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2.
Am Heart J ; 226: 94-113, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32526534

RESUMO

Disparities in the control of hypertension and other cardiovascular disease risk factors are well-documented in the United States, even among patients seen regularly in the healthcare system. Few existing approaches explicitly address disparities in hypertension care and control. This paper describes the RICH LIFE Project (Reducing Inequities in Care of Hypertension: Lifestyle Improvement for Everyone) design. METHODS: RICH LIFE is a two-arm, cluster-randomized trial, comparing the effectiveness of enhanced standard of care, "Standard of Care Plus" (SCP), to a multi-level intervention, "Collaborative Care/Stepped Care" (CC/SC), for improving blood pressure (BP) control and patient activation and reducing disparities in BP control among 1890 adults with uncontrolled hypertension and at least one other cardiovascular disease risk factor treated at 30 primary care practices in Maryland and Pennsylvania. Fifteen practices randomized to the SCP arm receive standardized BP measurement training; race/ethnicity-specific audit and feedback of BP control rates; and quarterly webinars in management practices, quality improvement and disparities reduction. Fifteen practices in the CC/SC arm receive the SCP interventions plus implementation of the collaborative care model with stepped-care components (community health worker referrals and virtual specialist-panel consults). The primary clinical outcome is BP control (<140/90 mm Hg) at 12 months. The primary patient-reported outcome is change from baseline in self-reported patient activation at 12 months. DISCUSSION: This study will provide knowledge about the feasibility of leveraging existing resources in routine primary care and potential benefits of adding supportive community-facing roles to improve hypertension care and reduce disparities. TRIAL REGISTRATION: Clinicaltrials.govNCT02674464.


Assuntos
Pesquisa Comparativa da Efetividade/métodos , Assistência à Saúde/métodos , Disparidades em Assistência à Saúde , Hipertensão/prevenção & controle , Ensaios Clínicos Pragmáticos como Assunto/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Humanos , Resultado do Tratamento , Estados Unidos
3.
Value Health ; 23(6): 751-759, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32540233

RESUMO

OBJECTIVES: To assess the performance of unanchored matching-adjusted indirect comparison (MAIC) by matching on first moments or higher moments in a cross-study comparisons under a variety of conditions. A secondary objective was to gauge the performance of the method relative to propensity score weighting (PSW). METHODS: A simulation study was designed based on an oncology example, where MAIC was used to account for differences between a contemporary trial in which patients had more favorable characteristics and a historical control. A variety of scenarios were then tested varying the setup of the simulation study, including violating the implicit or explicit assumptions of MAIC. RESULTS: Under ideal conditions and under a variety of scenarios, MAIC performed well (shown by a low mean absolute error [MAE]) and was unbiased (shown by a mean error [ME] of about zero). The performance of the method deteriorated where the matched characteristics had low explanatory power or there was poor overlap between studies. Only when important characteristics are not included in the matching did the method become biased (nonzero ME). Where the method showed poor performance, this was exaggerated if matching was also performed on the variance (ie, higher moments). Relative to PSW, MAIC provided similar results in most circumstances, although it exhibited slightly higher MAE and a higher chance of exaggerating bias. CONCLUSIONS: MAIC appears well suited to adjust for cross-trial comparisons provided the assumptions underpinning the model are met, with relatively little efficiency loss compared with PSW.


Assuntos
Pesquisa Comparativa da Efetividade/métodos , Simulação por Computador , Modelos Teóricos , Neoplasias/terapia , Viés , Ensaios Clínicos como Assunto/métodos , Humanos , Pontuação de Propensão
4.
Ann Rheum Dis ; 79(7): 883-890, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32381560

RESUMO

OBJECTIVES: Target trial emulation is an intuitive design framework that encourages investigators to formulate their comparative effectiveness research (CER) question as a hypothetical randomised controlled trial (RCT). Our aim was to systematically review CER studies in rheumatoid arthritis (RA) to provide examples of design limitations that could be avoided using target trial emulation, and how these limitations might introduce bias. METHODS: We searched for head-to-head CER studies of biologic disease modifying anti-rheumatic drugs (DMARDs) in RA. Study designs were reviewed for seven components of the target trial emulation framework: eligibility criteria, treatment strategies, assignment procedures, follow-up period, outcome, causal contrasts of interest (ie, intention-to-treat (ITT) or per-protocol effect) and analysis plan. Hypothetical trials corresponding to the reported methods were assessed to identify design limitations that would have been avoided with an explicit target trial protocol. Analysis of the primary effectiveness outcome was chosen where multiple analyses were performed. RESULTS: We found 31 CER studies, of which 29 (94%) had at least one design limitation belonging to seven components. The most common limitations related to: (1) eligibility criteria: 19/31 (61%) studies used post-baseline information to define baseline eligibility; (2) causal contrasts: 25 (81%) did not define whether ITT or per-protocol effects were estimated and (3) assignment procedures: 13 (42%) studies did not account for confounding by indication or relied solely on statistical confounder selection. CONCLUSIONS: Design limitations were found in 94% of observational CER studies in RA. Target trial emulation is a structured approach for designing observational CER studies that helps to avoid potential sources of bias.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Pesquisa Comparativa da Efetividade/estatística & dados numéricos , Estudos Observacionais como Assunto/estatística & dados numéricos , Projetos de Pesquisa , Pesquisa Comparativa da Efetividade/métodos , Humanos , Estudos Observacionais como Assunto/métodos
6.
Trials ; 21(1): 83, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31937341

RESUMO

BACKGROUND: Bayesian adaptive designs can be more efficient than traditional methods for multi-arm randomised controlled trials. The aim of this work was to demonstrate how Bayesian adaptive designs can be constructed for multi-arm phase III clinical trials and assess potential benefits that these designs offer. METHODS: We constructed several alternative Bayesian adaptive designs for the Collaborative Ankle Support Trial (CAST), which was a randomised controlled trial that compared four treatments for severe ankle sprain. These designs incorporated response adaptive randomisation (RAR), arm dropping, and early stopping for efficacy or futility. We studied the operating characteristics of the Bayesian designs via simulation. We then virtually re-executed the trial by implementing the Bayesian adaptive designs using patient data sampled from the CAST study to demonstrate the practical applicability of the designs. RESULTS: We constructed five Bayesian adaptive designs, each of which had high power and recruited fewer patients on average than the original designs target sample size. The virtual executions showed that most of the Bayesian designs would have led to trials that declared superiority of one of the interventions over the control. Bayesian adaptive designs with RAR or arm dropping were more likely to allocate patients to better performing arms at each interim analysis. Similar estimates and conclusions were obtained from the Bayesian adaptive designs as from the original trial. CONCLUSIONS: Using CAST as an example, this case study shows how Bayesian adaptive designs can be constructed for phase III multi-arm trials using clinically relevant decision criteria. These designs demonstrated that they can potentially generate earlier results and allocate more patients to better performing arms. We recommend the wider use of Bayesian adaptive approaches in phase III clinical trials. TRIAL REGISTRATION: CAST study registration ISRCTN, ISRCTN37807450. Retrospectively registered on 25 April 2003.


Assuntos
Traumatismos do Tornozelo/terapia , Medicina de Emergência/organização & administração , Recuperação de Função Fisiológica/fisiologia , Traumatismos do Tornozelo/diagnóstico , Teorema de Bayes , Braquetes/efeitos adversos , Braquetes/estatística & dados numéricos , Ensaios Clínicos Fase III como Assunto , Pesquisa Comparativa da Efetividade/métodos , Pesquisa Comparativa da Efetividade/estatística & dados numéricos , Simulação por Computador , Tomada de Decisões/ética , Medicina de Emergência/estatística & dados numéricos , Inglaterra/epidemiologia , Humanos , Ortopedia , Projetos de Pesquisa , Índices de Gravidade do Trauma
7.
Clin Trials ; 17(1): 77-86, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31647326

RESUMO

BACKGROUND: Many studies, such as a study of comparative effectiveness, entail a comparison of the beneficial and adverse effects of multiple K> 2 competing therapies. Often, the analysis consists of a comparison of the K groups using an omnibus (T2-like) test for any difference among the groups followed by pairwise comparisons with adjustments for multiple tests. METHODS: We evaluate the properties of an analysis strategy in which each group is compared to the average of the others in hopes of establishing the overall superiority (or harm) of at least one of the therapies. Testing of one-versus-others can be accomplished for virtually any model using simple tests, and the type I error probability α can be controlled by conducting such tests under the closed testing principle. Testing using linear models, the family of generalized linear models, and Cox proportional hazards models is described with examples. RESULTS: Since each tested hypothesis compares one treatment to the average of the others, the K-level null hypothesis in the tree of closed testing is equivalent to any of the (K-1)-level tests, thus reducing the number of tests required. This applies to linear, generalized linear, and Cox proportional hazards models. While the Bonferroni, Holm, and Hommel procedures preserve the desired level α, all are conservative relative to closed one-versus-others testing and closed testing in general provides greater power. CONCLUSION: Testing each of the multiple treatments versus the average of the others is readily and efficiently conducted under the closed testing principle and may be especially useful in the assessment of studies of comparative effectiveness.


Assuntos
Pesquisa Comparativa da Efetividade/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Algoritmos , Pesquisa Comparativa da Efetividade/estatística & dados numéricos , Humanos , Modelos Lineares , Modelos de Riscos Proporcionais
8.
Nicotine Tob Res ; 22(3): 354-362, 2020 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-30590810

RESUMO

INTRODUCTION: Preliminary trial data suggest group-delivered acceptance and commitment therapy (ACT) might be effective for smoking cessation. If so, this could offer a viable alternative to mainstream behavioral therapies, such as those grounded in cognitive behavioral therapy (CBT). The goal of the current study was to compare the effectiveness of group-delivered ACT versus group-delivered CBT in a rigorous randomized trial design with long-term follow-up. METHODS: Participants (n = 450) were recruited from the Kaiser Permanente Washington health care system and randomized to either ACT-based group counseling or an attention-matched CBT-based group program. All were prescribed an 8-week course of nicotine patches. The primary outcome was self-reported 30-day point prevalence abstinence at 12 months post-randomization assessed with missing values imputed as smoking. Sensitivity analyses using multiple imputation and complete cases were examined, as were biochemically confirmed and 6-month outcomes. RESULTS: Thirty-day point prevalence abstinence rates at the 12-month follow-up did not differ between study arms in the primary analysis (13.8% ACT vs. 18.1% CBT, adjusted odds ratio = 0.68 [95% CI = 0.35 to 1.27], p = .23) or the sensitivity analyses. CONCLUSIONS: Group-based ACT and CBT had similar long-term quit rates in this methodologically rigorous randomized trial. Group-based ACT is a reasonable alternative to group-based CBT for smoking cessation. IMPLICATIONS: This study compared the effectiveness of group-based ACT with group-based CBT for smoking cessation using a rigorous, large-scale, attention-matched, randomized trial with 1-year follow-up. One-year cessation rates did not differ between group-based ACT and CBT, suggesting ACT-based intervention is a reasonable alternative to CBT-based counseling for smoking cessation. The results add to the nascent but growing literature assessing ACT and other mindfulness-based treatments for smoking cessation.


Assuntos
Terapia de Aceitação e Compromisso/métodos , Terapia Cognitivo-Comportamental/métodos , Pesquisa Comparativa da Efetividade/métodos , Aconselhamento , Abandono do Hábito de Fumar/métodos , Fumar Tabaco/terapia , Dispositivos para o Abandono do Uso de Tabaco , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Motivação , Fumar/terapia , Fumar Tabaco/psicologia
9.
Implement Sci ; 14(1): 100, 2019 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-31805968

RESUMO

BACKGROUND: Disseminating care guidelines into clinical practice remains challenging, partly due to inadequate evidence on how best to help clinics incorporate new guidelines into routine care. This is particularly true in safety net community health centers (CHCs). METHODS: This pragmatic comparative effectiveness trial used a parallel mixed methods design. Twenty-nine CHC clinics were randomized to receive increasingly intensive implementation support (implementation toolkit (arm 1); toolkit + in-person training + training webinars (arm 2); toolkit + training + webinars + offered practice facilitation (arm 3)) targeting uptake of electronic health record (EHR) tools focused on guideline-concordant cardioprotective prescribing for patients with diabetes. Outcomes were compared across study arms, to test whether increased support yielded additive improvements, and with 137 non-study CHCs that share the same EHR as the study clinics. Quantitative data from the CHCs' EHR were used to compare the magnitude of change in guideline-concordant ACE/ARB and statin prescribing, using adjusted Poisson regressions. Qualitative data collected using diverse methods (e.g., interviews, observations) identified factors influencing the quantitative outcomes. RESULTS: Outcomes at CHCs receiving higher-intensity support did not improve in an additive pattern. ACE/ARB prescribing did not improve in any CHC group. Statin prescribing improved overall and was significantly greater only in the arm 1 and arm 2 CHCs compared with the non-study CHCs. Factors influencing the finding of no additive impact included: aspects of the EHR tools that reduced their utility, barriers to providing the intended implementation support, and study design elements, e.g., inability to adapt the provided support. Factors influencing overall improvements in statin outcomes likely included a secular trend in awareness of statin prescribing guidelines, selection bias where motivated clinics volunteered for the study, and study participation focusing clinic staff on the targeted outcomes. CONCLUSIONS: Efforts to implement care guidelines should: ensure adaptability when providing implementation support and conduct formative evaluations to determine the optimal form of such support for a given clinic; consider how study data collection influences adoption; and consider barriers to clinics' ability to use/accept implementation support as planned. More research is needed on supporting change implementation in under-resourced settings like CHCs. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02325531. Registered 15 December 2014.


Assuntos
Centros Comunitários de Saúde/normas , Pesquisa Comparativa da Efetividade/métodos , Fidelidade a Diretrizes/estatística & dados numéricos , Implementação de Plano de Saúde/métodos , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos de Pesquisa , Adulto Jovem
10.
Lancet ; 394(10211): 1816-1826, 2019 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-31668726

RESUMO

BACKGROUND: Uncertainty remains about the optimal monotherapy for hypertension, with current guidelines recommending any primary agent among the first-line drug classes thiazide or thiazide-like diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, dihydropyridine calcium channel blockers, and non-dihydropyridine calcium channel blockers, in the absence of comorbid indications. Randomised trials have not further refined this choice. METHODS: We developed a comprehensive framework for real-world evidence that enables comparative effectiveness and safety evaluation across many drugs and outcomes from observational data encompassing millions of patients, while minimising inherent bias. Using this framework, we did a systematic, large-scale study under a new-user cohort design to estimate the relative risks of three primary (acute myocardial infarction, hospitalisation for heart failure, and stroke) and six secondary effectiveness and 46 safety outcomes comparing all first-line classes across a global network of six administrative claims and three electronic health record databases. The framework addressed residual confounding, publication bias, and p-hacking using large-scale propensity adjustment, a large set of control outcomes, and full disclosure of hypotheses tested. FINDINGS: Using 4·9 million patients, we generated 22 000 calibrated, propensity-score-adjusted hazard ratios (HRs) comparing all classes and outcomes across databases. Most estimates revealed no effectiveness differences between classes; however, thiazide or thiazide-like diuretics showed better primary effectiveness than angiotensin-converting enzyme inhibitors: acute myocardial infarction (HR 0·84, 95% CI 0·75-0·95), hospitalisation for heart failure (0·83, 0·74-0·95), and stroke (0·83, 0·74-0·95) risk while on initial treatment. Safety profiles also favoured thiazide or thiazide-like diuretics over angiotensin-converting enzyme inhibitors. The non-dihydropyridine calcium channel blockers were significantly inferior to the other four classes. INTERPRETATION: This comprehensive framework introduces a new way of doing observational health-care science at scale. The approach supports equivalence between drug classes for initiating monotherapy for hypertension-in keeping with current guidelines, with the exception of thiazide or thiazide-like diuretics superiority to angiotensin-converting enzyme inhibitors and the inferiority of non-dihydropyridine calcium channel blockers. FUNDING: US National Science Foundation, US National Institutes of Health, Janssen Research & Development, IQVIA, South Korean Ministry of Health & Welfare, Australian National Health and Medical Research Council.


Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Adolescente , Adulto , Idoso , Antagonistas de Receptores de Angiotensina/efeitos adversos , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/efeitos adversos , Bloqueadores dos Canais de Cálcio/efeitos adversos , Bloqueadores dos Canais de Cálcio/uso terapêutico , Criança , Estudos de Coortes , Pesquisa Comparativa da Efetividade/métodos , Bases de Dados Factuais , Diuréticos/efeitos adversos , Diuréticos/uso terapêutico , Medicina Baseada em Evidências/métodos , Feminino , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/prevenção & controle , Humanos , Hipertensão/complicações , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/prevenção & controle , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Adulto Jovem
11.
J Manag Care Spec Pharm ; 25(10): 1125-1132, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31556821

RESUMO

BACKGROUND: Understanding the real-world use of oral oncolytics is essential to assess drug effectiveness. Retrospective analyses using medical and pharmacy claims data allow observation of drug use patterns and health outcomes. However, studies of medication adherence to oral oncolytics may not be sufficient in characterizing exposure because they typically measure refill frequency, not the administered dose or dose changes. Patients who appear fully adherent by traditional measures may be receiving different doses and experiencing differing effectiveness. Relative dose intensity (RDI) is a measure that has been used for intravenous drugs to capture the amount of a particular chemotherapeutic agent administered per unit of time (dose intensity), expressed as the fraction of the amount recommended in evidence-based guidelines. Such a measure would be useful for real-world studies of comparative effectiveness to characterize patient exposure to oral oncolytics. OBJECTIVE: To identify studies that used administrative claims data to measure real-world oral oncolytic dose intensity, RDI, or similar constructs. METHODS: Two health sciences librarians conducted a literature search (PubMed, January 1, 1809-February 6, 2018) including terms in each of the following concept areas: oncology drugs, dosage, and retrospective data sources. At least 2 reviewers scanned each title and abstract of publications retrieved from PubMed. Abstracts that indicated the study reported dose or related concepts and oral oncolytics using retrospective data sources were marked for full-text review. During full-text review, papers were excluded if they did not study oral oncolytics (i.e., only described intravenous chemotherapy); if they did not report drug dosage; or if the study was not retrospective. Resulting studies were included for full-text data extraction. RESULTS: Of the 1,640 publications returned from the search, 41 were marked for full-text review. Full-text review established that 17 studies addressed a concept related to dose of oral oncolytics using retrospective data. Twenty-four studies were excluded: 11 did not measure dose; 9 did not study oral oncolytics; and 4 were not retrospective studies. Among the 17 articles marked for extraction, 5 articles reported dose intensity or RDI using medical records or electronic health record (EHR) data. CONCLUSIONS: This study reveals not only the need for a claims-based measure of dose intensity for oral oncolytics, but also provides a basis for the development of such a measure based on previous EHR-based studies. While several claims data studies have characterized oral oncolytic dosing and duration, we found that no studies combined these dimensions into a single measure such as dose intensity. Methods using EHR data may be translatable to a claims data study. Future research is needed to develop and validate such measures. DISCLOSURES: Novartis Pharmaceuticals provided funding for this study and is a manufacturer of oral onalytics, which is under study in this article. Arcona and Zacker are employees of Novartis. Slejko reports grants from PhRMA, PhRMA Foundation, and Takeda Pharmaceuticals and consulting fees from Pfizer, outside the submitted work. Stuart reports consulting fees from the University of Maryland during the study. The other authors have nothing to disclose. The preliminary findings of this study were presented in a poster at AMCP Nexus 2018, October 22-25, 2018, in Orlando, FL.


Assuntos
Antineoplásicos Imunológicos/administração & dosagem , Pesquisa Comparativa da Efetividade/métodos , Neoplasias/tratamento farmacológico , Administração Oral , Pesquisa Comparativa da Efetividade/estatística & dados numéricos , Relação Dose-Resposta a Droga , Esquema de Medicação , Humanos , Adesão à Medicação/estatística & dados numéricos , Resultado do Tratamento
12.
J Manag Care Spec Pharm ; 25(10): 1096-1101, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31556822

RESUMO

Genetic testing technology is rapidly evolving with the growth of personalized medicine. While test evaluation typically relies on laboratory measures of performance, tests can be costly and analytically and ethically complex. A more fulsome consideration of value is warranted to inform adoption and appropriate use. Herein we describe a methodology for developing novel clinician- and patient-reported measures of clinical and personal utility, aiming to capture the informational value of genome diagnostic tests. Adhering to core measurement science principles and standards, our 4-step process includes (1) tool development through scoping reviews and stakeholder interviews and surveys; (2) tool validation through prospective cohort studies to establish construct validity, inter- and intra-rater reliability; (3) tool application using comparative effectiveness assessment to gauge the comparative value of different types of genetic tests; and (4) tool dissemination, leveraging existing partnerships with international stakeholders to spur additional validation studies, comparative effectiveness research, cost-effectiveness analysis, and evidence-informed policy. A scoping review of the clinical utility literature informed the development of a preliminary 25-item index. Qualitative interviews with 35 clinicians further informed the definition of our utility construct, item content, and item importance. Stakeholder surveys with 113 clinicians enabled further feedback on item content, importance, sensibility, response, and scoring options. An 18-item tool, the "Clinician-reported Genetic testing Utility InDEx" (C-GUIDE), is now undergoing validation, while development work on the patient-reported measure of utility is underway. A methodologically innovative approach to the development of stakeholder-informed and clinimetrically sound measures of value for personalized medicine tests will assist technology users and decision makers globally. DISCLOSURES: This work was supported by the Canadian Institutes of Health Research Operating Grant (#PJT-152880) and the PhRMA Foundation Challenge Award. Publication of the study methodology or findings generated therein was not contingent on the sponsor's approval or censorship of the manuscript. The authors have nothing to disclose. Results from this study were presented as a poster at the 40th Annual North American Meeting of the Society for Medical Decision Making; October 14, 2018; Montreal, QC; the Annual Meeting of the American Society of Human Genetics; October 18, 2018; San Diego, CA; and as an oral presentation at the Annual Meeting of the Canadian Association for Health Services and Policy Research; May 31, 2018; Montreal, QC.


Assuntos
Tomada de Decisão Clínica/métodos , Pesquisa Comparativa da Efetividade/métodos , Testes Genéticos/normas , Genoma Humano/genética , Medicina de Precisão/normas , Análise Custo-Benefício/métodos , Prática Clínica Baseada em Evidências/economia , Prática Clínica Baseada em Evidências/normas , Testes Genéticos/economia , Humanos , Medidas de Resultados Relatados pelo Paciente , Reprodutibilidade dos Testes , Participação dos Interessados , Seguro de Saúde Baseado em Valor/economia
13.
Semin Radiat Oncol ; 29(4): 302-305, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31472729

RESUMO

A principle goal of research in Oncology is to determine the optimal treatment for our patients. This often takes the form of comparing 2 existing therapies to one another to determine which is superior, or to introduce a new therapy and determine if it is superior or noninferior to the existing standard of care. This type of research is termed comparative effectiveness research (CER), and the gold-standard is through the conduct of randomized trials. This is the preferred approach, and the only true methodologic approach that can assign a cause-and-effect relationship between a treatment effect and the observed outcome. An alternative approach that is gaining popularity is the use of population-based registry analysis given that it is quicker, cheaper, and easier to perform. However, there are unavoidable forms of bias and confounding that exist when using observational research to perform CER, and recent evidence suggests that population-based CER often results in erroneous results, and that statistical methods to minimize bias are ineffective to overcome the numerous limitations of these databases. In this article, the strengths and weaknesses of both randomized and observational research will be discussed.


Assuntos
Pesquisa Comparativa da Efetividade/métodos , Gerenciamento de Dados/métodos , Oncologia/métodos , Estudos Observacionais como Assunto/métodos , Projetos de Pesquisa , Humanos
14.
J Comp Eff Res ; 8(10): 815-826, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31368793

RESUMO

Background: Recruitment of participants into research studies, especially individuals from minority groups, is challenging; lack of diversity may lead to biased findings. Aim: To explore beliefs about research participation among individuals who were approached and eligible for the GRADE study. Methods: In-depth qualitative telephone interviews with randomized participants (n = 25) and eligible individuals who declined to enroll (n = 26). Results: Refusers and consenters differed in trust and perceptions of risk, benefits and burden of participation. Few participants understood how comparative effectiveness research differed from other types of trials; however, some features of comparative effectiveness research were perceived as lower risk. Conclusion: We identified facilitators and addressable barriers to participation in research studies.


Assuntos
Pesquisa Comparativa da Efetividade/métodos , Pesquisa Comparativa da Efetividade/estatística & dados numéricos , Seleção de Pacientes , Adulto , Idoso , Feminino , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Pesquisa Qualitativa , Confiança/psicologia
15.
Pharmacoepidemiol Drug Saf ; 28(10): 1290-1298, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31385394

RESUMO

PURPOSE: In nonexperimental comparative effectiveness research, restricting analysis to subjects with better overlap of covariate distributions, hence greater treatment equipoise, helps balance the groups compared and can improve validity. Three alternative approaches, derived from different perspectives, implement restriction by trimming observations in the tails of the propensity score (PS). Across approaches, we compared the relationships between the overlap in treatment-specific PS distributions and the size of the balanced study population after trimming. METHODS: The three trimming approaches considered were absolute trimming to the range 0.1

Assuntos
Pesquisa Comparativa da Efetividade/métodos , Modelos Estatísticos , Viés , Simulação por Computador , Interpretação Estatística de Dados , Pontuação de Propensão , Tamanho da Amostra
16.
Pediatr Rheumatol Online J ; 17(1): 43, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31307476

RESUMO

BACKGROUND: We designed and initiated a pilot comparative effectiveness study for juvenile localized scleroderma (jLS), for which there is limited evidence on best therapy. We evaluated the process we used, in relation to the specific protocol and to the general task of identifying strategies for implementing studies in rare pediatric diseases. METHODS: This was a prospective, multi-center, observational cohort study of 50 jLS patients initiating treatment, designed and conducted by the jLS group of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) from 2012 to 2015. A series of virtual and physical meetings were held to design the study, standardize clinical assessments, generate and refine disease activity and damage measures, and monitor the study. Patients were initiated on one of three standardized methotrexate-based treatment regimens (consensus treatment plans, CTPs) and monitored for 1 year. An optional bio-banking sub-study was included. RESULTS: The target enrollment of 50 patients was achieved over 26 months at 10 sites, with patients enrolled into all CTPs. Enrolled patients were typical for jLS. Study eligibility criteria were found to perform well, capturing patients thought appropriate for treatment studies. Minor modifications to the eligibility criteria, primarily to facilitate recruitment for future studies, were discussed with consensus agreement reached on them by the jLS group. There were marked differences in site preferences for specific CTPs, with half the sites treating all their patients with the same CTP. Most patients (88%) completed the study, and 68% participated in the bio-banking substudy. CONCLUSIONS: We demonstrate the feasibility of our approach for conducting comparative effectiveness research in a rare pediatric disease. Multi-center collaboration by dedicated investigators who met regularly was a key factor in the success of this project. Other factors that facilitate these studies include having a sufficient number of investigators to enroll in each regimen, and streamlining study approval and management.


Assuntos
Antirreumáticos/uso terapêutico , Pesquisa Comparativa da Efetividade/métodos , Glucocorticoides/uso terapêutico , Metotrexato/uso terapêutico , Esclerodermia Localizada/tratamento farmacológico , Escleroderma Sistêmico/tratamento farmacológico , Administração Intravenosa , Administração Oral , Adolescente , Criança , Quimioterapia Combinada , Estudos de Viabilidade , Feminino , Humanos , Masculino , Metilprednisolona/uso terapêutico , Projetos Piloto , Prednisona/uso terapêutico , Estudos Prospectivos , Doenças Raras , Adulto Jovem
17.
Lancet ; 394(10202): 939-951, 2019 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-31303314

RESUMO

BACKGROUND: Schizophrenia is one of the most common, burdensome, and costly psychiatric disorders in adults worldwide. Antipsychotic drugs are its treatment of choice, but there is controversy about which agent should be used. We aimed to compare and rank antipsychotics by quantifying information from randomised controlled trials. METHODS: We did a network meta-analysis of placebo-controlled and head-to-head randomised controlled trials and compared 32 antipsychotics. We searched Embase, MEDLINE, PsycINFO, PubMed, BIOSIS, Cochrane Central Register of Controlled Trials (CENTRAL), WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov from database inception to Jan 8, 2019. Two authors independently selected studies and extracted data. We included randomised controlled trials in adults with acute symptoms of schizophrenia or related disorders. We excluded studies in patients with treatment resistance, first episode, predominant negative or depressive symptoms, concomitant medical illnesses, and relapse-prevention studies. Our primary outcome was change in overall symptoms measured with standardised rating scales. We also extracted data for eight efficacy and eight safety outcomes. Differences in the findings of the studies were explored in metaregressions and sensitivity analyses. Effect size measures were standardised mean differences, mean differences, or risk ratios with 95% credible intervals (CrIs). Confidence in the evidence was assessed using CINeMA (Confidence in Network Meta-Analysis). The study protocol is registered with PROSPERO, number CRD42014014919. FINDINGS: We identified 54 417 citations and included 402 studies with data for 53 463 participants. Effect size estimates suggested all antipsychotics reduced overall symptoms more than placebo (although not statistically significant for six drugs), with standardised mean differences ranging from -0·89 (95% CrI -1·08 to -0·71) for clozapine to -0·03 (-0·59 to 0·52) for levomepromazine (40 815 participants). Standardised mean differences compared with placebo for reduction of positive symptoms (31 179 participants) varied from -0·69 (95% CrI -0·86 to -0·52) for amisulpride to -0·17 (-0·31 to -0·04) for brexpiprazole, for negative symptoms (32 015 participants) from -0·62 (-0·84 to -0·39; clozapine) to -0·10 (-0·45 to 0·25; flupentixol), for depressive symptoms (19 683 participants) from -0·90 (-1·36 to -0·44; sulpiride) to 0·04 (-0·39 to 0·47; flupentixol). Risk ratios compared with placebo for all-cause discontinuation (42 672 participants) ranged from 0·52 (0·12 to 0·95; clopenthixol) to 1·15 (0·36 to 1·47; pimozide), for sedation (30 770 participants) from 0·92 (0·17 to 2·03; pimozide) to 10·20 (4·72 to 29·41; zuclopenthixol), for use of antiparkinson medication (24 911 participants) from 0·46 (0·19 to 0·88; clozapine) to 6·14 (4·81 to 6·55; pimozide). Mean differences compared to placebo for weight gain (28 317 participants) ranged from -0·16 kg (-0·73 to 0·40; ziprasidone) to 3·21 kg (2·10 to 4·31; zotepine), for prolactin elevation (21 569 participants) from -77·05 ng/mL (-120·23 to -33·54; clozapine) to 48·51 ng/mL (43·52 to 53·51; paliperidone) and for QTc prolongation (15 467 participants) from -2·21 ms (-4·54 to 0·15; lurasidone) to 23·90 ms (20·56 to 27·33; sertindole). Conclusions for the primary outcome did not substantially change after adjusting for possible effect moderators or in sensitivity analyses (eg, when excluding placebo-controlled studies). The confidence in evidence was often low or very low. INTERPRETATION: There are some efficacy differences between antipsychotics, but most of them are gradual rather than discrete. Differences in side-effects are more marked. These findings will aid clinicians in balancing risks versus benefits of those drugs available in their countries. They should consider the importance of each outcome, the patients' medical problems, and preferences. FUNDING: German Ministry of Education and Research and National Institute for Health Research.


Assuntos
Antipsicóticos/uso terapêutico , Esquizofrenia/tratamento farmacológico , Administração Oral , Antipsicóticos/administração & dosagem , Antipsicóticos/efeitos adversos , Pesquisa Comparativa da Efetividade/métodos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
18.
BMC Health Serv Res ; 19(1): 416, 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31234857

RESUMO

BACKGROUND: Optimizing the organization of care for community-dwelling frail older people is an important issue in many Western countries. In Belgium, a series of complex, innovative, bottom-up interventions was recently designed and implemented to help frail older people live at home longer. As the effectiveness of these interventions may vary between different population groups according to their long-term care needs, they must be evaluated by comparison with a control group that has similar needs. METHODS: The goal was to identify target groups for these interventions and to establish control groups with similar needs and to explore, per group, the extent to which the utilization of long-term care is matched to needs. We merged two databases: a clinical prospective database and the routine administrative database for healthcare reimbursements. Through Principal Component Analysis followed by Clustering, the intervention group was first stratified into disability profiles. Per profile, comparable control groups for clinical variables were established, based on propensity scores. Using chi-squared tests and logistic regression analysis, long-term care utilization at baseline was then compared per profile and group studied. RESULTS: Stratification highlighted five disability profiles: people with low-level limitations; people with limitations in instrumental activities of daily life and low-level of cognitive impairment; people with functional limitations; people with functional and cognitive impairments; and people with functional, cognitive, and behavioral problems. These profiles made it possible to identify long-term care needs. For instance, at baseline, those who needed more assistance with hygiene tasks also received more personal nursing care (P < 0.05). However, there were some important discrepancies between the need for long-term care and its utilization: while 21% of patients who were totally dependent for hygiene tasks received no personal nursing care, personal nursing care was received by 33% of patients who could perform hygiene tasks. CONCLUSIONS: The disability profiles provide information on long-term care needs but not on the extent to which those needs are met. To assess the effectiveness of interventions, controls at baseline should have similar disability profiles and comparable long-term care utilization. To allow for large comparative effectiveness studies, these dimensions should ideally be available in routine databases.


Assuntos
Idoso Fragilizado , Serviços de Assistência Domiciliar/organização & administração , Vida Independente , Idoso , Idoso de 80 Anos ou mais , Bélgica , Pesquisa Comparativa da Efetividade/métodos , Pesquisa Comparativa da Efetividade/tendências , Bases de Dados Factuais , Pessoas com Deficiência/estatística & dados numéricos , Feminino , Previsões , Idoso Fragilizado/estatística & dados numéricos , Necessidades e Demandas de Serviços de Saúde , Humanos , Assistência de Longa Duração , Masculino , Estudos Prospectivos
19.
J Clin Epidemiol ; 114: 84-94, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31226413

RESUMO

OBJECTIVE: To test rapid approaches that use Drugs@FDA (a public database of approved drugs) and ClinicalTrials.gov to identify trials and to compare these two sources with bibliographic databases as an evidence base for a systematic review and network meta-analysis (NMA). STUDY DESIGN AND SETTING: We searched bibliographic databases, Drugs@FDA, and ClinicalTrials.gov for eligible trials on first-line glaucoma medications. We extracted data, assessed risk of bias, and examined the completeness and consistency of information provided by different sources. We fitted random-effects NMA models separately for trials identified from each source and for all unique trials from three sources. RESULTS: We identified 138 unique trials including 29,394 participants on 15 first-line glaucoma medications. For a given trial, information reported was sometimes inconsistent across data sources. Journal articles provided the most information needed for a systematic review; trial registrations provided the least. Compared to an NMA including all unique trials, we were able to generate reasonably precise effect estimates and similar relative rankings for available interventions using trials from Drugs@FDA alone (but not ClinicalTrials.gov). CONCLUSIONS: A rapid NMA approach using data from Drugs@FDA is feasible but has its own limitations. Reporting of trial design and results can be improved in both the drug approval packages and on ClinicalTrials.gov.


Assuntos
Ensaios Clínicos como Assunto , Pesquisa Comparativa da Efetividade/métodos , Aprovação de Drogas , Glaucoma/tratamento farmacológico , Metanálise em Rede , United States Food and Drug Administration , Bases de Dados Factuais , Estudos de Viabilidade , Humanos , Viés de Publicação , Sistema de Registros/estatística & dados numéricos , Revisões Sistemáticas como Assunto , Estados Unidos
20.
Complement Ther Med ; 44: 51-55, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31126575

RESUMO

INTRODUCTION: Perioperative symptoms such as pain, nausea and anxiety are often inadequately treated. We conducted a pragmatic trial to evaluate the impact of Complementary and Alternative Medicine (CAM) treatments on these symptoms, within the framework of a general surgery department that integrates CAM. METHODS: Patients ≥ 18 years referred to CAM treatments by surgical medical staff were allocated to standard of care with CAM treatment (CAM group) or without, according to patient preference and practitioner availability. CAM treatments included Acupuncture, Reflexology, or Guided Imagery. The primary outcome variable was the change from baseline in symptom severity, measured by Visual Analogue Scale (VAS). Patients and practitioners were asked to report any adverse effects associated with CAM treatments. RESULTS: A total of 1127 patients were enrolled, 916 undergoing 1214 CAM treatments and 211 controls. Socio-demographic characteristics were similar in both groups. Patients in the CAM group had more severe baseline symptoms. Symptom reduction was greater in the CAM group compared with controls, with a mean reduction in pain of -2.17 ±â€¯2.4 vs -0.29 ±â€¯2 (P < 0.0001); nausea -1.2 ±â€¯2.42 vs -0.3 ±â€¯1.94 (P < 0.0001); and anxiety -2.23 ±â€¯2.76 vs -0.03 ±â€¯2.54 (P < 0.0001). Acupuncture was more effective for nausea control. No significant adverse events were reported with any of the CAM therapies. CONCLUSION: CAM treatments provide additional relief to Standard Of Care (SOC) for perioperative symptoms. Larger randomized control trial studies with longer follow-ups are needed to confirm these benefits. The study is registered with clinical trials.gov at (NCT01733771).


Assuntos
Assistência Perioperatória/métodos , Período Perioperatório/métodos , Terapia por Acupuntura/métodos , Pesquisa Comparativa da Efetividade/métodos , Terapias Complementares/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Manipulações Musculoesqueléticas/métodos
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