Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 227
Filtrar
1.
Drug Saf ; 2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33904111

RESUMO

INTRODUCTION: Since 2007, the US Food and Drug Administration has had the authority to require risk evaluation and mitigation strategy (REMS) programs for certain medications with serious safety concerns to help ensure the benefits of the medication outweigh its risks. Such programs can include requirements for patient monitoring, restrictions on dispensing or administration, and physician and pharmacy training and certification. However, there has been only scattered evidence on the impact of REMS programs on informed decision making, medication access, or patient outcomes. OBJECTIVE: The objective of this article was to describe a study that researchers at Brigham and Women's Hospital and Harvard Medical School will conduct in partnership with the Food and Drug Administration's Office of Surveillance and Epidemiology to investigate systematically how REMS programs have operated in practice. METHODS: Investigations include health insurance claims-based analyses to understand patterns of drug use, adherence to safety requirements, and patient outcomes under REMS programs; surveys and interviews to understand physician and patient experiences with REMS; and REMS program material-based and interview-based analyses to understand the effectiveness of risk communication in REMS programs. CONCLUSIONS: These research activities will evaluate the performance of REMS programs, provide information on the benefits and burdens to patients and healthcare providers, and generate recommendations for actionable steps to improve REMS programs overall.

2.
Pharmacoepidemiol Drug Saf ; 30(6): 671-684, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33715267

RESUMO

PURPOSE: Consensus is needed on conceptual foundations, terminology and relationships among the various self-controlled "trigger" study designs that control for time-invariant confounding factors and target the association between transient exposures (potential triggers) and abrupt outcomes. The International Society for Pharmacoepidemiology (ISPE) funded a working group of ISPE members to develop guidance material for the application and reporting of self-controlled study designs, similar to Standards of Reporting Observational Epidemiology (STROBE). This first paper focuses on navigation between the types of self-controlled designs to permit a foundational understanding with guiding principles. METHODS: We leveraged a systematic review of applications of these designs, that we term Self-controlled Crossover Observational PharmacoEpidemiologic (SCOPE) studies. Starting from first principles and using case examples, we reviewed outcome-anchored (case-crossover [CCO], case-time control [CTC], case-case-time control [CCTC]) and exposure-anchored (self-controlled case-series [SCCS]) study designs. RESULTS: Key methodological features related to exposure, outcome and time-related concerns were clarified, and a common language and worksheet to facilitate the design of SCOPE studies is introduced. CONCLUSIONS: Consensus on conceptual foundations, terminology and relationships among SCOPE designs will facilitate understanding and critical appraisal of published studies, as well as help in the design, analysis and review of new SCOPE studies. This manuscript is endorsed by ISPE.

3.
Am J Epidemiol ; 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33615330

RESUMO

Tree-based scan statistics (TreeScan) are a data-mining method that adjusts for multiple testing of correlated hypotheses when screening thousands of potential adverse events for signal identification. Simulation has demonstrated the promise of TreeScan with a propensity score (PS) matched cohort design. However, it is unclear which variables to include in a PS for applied signal identification studies to simultaneously adjust for confounding across potential outcomes. We selected 4 drug pairs with well understood safety profiles. For each pair, we evaluated 5 candidate PSs with different combinations of: predefined general covariates (comorbidity, frailty, utilization), empirically-selected (data driven) covariates, and covariates tailored to the drug pair. For each pair, statistical alerting patterns were similar with alternative PSs (≤11 alerts in 7,996 outcomes scanned). Including covariates tailored to exposure did not appreciably impact screening results. Including empirically-selected covariates can provide better proxy coverage for confounders but can also decrease power. Unlike tailored covariates, empirical and predefined general covariates can be applied "out of the box" for signal identification. The choice of PS depends on level of concern about residual confounding versus loss of power. Potential signals should be followed by pharmacoepidemiologic assessment where confounding control is tailored to the specific outcome(s) under investigation.

4.
Am Heart J ; 233: 109-121, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33358690

RESUMO

BACKGROUND: In patients with atrial fibrillation, incomplete adherence to anticoagulants increases risk of stroke. Non-warfarin oral anticoagulants (NOACs) are expensive; we evaluated whether higher copayments are associated with lower NOAC adherence. METHODS: Using a national claims database of commercially-insured patients, we performed a cohort study of patients with atrial fibrillation who newly initiated a NOAC from 2012 to 2018. Patients were stratified into low (<$35), medium ($35-$59), or high (≥$60) copayments and propensity-score weighted based on demographics, insurance characteristics, comorbidities, prior health care utilization, calendar year, and the NOAC received. Follow-up was 1 year, with censoring for switching to a different anticoagulant, undergoing an ablation procedure, disenrolling from the insurance plan, or death. The primary outcome was adherence, measured by proportion of days covered (PDC). Secondary outcomes included NOAC discontinuation (no refill for 30 days after the end of NOAC supply) and switching anticoagulants. We compared PDC using a Kruskal-Wallis test and rates of discontinuation and switching using Cox proportional hazards models. RESULTS: After weighting patients across the 3 copayment groups, the effective sample size was 17,558 patients, with balance across 50 clinical and demographic covariates (standardized differences <0.1). Mean age was 62 years, 29% of patients were female, and apixaban (43%), and rivaroxaban (38%) were the most common NOACs. Higher copayments were associated with lower adherence (P < .001), with a PDC of 0.82 (Interquartile range [IQR] 0.36-0.98) among those with high copayments, 0.85 (IQR 0.41-0.98) among those with medium copayments, and 0.88 (IQR 0.41-0.99) among those with low copayments. Compared to patients with low copayments, patients with high copayments had higher rates of discontinuation (hazard ratio [HR] 1.13, 95% confidence interval [CI] 1.08-1.19; P < .001). CONCLUSIONS: Among atrial fibrillation patients newly initiating NOACs, higher copayments in commercial insurance were associated with lower adherence and higher rates of discontinuation in the first year. Policies to lower or limit cost-sharing of important medications may lead to improved adherence and better outcomes among patients receiving NOACs.


Assuntos
Fibrilação Atrial/complicações , Dedutíveis e Cosseguros/economia , Adesão à Medicação/estatística & dados numéricos , Acidente Vascular Cerebral/prevenção & controle , Anticoagulantes/economia , Anticoagulantes/uso terapêutico , Antitrombinas/economia , Antitrombinas/uso terapêutico , Estudos de Coortes , Dabigatrana/economia , Dabigatrana/uso terapêutico , Bases de Dados Factuais/estatística & dados numéricos , Dedutíveis e Cosseguros/estatística & dados numéricos , Custos de Medicamentos , Inibidores do Fator Xa/economia , Inibidores do Fator Xa/uso terapêutico , Feminino , Humanos , Masculino , Medicare Part C/estatística & dados numéricos , Pessoa de Meia-Idade , Pirazóis/economia , Pirazóis/uso terapêutico , Piridinas/economia , Piridinas/uso terapêutico , Piridonas/economia , Piridonas/uso terapêutico , Rivaroxabana/economia , Rivaroxabana/uso terapêutico , Tamanho da Amostra , Acidente Vascular Cerebral/etiologia , Tiazóis/economia , Tiazóis/uso terapêutico , Estados Unidos , Varfarina/economia , Varfarina/uso terapêutico
5.
Drug Saf ; 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33206339

RESUMO

INTRODUCTION: Risk evaluation and mitigation strategy (REMS) programs are intended to improve safe use of US Food and Drug Administration-approved drugs. However, controversy exists over whether they consistently accomplish this goal. OBJECTIVE: We aimed to assess how initiation of the erythropoiesis stimulating agents (ESAs) darbepoetin alfa and epoetin alfa changed following implementation and enforcement (following a 1-year post-implementation grace period) of a prominent REMS program warning physicians against use in cancer patients with hemoglobin above 10 g/dL. METHODS: Using claims data from a large US commercial insurance company, we conducted interrupted time-series analyses of darbepoetin alfa and epoetin alfa initiation among adult cancer patients in the 12 months before REMS program implementation, after REMS program implementation, and after REMS program enforcement. We also evaluated differences in inappropriate initiation (hemoglobin tests all above 10 g/dL in the prior month) between the periods. RESULTS: In total, we identified 3456 darbepoetin alfa initiators and 2632 epoetin alfa initiators. Over the study period, the monthly number of initiators per 100,000 patients with cancer fell from 119 to 32 for darbepoetin alfa and from 82 to 34 for epoetin alfa. However, non-significant post-REMS program implementation level and slope changes per 100,000 adult patients with cancer were observed for darbepoetin alfa (level 0.03 [95% confidence interval (CI) -14.98 to 15.05]; slope 1.94 [95% CI -0.22 to 4.10]) and epoetin alfa (level -4.10 [95% CI -16.85 to 8.65]; slope -0.52 [95% CI -2.35 to 1.32]). Non-significant post-REMS program enforcement level and slope changes were also seen for both drugs (darbepoetin alfa level 1.58 [95% CI -0.58 to 3.74, slope -0.28 [95% CI -15.29 to 14.73]; epoetin alfa level 1.58 (95% CI -0.26 to 3.42], slope 5.74 [95% CI -7.01 to 18.49]). Finally, non-significant changes in inappropriate darbepoetin alfa (60% vs. 53% vs. 57%, p = 0.68) and epoetin alfa (53% vs. 53% vs. 46%, p = 0.41) initiation were observed between the three study periods. CONCLUSION: REMS program implementation and enforcement were not associated with significant changes in ESA initiation, adding to concerns over the degree to which certain REMS programs enhance patient safety.

7.
Drugs ; 80(18): 1961-1972, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33151482

RESUMO

BACKGROUND: Treatment decisions for Coronavirus Disease 2019 (COVID-19) depend on disease severity, but the prescribing pattern by severity and drivers of therapeutic choices remain unclear. OBJECTIVES: The objectives of the study were to evaluate pharmacological treatment patterns by COVID-19 severity and identify the determinants of prescribing for COVID-19. METHODS: Using electronic health record data from a large Massachusetts-based healthcare system, we identified all patients aged ≥ 18 years hospitalized with laboratory-confirmed COVID-19 from 1 March to 24 May, 2020. We defined five levels of COVID-19 severity at hospital admission: (1) hospitalized but not requiring supplemental oxygen; (2-4) hospitalized and requiring oxygen ≤ 2, 3-4, and ≥ 5 L per minute, respectively; and (5) intubated or admitted to an intensive care unit. We assessed the medications used to treat COVID-19 or as supportive care during hospitalization. RESULTS: Among 2821 patients hospitalized for COVID-19, we found inpatient mortality increased by severity from 5% for level 1 to 23% for level 5. As compared to patients with severity level 1, those with severity level 5 were 3.53 times (95% confidence interval 2.73-4.57) more likely to receive a medication used to treat COVID-19. Other predictors of treatment were fever, low oxygen saturation, presence of co-morbidities, and elevated inflammatory biomarkers. The use of most COVID-19 relevant medications has dropped substantially while the use of remdesivir and therapeutic anticoagulants has increased over the study period. CONCLUSIONS: Careful consideration of disease severity and other determinants of COVID-19 drug use is necessary for appropriate conduct and interpretation of non-randomized studies evaluating outcomes of COVID-19 treatments.

8.
Clin Pharmacol Ther ; 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33245789

RESUMO

Self-controlled designs, specifically the case-crossover (CCO) and the self-controlled case series (SCCS), are increasingly utilized to generate real-world evidence (RWE) on drug-drug interactions (DDIs). While these designs share the advantages and limitations of within-individual comparison, they also have design-specific assumptions. It is not known to what extent the differences in assumptions lead to different results in RWE DDI analyses. Using a nationwide US commercial healthcare insurance database (2006-2016), we compared the CCO and SCCS designs, as they are implemented in DDI studies, within 5 DDI-outcome examples: (1) simvastatin + clarithromycin and muscle-related toxicity; (2) atorvastatin + valsartan, and muscle-related toxicity; and (3-5) dabigatran + P-glycoprotein inhibitor (clarithromycin, amiodarone, verapamil) and bleeding. Analyses were conducted within person-time exposed to the object drug (statins and dabigatran) and adjusted for bias associated with the inhibiting drugs via control groups of individuals unexposed to the object drug. The designs yielded similar estimates in most examples, with SCCS displaying better statistical efficiency. With both designs, results varied across sensitivity analyses, particularly in CCO analyses with small number of exposed individuals. Analyses in controls revealed substantial bias that may be differential across DDI-exposed and control individuals. Thus, both designs showed no association between amiodarone or verapamil and bleeding in dabigatran-exposed but revealed strong positive associations in controls. Overall, bias adjustment via a control group had a larger impact on results than the choice of a design, highlighting the importance and challenges of appropriate control group selection for adequate bias control in self-controlled analyses of DDIs.

9.
Artigo em Inglês | MEDLINE | ID: mdl-33099844

RESUMO

PURPOSES: Drug induced acute liver injury (ALI) is a frequent cause of liver failure. Case-based designs were empirically assessed and calibrated in the French National claims database (SNDS), aiming to identify the optimum design for drug safety alert generation associated with ALI. METHODS: All cases of ALI were extracted from SNDS (2009-2014) using specific and sensitive definitions. Positive and negative drug controls were used to compare 196 self-controlled case series (SCCS), case-control (CC), and case-population (CP) design variants, using area under the receiver operating curve (AUC), mean square error (MSE) and coverage probability. Parameters that had major impacts on results were identified through logistic regression. RESULTS: Using a specific ALI definition, AUCs ranged from 0.78 to 0.94, 0.64 to 0.92 and 0.48 to 0.85, for SCCS, CC and CP, respectively. MSE ranged from 0.12 to 0.40, 0.22 to 0.39 and 1.03 to 5.29, respectively. Variants adjusting for multiple drug use had higher coverage probabilities. Univariate regressions showed that high AUCs were achieved with SCCS using exposed time as the risk window. The top SCCS variant yielded an AUC = 0.93 and MSE = 0.22 and coverage = 86%, with 1/7 negative and 13/18 positive controls presenting significant estimates. CONCLUSIONS: SCCS adjusting for multiple drugs and using exposed time as the risk window performed best in generating ALI-related drug safety alert and providing estimates of the magnitude of the risk. This approach may be useful for ad-hoc pharmacoepidemiology studies to support regulatory actions.

10.
JAMA Intern Med ; 2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32897307

RESUMO

Importance: Previous observational studies have suggested that fluoroquinolones are associated with aortic aneurysm or dissection, but these studies may be subject to confounding by indication or surveillance bias. Objective: To assess the association of fluoroquinolones with risk of aortic aneurysm or aortic dissection (AA/AD) while accounting for potential confounding by fluoroquinolone indication and bias owing to differential surveillance. Design, Setting, and Participants: In an observational cohort study using a US commercial claims database, 2 pairwise 1:1 propensity score-matched cohorts were identified: patients aged 50 years or older with a diagnosis of pneumonia 3 days or less before initiating treatment with a fluoroquinolone or azithromycin and patients aged 50 years or older with a urinary tract infection (UTI) diagnosis 3 days or less before initiating a fluoroquinolone or combined trimethoprim and sulfamethoxazole. Hazard ratios (HRs) and 95% CIs were estimated controlling for 85 baseline confounders. In a secondary analysis, patients receiving fluoroquinolones were compared with those receiving amoxicillin, both with and without considering baseline aortic imaging, to address differences in detection of AA/AD before antibiotic use. Data on patients within the database from January 1, 2003, through September 30, 2015, were analyzed. Data analysis was conducted from July 23, 2019, to July 6, 2020. Main Outcomes and Measures: Hospitalization for AA/AD occurring within 60 days following treatment initiation. Results: After propensity score matching, patient characteristics were well balanced, with 279 554 patients (mean [SD] age, 63.66 [10.93] years; 149 976 women [53.6%]) in the pneumonia cohort and 948 364 patients (mean [SD] age, 62.06 [10.33] years; 823 667 women [86.9%]) in the UTI cohort. Initiators of fluoroquinolones (n = 139 772 pairs in the pneumonia cohort and n = 474 182 pairs in the UTI cohort) had an increased rate of AA/AD compared with initiators of azithromycin (HR, 2.57; 95% CI, 1.36-4.86; incidence, 0.03% for fluoroquinolones vs 0.01% for azithromycin) but no increased rate compared with initiators of combined trimethoprim and sulfamethoxazole (HR, 0.99; 95% CI, 0.62-1.57; incidence, <0.01% in both UTI groups). Secondary analysis using amoxicillin as a comparator (n = 3 976 162 pairs) produced results consistent with those from earlier studies (HR, 1.54; 95% CI, 1.33-1.79; incidence, <0.01% in both groups). Requiring baseline imaging in this cohort (n = 542 649 pairs) to address surveillance bias attenuated the increased rate (HR, 1.13; 95% CI, 0.96-1.33; incidence, 0.06% for fluoroquinolones vs 0.05% for amoxicillin). Conclusions and Relevance: The findings of this nationwide cohort study of adults with pneumonia or UTI suggest an increased relative rate of AA/AD associated with fluoroquinolones within the pneumonia cohort but not within the UTI cohort. In both cohorts, the absolute rate of AA/AD appeared to be low (<0.1%). The increased relative rate observed in the pneumonia cohort may be due to residual confounding or surveillance bias.

11.
Epidemiology ; 31(6): 860-871, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32897909

RESUMO

BACKGROUND: We examined whether the apparent association between renal cell carcinoma (RCC) and use of dihydropyridine calcium channel blockers (CCBs) was explained by confounding by indication since hypertension, the main indication for CCBs, is a risk factor for RCC. METHODS: Using Danish health registries, we conducted a nested case-control study including 7315 RCC cases during 2000-2015. We matched each case with up to 20 controls on age and sex using risk-set sampling. We estimated odds ratios (ORs) for long-term CCB use associated with RCC using conditional logistic regression. We addressed confounding by indication by (1) adjusting for hypertension severity indicators; (2) evaluating dose-response patterns; (3) examining whether other first-line anti-hypertensives were associated with RCC; and (4) using an active comparator new user design by nesting the study in new users of CCBs or angiotensin-converting enzyme inhibitors (ACEIs). RESULTS: The adjusted OR for RCC associated with long-term CCB use compared to non-use was 1.76 (1.63-1.90). After we additionally adjusted for hypertension severity indicators, the OR remained elevated (OR 1.37; confidence interval [CI] 1.25, 1.49) with evidence of a dose-response pattern. Other anti-hypertensives were also associated with RCC, for example, ACEIs (OR 1.27; 95% CI = 1.16, 1.39) and thiazides (OR 1.22; 95% CI = 1.12, 1.34). In the active comparator new user design, the OR was 1.21 (95% CI = 0.95, 1.53) for use of CCBs compared with ACEIs. CONCLUSIONS: In this population, confounding by indication appeared to explain at least part of the association between RCC and dihydropyridine CCBs.

12.
PLoS One ; 15(9): e0227783, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32925977

RESUMO

PURPOSE: To quantify differences in the age, gender, race, and clinical complexity of Medicare beneficiaries treated by ophthalmologists and optometrists in each of the United States. DESIGN: Cross-sectional study based on publicly accessible Medicare payment and utilization data from 2012 through 2017. METHODS: For each ophthalmic and optometric provider, demographic information of treated Medicare beneficiaries was obtained from the Medicare Provider Utilization and Payment Data from the Centers for Medicare and Medicaid Services (CMS) for the years 2012 through 2017. Clinical complexity was defined using CMS Hierarchical Condition Category (HCC) coding. RESULTS: From 2012 through 2017, ophthalmologists in every state treated statistically significantly older beneficiaries, with the greatest difference (4.99 years in 2014) between provider groups seen in Rhode Island. In most states there was no gender difference among patients treated by the providers but in 46 states ophthalmologists saw a more racially diverse group of beneficiaries. HCC risk score analysis demonstrated that ophthalmologists in all 50 states saw more medically complex beneficiaries and the differences were statistically significant in 47 states throughout all six years. CONCLUSIONS: Although there are regional variations in the characteristics of patients treated by ophthalmologists and optometrists, ophthalmologists throughout the United States manage older, more racially diverse, and more medically complex Medicare beneficiaries.


Assuntos
Oftalmopatias/terapia , Medicare/estatística & dados numéricos , Oftalmologia/estatística & dados numéricos , Optometria/estatística & dados numéricos , Demandas Administrativas em Assistência à Saúde/estatística & dados numéricos , Fatores Etários , Idoso , Grupos de Populações Continentais/estatística & dados numéricos , Estudos Transversais , Oftalmopatias/diagnóstico , Oftalmopatias/economia , Feminino , Humanos , Masculino , Medicare/economia , Oftalmologistas/economia , Oftalmologistas/estatística & dados numéricos , Oftalmologia/economia , Optometristas/economia , Optometristas/estatística & dados numéricos , Optometria/economia , Padrões de Prática Médica/economia , Fatores Sexuais , Estados Unidos
13.
Ophthalmology ; 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32777229

RESUMO

PURPOSE: There is an urgent need for treatments that prevent or delay development to advanced age-related macular degeneration (AMD). Drugs already on the market for other conditions could affect progression to neovascular AMD (nAMD). If identified, these drugs could provide insights for drug development targets. The objective of this study was to use a novel data mining method that can simultaneously evaluate thousands of correlated hypotheses, while adjusting for multiple testing, to screen for associations between drugs and delayed progression to nAMD. DESIGN: We applied a nested case-control study to administrative insurance claims data to identify cases with nAMD and risk-set sampled controls that were 1:4 variable ratio matched on age, gender, and recent healthcare use. PARTICIPANTS: The study population included cases with nAMD and risk set matched controls. METHODS: We used a tree-based scanning method to evaluate associations between hierarchical classifications of drugs that patients were exposed to within 6 months, 7 to 24 months, or ever before their index date. The index date was the date of first nAMD diagnosis in cases. Risk-set sampled controls were assigned the same index date as the case to which they were matched. The study was implemented using Medicare data from New Jersey and Pennsylvania, and national data from IBM MarketScan Research Database. We set an a priori threshold for statistical alerting at P ≤ 0.01 and focused on associations with large magnitude (relative risks ≥ 2.0). MAIN OUTCOME MEASURES: Progression to nAMD. RESULTS: Of approximately 4000 generic drugs and drug classes evaluated, the method detected 19 distinct drug exposures with statistically significant, large relative risks indicating that cases were less frequently exposed than controls. These included (1) drugs with prior evidence for a causal relationship (e.g., megestrol); (2) drugs without prior evidence for a causal relationship, but potentially worth further exploration (e.g., donepezil, epoetin alfa); (3) drugs with alternative biologic explanations for the association (e.g., sevelamer); and (4) drugs that may have resulted in statistical alerts due to their correlation with drugs that alerted for other reasons. CONCLUSIONS: This exploratory drug-screening study identified several potential targets for follow-up studies to further evaluate and determine if they may prevent or delay progression to advanced AMD.

14.
Am Heart J ; 228: 36-43, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32768690

RESUMO

BACKGROUND: Less than half of patients with cardiometabolic disease consistently take prescribed medications. While health insurers and some delivery organizations use claims to measure adherence, most clinicians do not have access during routine interactions. Self-reported scales exist, but their practical utility is often limited by length or cost. By contrast, the accuracy of a new 3-item self-reported measure has been demonstrated in individuals with HIV. We evaluated its concordance with claims-based adherence measures in cardiometabolic disease. METHODS: We used data from a recently-completed pragmatic trial of patients with cardiometabolic conditions. After 12 months of follow-up, intervention subjects were mailed a survey with the 3-item measure that queries about medication use in the prior 30 days. Responses were linearly transformed and averaged. Adherence was also measured in claims in month 12 and months 1-12 of the trial using proportion of days covered (PDC) metrics. We compared validation metrics for non-adherence for self-report (average <0.80) compared with claims (PDC <0.80). RESULTS: Of 459 patients returning the survey (response rate: 43.5%), 50.1% were non-adherent in claims in month 12 while 20.9% were non-adherent based on the survey. Specificity of the 3-item metric for non-adherence was high (month 12: 0.83). Sensitivity was relatively poor (month 12: 0.25). Month 12 positive and negative predictive values were 0.59 and 0.52, respectively. CONCLUSIONS: A 3-item self-reported measure has high specificity but poor sensitivity for non-adherence versus claims in cardiometabolic disease. Despite this, the tool could help target those needing adherence support, particularly in the absence of claims data.


Assuntos
Adesão à Medicação/estatística & dados numéricos , Síndrome Metabólica/tratamento farmacológico , Medidas de Resultados Relatados pelo Paciente , Inquéritos e Questionários/normas , Feminino , Humanos , Revisão da Utilização de Seguros/estatística & dados numéricos , Masculino , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/psicologia , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Disponibilidade de Medicamentos Via Internet , Consulta Remota/métodos , Consulta Remota/estatística & dados numéricos , Autorrelato/normas , Sensibilidade e Especificidade , Estados Unidos/epidemiologia
15.
Am J Manag Care ; 26(8): 340-347, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32835461

RESUMO

OBJECTIVES: To better understand patients' and pharmacists' preferences for and experiences with changes in pill appearance (size, shape, color, and markings). STUDY DESIGN: Cross-sectional. METHODS: We conducted independent national surveys of patients 50 years and older taking generic drugs for depression, diabetes, epilepsy, HIV, hyperlipidemia, or hypertension and of licensed pharmacists practicing in chain, franchise, or independent pharmacies. Responses were collected between January and April 2016. RESULTS: Of 1000 patient respondents (30% response rate), most reported experiencing changes in pill appearance (51%) and preferred to be notified about them (82%), but less than half recalled being notified (verbally: 36%; via sticker: 45%). Among patients who reported experiencing a change, 12% reported stopping their medication or using it less frequently. Of 710 pharmacist respondents (33% response rate), many reported changes in pill appearance occurring frequently in their pharmacies (47% reported that changes occurred 6 or more times per month) and more than three-fourths reported notifying patients about them often (verbally: 88%; via sticker: 77%). CONCLUSIONS: Our findings reveal opportunities to improve patients' experiences with pill appearance changes through better notification practices and patient education.

16.
Am J Epidemiol ; 189(12): 1467-1477, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32639512

RESUMO

Using nationwide Danish registries, we conducted a population-based case-crossover study evaluating the association between switching from a vitamin K antagonist (VKA) to a direct oral anticoagulant (DOAC), and vice versa, and 30-day risks of bleeding and arterial thromboembolism in patients with atrial fibrillation (AF). The case-crossover population was identified among oral anticoagulant users during 2011-2018 (n = 123,217) as patients with AF with 1) a case-defining outcome and 2) an anticoagulant switch during the 180 days preceding the outcome. Odds ratios were estimated using conditional logistic regression by comparing the occurrence of switching during the 30-day window immediately preceding the outcome to that in reference windows in the same individual 60-180 days before the outcome. The case-crossover populations for switching from VKA to DOAC and DOAC to VKA comprised 1,382 and 287 case patients, respectively. Switching from VKA to DOAC, but not from DOAC to VKA, was associated with an increased short-term risk of bleeding (odds ratio = 1.42; 95% confidence intervals: 1.13, 1.79, and 1.06; and 0.64, 1.75, respectively) and ischemic stroke (odds ratio = 1.74; 95% confidence intervals: 1.21, 2.51, and 0.92; and 0.46, 1.83, respectively). Our findings suggest that switching from VKA to DOAC is an intermittent risk factor of bleeding and ischemic stroke in patients with AF.

17.
Pharmacoepidemiol Drug Saf ; 29(8): 890-903, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32524701

RESUMO

PURPOSE: Upper gastrointestinal bleeding (UGIB) is a severe and frequent drug-related event. In order to enable efficient drug safety alert generation in the French National Healthcare System database (SNDS), we assessed and calibrated empirically case-based designs to identify drug associated with UGIB risk. METHODS: All cases of UGIB were extracted from SNDS (2009-2014) using two definitions. Positive and negative drug controls were used to compare 196 self-controlled case series (SCCS), case-control (CC) and case-population (CP) design variants. Each variant was evaluated in a 1/10th population sample using area under the receiver operating curve (AUC) and mean square error (MSE). Parameters that had major impacts on results were identified through logistic regression. Optimal designs were replicated in the unsampled population. RESULTS: Using a specific UGIB definition, AUCs ranged from 0.64 to 0.80, 0.44 to 0.61 and 0.50 to 0.67, for SCCS, CC and CP, respectively. MSE ranged from 0.07 to 0.39, 0.83 to 1.33 and 1.96 to 4.6, respectively. Univariate regressions showed that high AUCs were achieved with SCCS with multiple drug adjustment and a 30-day risk window starting at exposure. The top-performing SCCS variant in the unsampled population yielded an AUC = 0.84 and MSE = 0.14, with 10/36 negative controls presenting significant estimates. CONCLUSIONS: SCCS adjusting for multiple drugs and using a 30-day risk window has the potential to generate UGIB-related alerts in the SNDS and hypotheses on its potential population impact. Negative control implementation highlighted that low systematic error was generated but that protopathic bias and confounding by indication remained unaddressed issues.

18.
Pharmacoepidemiol Drug Saf ; 29(9): 1079-1085, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32548875

RESUMO

PURPOSE: The case-crossover design is increasingly used to evaluate the effects of chronic medications; however, as traditionally implemented in pharmacoepidemiology, with referent period preceding the outcome, it may lead to bias in the presence of persistent exposures. We aimed to evaluate the extent and magnitude of bias in case-crossover analyses of chronic and persistent exposures, using simulations. METHODS: We simulated cohorts with either 30-day, 180-day, or 2-year exposure duration; and with varying degrees of persistence (10%, 30%, 50%, 70%, or 90% of patients not stopping exposure). We evaluated all scenarios under the null and the scenario with 30% persistence under varying exposure effects (odds ratios of 0.25 to 4.0). Cohorts were analyzed using conditional logistic regression that compared the odds of exposure on the outcome day to the odds of exposure on a referent day 30 days prior to the outcome. We further implemented the case-time-control design to evaluate its ability to adjust for bias from persistence. RESULTS: Case-crossover analyses produced unbiased estimates across all scenarios without persistent users, regardless of exposure duration. In scenarios where some patients persisted on treatment, case-crossover analyses resulted in upward bias, which increased with increasing proportion of persistent users, but did not vary substantially in relation to the magnitude of the true effect. Case-time-control analyses removed bias in all scenarios. CONCLUSIONS: Investigators should be aware of bias due to treatment persistence in unidirectional case-crossover analyses of chronic medications, which can be remedied with a control group of similarly persistent noncases.

19.
Sci Rep ; 10(1): 10070, 2020 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-32572080

RESUMO

Sulfonylureas are commonly used to treat type 2 diabetes mellitus. Despite awareness of their effects on cardiac physiology, a knowledge gap exists regarding their effects on cardiovascular events in real-world populations. Prior studies reported sulfonylurea-associated cardiovascular death but not serious arrhythmogenic endpoints like sudden cardiac arrest (SCA) or ventricular arrhythmia (VA). We assessed the comparative real-world risk of SCA/VA among users of second-generation sulfonylureas: glimepiride, glyburide, and glipizide. We conducted two incident user cohort studies using five-state Medicaid claims (1999-2012) and Optum Clinformatics commercial claims (2000-2016). Outcomes were SCA/VA events precipitating hospital presentation. We used Cox proportional hazards models, adjusted for high-dimensional propensity scores, to generate adjusted hazard ratios (aHR). We identified 624,406 and 491,940 sulfonylurea users, and 714 and 385 SCA/VA events, in Medicaid and Optum, respectively. Dataset-specific associations with SCA/VA for both glimepiride and glyburide (vs. glipizide) were on opposite sides of and could not exclude the null (glimepiride: aHRMedicaid 1.17, 95% CI 0.96-1.42; aHROptum 0.84, 0.65-1.08; glyburide: aHRMedicaid 0.87, 0.74-1.03; aHROptum 1.11, 0.86-1.42). Database differences in data availability, populations, and documentation completeness may have contributed to the incongruous results. Emphasis should be placed on assessing potential causes of discrepancies between conflicting studies evaluating the same research question.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...