of fusion proteins with Fc receptor (6 of 8 biologics), and 33% of other proteins (8 of 24 biologics) included population PK analyses. Of these analyses, approximately half (45%) used a 2-compartment model with linear clearance as the base model structure. Body size was the most frequently included covariate in the final models (included in 94% of the 64 biologics in which covariate analysis was performed), although age (11%), sex (35%), race (26%), and renal function (27%) were also included in some models. In 70% to 90% of cases in which the effect of these covariates was examined, information regarding the effect of these on PK was included in the label. These results suggest that population PK analyses provide important information about the impact of intrinsic factors on the PK in the label of biologics by the U.S. Food and Drug Administration.

20.
J Am Geriatr Soc ; 67(5): 1066-1073, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30703251

RESUMO

BACKGROUND/OBJECTIVES: The treatment of type 2 diabetes in older adults requires special considerations including avoidance of hypoglycemia, yet variation in diabetes treatment with aging is not well understood. In this study, we compared nationally representative diabetes treatment patterns and trends between older adults (≥65 y) and younger adults (30-64 y). DESIGN: Repeated cross-sectional physician surveys from 2006 to 2015. SETTING: The National Ambulatory Medical Care Survey, an annual probability sample of visits to office-based US physicians. PARTICIPANTS: Adults with type 2 diabetes using one or more diabetes medications. MEASUREMENTS: Proportions of visits in which patients treated with each diabetes medication class were compared between older and younger adults in 2-year intervals. RESULTS: From 2006 to 2015, the average number of yearly visits for older and younger adults was 25.4 million and 24.2 million, respectively. In 2014-2015, visits for older compared with younger adults involved less use of metformin (56.0% vs 70.0%; p < .001) and glucagon-like peptide 1 receptor agonists (2.9% vs 6.2%; p = .004), and more use of long-acting insulin (30.2% vs 22.4%; p = .017); other classes were used similarly. During the study period, long-acting insulin use increased markedly in older adults, particularly between 2010 and 2015 where it rose from 12.5% to 30.2% of visits (P-trend <.001). In younger adult visits, long-acting insulin use increased modestly (17.2% to 22.4%) and at a slower rate compared with older adult visits (p < .001). CONCLUSION: The ambulatory treatment of type 2 diabetes differs between older and younger adults, with the treatment of older adults characterized by low use of newer diabetes medications and a greater and rapidly increasing use of long-acting insulin. These findings call for further research clarifying the comparative effectiveness and safety of newer diabetes medications and long-acting insulin to optimize diabetes care for older patients. J Am Geriatr Soc 67:1066-1073, 2019.

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