Derivation and preliminary validation of an administrative claims-based algorithm for the effectiveness of medications for rheumatoid arthritis

Introduction

Administrative claims data have not commonly been used to study the clinical effectiveness of medications for rheumatoid arthritis (RA) because of the lack of a validated algorithm for this outcome. We created and tested a claims-based algorithm to serve as a proxy for the clinical effectiveness of RA medications.

Methods

We linked Veterans Health Administration (VHA) medical and pharmacy claims for RA patients participating in the longitudinal Department of Veterans Affairs (VA) RA registry (VARA). Among individuals for whom treatment with a new biologic agent or nonbiologic disease-modifying agent in rheumatic disease (DMARD) was being initiated and with registry follow-up at 1 year, VARA and administrative data were used to create a gold standard for the claims-based effectiveness algorithm. The gold standard outcome was low disease activity (LDA) (Disease Activity Score using 28 joint counts (DAS28) ≤ 3.2) or improvement in DAS28 by > 1.2 units at 12 ± 2 months, with high adherence to therapy. The claims-based effectiveness algorithm incorporated biologic dose escalation or switching, addition of new disease-modifying agents, increase in oral glucocorticoid use and dose as well as parenteral glucocorticoid injections.

Results

Among 1,397 patients, we identified 305 eligible biologic or DMARD treatment episodes in 269 unique individuals. The patients were primarily men (94%) with a mean (± SD) age of 62 ± 10 years. At 1 year, 27% of treatment episodes achieved the effectiveness gold standard. The performance characteristics of the effectiveness algorithm were as follows: positive predictive value, 76% (95% confidence interval (95% CI) = 71% to 81%); negative predictive value, 90% (95% CI = 88% to 92%); sensitivity, 72% (95% CI = 67% to 77%); and specificity, 91% (95% CI = 89% to 93%).

Conclusions

Administrative claims data may be useful in evaluating the effectiveness of medications for RA. Further validation of this effectiveness algorithm will be useful in assessing its generalizability and performance in other populations.     

Transforming scientific evidence into better consumer choices

Translational research using evidence-based and comparative effectiveness research continues to evolve, becoming a useful tool in improving informed consent and decision-making in the clinical setting. While in development, emerging technologies, including cellular and molecular biology, are leading to establishing evidence-based dental practices. One emerging technology, which conjoins bench proteomic findings to clinical decision-making for treatment intervention, is the Translational Evidence Mechanism. This mechanism was developed to be a foundation for a compact between researcher, translational researcher, clinician, and patient. The output of such a mechanism is the clinical practice guideline (CPG), an interactive tool for dentists and patients to game evidence in reaching optimum clinical decisions that correspond to individual patient preferences and values. As such, the clinical practice guideline requires the vesting of decision, utility, and cost best evidence. Evidence-based research provides decision data, a first attempt at supporting decision-making by providing best outcome data. Since then comparative effectiveness research has emerged, using systematic review analysis to compare similar treatments or procedures in maximizing the choice of the most effective cost/benefit option within the context of best evidence. With innovation in the clinical practice guideline for optimizing efficacy and comparative effectiveness research, evidence-based practices will shape a new approach to health-based systems that adhere to shared decision-making between bench scientists, healthcare providers and patients.     

Transforming scientific evidence into better consumer choices

Translational research using evidence-based and comparative effectiveness research continues to evolve, becoming a useful tool in improving informed consent and decision-making in the clinical setting. While in development, emerging technologies, including cellular and molecular biology, are leading to establishing evidence-based dental practices. One emerging technology, which conjoins bench proteomic findings to clinical decision-making for treatment intervention, is the Translational Evidence Mechanism. This mechanism was developed to be a foundation for a compact between researcher, translational researcher, clinician, and patient. The output of such a mechanism is the clinical practice guideline (CPG), an interactive tool for dentists and patients to game evidence in reaching optimum clinical decisions that correspond to individual patient preferences and values. As such, the clinical practice guideline requires the vesting of decision, utility, and cost best evidence. Evidence-based research provides decision data, a first attempt at supporting decision-making by providing best outcome data. Since then comparative effectiveness research has emerged, using systematic review analysis to compare similar treatments or procedures in maximizing the choice of the most effective cost/benefit option within the context of best evidence. With innovation in the clinical practice guideline for optimizing efficacy and comparative effectiveness research, evidence-based practices will shape a new approach to health-based systems that adhere to shared decision-making between bench scientists, healthcare providers and patients.     

Clinical analysis of 100 medicolegal cases.

OBJECTIVE--To find the reasons for legal claims against hospital doctors. DESIGN--Prospective analysis of requests for medical opinion submitted by solicitors during 1984-93 on legal claims against hospital doctors. SUBJECTS--100 successive cases: 98 from the United Kingdom and two from the Republic of Ireland. MAIN OUTCOME MEASURES--Principal underlying causes of claims. RESULTS--In 44 cases there was no serious clinical error. Of the 56 cases of clinical fault, seven were a failure of communication by doctors, 15 were an isolated error in otherwise good clinical management, 21 were errors that might not have occurred with better control of clinical practice (doctors exceeding their competence, poor clinical judgment, and poor teamwork), and 13 were major errors due to carelessness or incompetence. In 34 cases there was evidence of clinical fault that might escape clinical audit and medicolegal processes. Most of these legal claims have been or are likely to be withdrawn: only five plaintiffs have settled out of court, and 11 are pursuing their actions. CONCLUSIONS--To reduce the incidence of errors, hospital doctors should consult colleagues about difficult cases and specialists should maintain a broad interest in disease. The NHS clinical complaints procedure should be extended to cover potential claims, and serious cases should be subject to independent external assessment by experienced consultants.     

Bayesian Hierarchical Pattern Mixture Models for Comparative Effectiveness of Drugs and Drug Classes Using Healthcare Data: A Case Study Involving Antihypertensive Medications

Comparative effectiveness research aims, in part, to provide evidence most relevant to clinical decision making. One decision relevant to hypertensive patients is which therapeutic drug class is the most safe and effective. In addition, once a drug class has been chosen it would be useful to know whether there are differences in effectiveness between drugs within class. Randomized trials are unlikely to provide sufficient evidence for answering these questions. We therefore propose a modeling approach that can be used to address the questions using administrative databases. We propose a Bayesian hierarchical model, where drugs are nested within their corresponding class. We account for the type of missing data that are common in these databases using a pattern mixture model. The methodology is illustrated using data from a comparative effectiveness study of antihypertensive medications.     

冠状动脉CT造影对冠心病的临床诊断价值研究

目的:探讨研究冠状动脉CT造影检查对冠心病的临床诊断价值。方法:收集我院2012年1月至2013年10月共计70例临床怀疑为冠心病的患者,对这些患者分别进行冠状动脉CT造影检查和数字减影冠状动脉造影(DSA)检查,记录这两项检查所得结果及数据,以检查数据为基础对冠状动脉CT造影和数字减影冠状动脉造影检查的临床实验效果进行对比研究。结果:70例病人均可顺利完成以上两种检查,按照数字减影冠状动脉造影检查的标准,冠状动脉CT造影的敏感度为92.2%,特异度为97.4%、阳性预测率为90.5%、阴性预测率98%。结论:相对于数字减影冠状动脉造影检查,冠状动脉CT造影检查是一种更加安全、可靠、无创且更具临床指导意义的检测技术,因此可以推荐作为冠心病诊断的首选方法。     

冠状动脉CT造影对冠心病的临床诊断价值研究

目的：探讨研究冠状动脉CT造影检查对冠心病的临床诊断价值。方法：收集我院2012年1月至2013年10月共计70例临床怀疑为冠心病的患者,对这些患者分别进行冠状动脉CT造影检查和数字减影冠状动脉造影（DSA）检查,记录这两项检查所得结果及数据,以检查数据为基础对冠状动脉CT造影和数字减影冠状动脉造影检查的临床实验效果进行对比研究。结果：70例病人均可顺利完成以上两种检查,按照数字减影冠状动脉造影检查的标准,冠状动脉CT造影的敏感度为92.2%,特异度为97.4%、阳性预测率为90.5%、阴性预测率98%。结论：相对于数字减影冠状动脉造影检查,冠状动脉CT造影检查是一种更加安全、可靠、无创且更具临床指导意义的检测技术,因此可以推荐作为冠心病诊断的首选方法。     

Differential Cardiovascular Outcomes after Dipeptidyl Peptidase-4 Inhibitor,Sulfonylurea, and Pioglitazone Therapy,All in Combination with Metformin,for Type 2 Diabetes: A Population-Based Cohort Study

Background/ObjectivesData on the comparative effectiveness of oral antidiabetics on cardiovascular outcomes in a clinical practice setting are limited. This study sought to determine whether a differential risk of cardiovascular disease (CVD) exists for the combination of a dipeptidyl peptidase-4 (DPP-4) inhibitor plus metformin versus a sulfonylurea derivative plus metformin or pioglitazone plus metformin.MethodsWe conducted a cohort study of 349,476 patients who received treatment with a DPP-4 inhibitor, sulfonylurea, or pioglitazone plus metformin for type 2 diabetes using the Korean national health insurance claims database. The incidence of total CVD and individual outcomes of myocardial infarction (MI), heart failure (HF), and ischemic stroke (IS) were assessed using the hazard ratios (HRs) estimated from a Cox proportional-hazards model weighted for a propensity score.ResultsDuring follow-up, 3,881 patients developed a CVD, including 428 MIs, 212 HFs, and 1,487 ISs. The adjusted HR with 95% confidence interval (CI) for a sulfonylurea derivative plus metformin compared with a DPP-4 inhibitor plus metformin was 1.20 (1.09-1.32) for total CVD; 1.14 (1.04-1.91) for MI; 1.07 (0.71-1.62) for HF; and 1.51 (1.28-1.79) for IS. The HRs with 95% CI for total CVD, MI, HF, and IS for pioglitazone plus metformin were 0.89 (0.81-0.99), 1.05 (0.76-1.46), 4.81 (3.53-6.56), and 0.81 (0.67-0.99), respectively.ConclusionsCompared with a DPP-4 inhibitor plus metformin, treatment with a sulfonylurea drug plus metformin was associated with increased risks of total CVD, MI, and IS, whereas the use of pioglitazone plus metformin was associated with decreased total CVD and IS risks.     

Soluble interleukin-2 receptor serum level is a useful marker of hidradenitis suppurativa clinical staging

Hidradenitis suppurativa (HS) is a recurrent, debilitating suppurative skin disease. The major challenge is the choice of optimal treatment. Assessment of treatment effectiveness is currently associated with clinical observations of disease activity based on Hurley’s or Sartorius’ grading system. Detailed examination of patients with HS and evaluation of disease severity is frequently time-consuming and undoubtedly subjective. With regard to these factors, there is a need for laboratory findings that will help resolve the problem. The aim of this study was to determine the usefulness of soluble interleukin-2 receptor (sIL-2R) serum concentration as a marker of HS clinical staging and comparative analysis with the commonly conducted laboratory measurements, including white blood cell count, C-reactive protein and erythrocyte sedimentation rate. The statistical analysis of all these laboratory parameters conducted within a group of 54 individuals with HS revealed that sIL-2R serum level seems to be the most sensitive measurement for evaluation of disease stage. Moreover, the existence of strong dependences between sIL-2R serum concentration and Hurley’s HS grading system were demonstrated. In conclusion, we believe that sIL-2R serum level could be used as a valuable marker for disease staging in patients with HS.     

Disseminating the best available evidence: New challenges in public reporting of health care

As a direct benefit of the Health Care Reform Act (2010), concerted effort has been deployed to define and characterize the process by which the best available evidence for diagnosis or treatment intervention prognosis can be obtained. The science of research synthesis in health care has established the systematic research protocol by which randomized clinical trials and other clinical studies must be reviewed and compared for the level and quality of the evidence presented, as well as the consensus of the best available evidence synthesized and shared. This process of systematic review yields a reliable and valid approach in comparing different interventions and strategies to prevent, diagnose, treat and monitor health conditions in terms of efficacy, and or of effectiveness. The resulting bioinformation outcome of comparative effectiveness and efficacy research review of the available clinical data is expressed as a consensus of the best available evidence, which finds its way in evidence-based clinical practice guidelines, standards of care and eventually, in policies: hence, the acronym CEERAP (comparative effectiveness and efficacy review and policy). The methodological and the procedural criteria that determine and regulate the public reporting dissemination of this sort of bioinformation, and the extent of benefit to the patient's health literacy, which have remained a bit more elusive to this date, are investigated and discussed in this paper.     

Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes

Identifying the biochemical basis of microbial phenotypes is a main objective of comparative genomics. Here we present a novel method using multivariate machine learning techniques for comparing automatically derived metabolic reconstructions of sequenced genomes on a large scale. Applying our method to 266 genomes directly led to testable hypotheses such as the link between the potential of microorganisms to cause periodontal disease and their ability to degrade histidine, a link also supported by clinical studies.     

Clinical Outcomes in Low Risk Coronary Artery Disease Patients Treated with Different Limus-Based Drug-Eluting Stents - A Nationwide Retrospective Cohort Study Using Insurance Claims Database

The clinical outcomes of different limus-based drug-eluting stents (DES) in a real-world setting have not been well defined. The aim of this study was to investigate the clinical outcomes of three different limus-based DES, namely sirolimus-eluting stent (SES), Endeavor zotarolimus-eluting stent (E-ZES) and everolimus-eluting stent (EES), using a national insurance claims database. We identified all patients who received implantation of single SES, E-ZES or EES between January 1, 2007 and December 31, 2009 from the National Health Insurance claims database, Taiwan. Follow-up was through December 31, 2011 for all selected clinical outcomes. The primary end-point was all-cause mortality. Secondary end-points included acute coronary events, heart failure needing hospitalization, and cerebrovascular disease. Cox regression model adjusting for baseline characteristics was used to compare the relative risks of different outcomes among the three different limus-based DES. Totally, 6584 patients were evaluated (n=2142 for SES, n=3445 for E-ZES, and n=997 for EES). After adjusting for baseline characteristics, we found no statistically significant difference in the risk of all-cause mortality in three DES groups (adjusted hazard ratio [HR]: 1.14, 95% confidence interval [CI]: 0.94-1.38, p=0.20 in E-ZES group compared with SES group; adjusted HR: 0.77, 95% CI: 0.54-1.10, p=0.15 in EES group compared with SES group). Similarly, we found no difference in the three stent groups in risks of acute coronary events, heart failure needing hospitalization, and cerebrovascular disease. In conclusion, we observed no difference in all-cause mortality, acute coronary events, heart failure needing hospitalization, and cerebrovascular disease in patients treated with SES, E-ZES, and EES in a real-world population-based setting in Taiwan.     

Indirect Estimation of the Comparative Treatment Effect in Pharmacogenomic Subgroups

Evidence of clinical utility is a key issue in translating pharmacogenomics into clinical practice. Appropriately designed randomized controlled trials generally provide the most robust evidence of the clinical utility, but often only data from a pharmacogenomic association study are available. This paper details a method for reframing the results of pharmacogenomic association studies in terms of the comparative treatment effect for a pharmacogenomic subgroup to provide greater insight into the likely clinical utility of a pharmacogenomic marker, its’ likely cost effectiveness, and the value of undertaking the further (often expensive) research required for translation into clinical practice. The method is based on the law of total probability, which relates marginal and conditional probability. It takes as inputs: the prevalence of the pharmacogenomic marker in the patient group of interest, prognostic effect of the pharmacogenomic marker based on observational association studies, and the unstratified comparative treatment effect based on one or more conventional randomized controlled trials. The critical assumption is that of exchangeability across the included studies. The method is demonstrated using a case study of cytochrome P450 (CYP) 2C19 genotype and the anti-platelet agent clopidogrel. Indirect subgroup analysis provided insight into relationship between the clinical utility of genotyping CYP2C19 and the risk ratio of cardiovascular outcomes between CYP2C19 genotypes for individuals using clopidogrel. In this case study the indirect and direct estimates of the treatment effect for the cytochrome P450 2C19 subgroups were similar. In general, however, indirect estimates are likely to have substantially greater risk of bias than an equivalent direct estimate.     

Biological and clinical aspects of autoimmune inner ear disease.

The clinical presentation, diagnosis, and management of autoimmune inner ear disease are reviewed. Recent studies indicating an autoimmune etiology and pathogenesis are discussed, along with a comparative analysis of several promising new animal models. Further studies to define the natural history, pathogenesis, and diagnosis of the disease are suggested.     

PET/CT影像技术在神经退行性疾病动物模型研究中的应用

PET和CT影像技术是肿瘤、痴呆症、心脑血管病等的重要临床诊断技术,近年发展的小动物PET/CT成为对人类疾病动物模型,尤其是小动物模型进行比较医学研究的最新工具,能够活体无创的、动态的、定量的从分子水平观察动物的生理生化变化,进行代谢显像、受体显像、基因表达显像等。已经广泛应用于对神经退行性疾病的研究中.本文介绍了近年来一些小动物PET/CT在退行性疾病的研究中的最新应用。     

Biomonitoring using accessible human cells for exposure and health risk assessment

A major goal for genetic toxicologist is to provide precise information on exposure and health risk assessment for effective prevention of health problems. A frequently used approach for population study has been to utilize readily available blood cells (lymphocytes and red blood cells) as sentinel cell types to detect biological effects from exposure and to provide early warning signals for health risk. However, such approach still cannot be used reliably for developing strategies in risk assessment and disease prevention. It is possible that other available cell types which are more representative of the target cells for disease may be used to overcome the deficiency. In this report, the use of non-blood cells for biomonitoring is briefly reviewed. Their usefulness in certain exposure condition is highlighted and their effectiveness in documenting exposure compared with other cell types such as the traditional blood cells is presented. It is obvious that the decision in using these non-blood cells in biomonitoring is based on the exposure condition and the experimental design. Nevertheless, monitoring studies using non-blood cells should be encouraged with emphasis on providing dose–response information, comparative response with other cell types and effectiveness for health risk assessment.