Implications Of Comparative Effectiveness Research Research Articles

Unanticipated Effects of New Drug Availability on Antiretroviral Durability: Implications for Comparative Effectiveness Research.

Background. Durability of antiretroviral (ARV) therapy is associated with improved human immunodeficiency virus (HIV) outcomes. Data on ARV regimen durability in recent years and clinical settings are lacking.Methods. This retrospective follow-up study included treatment-naive HIV-infected patients initiating ARV therapy between January 2007 and December 2012 in a university-affiliated HIV clinic in the Southeastern United States. Outcome of interest was durability (time to discontinuation) of the initial regimen. Durability was evaluated using Kaplan-Meier survival analyses. Cox proportional hazard analyses was used to evaluate the association among durability and sociodemographic, clinical, and regimen-level factors.Results. Overall, 546 patients were analyzed. Median durability of all regimens was 39.5 months (95% confidence interval, 34.1–44.4). Commonly prescribed regimens were emtricitabine and tenofovir with efavirenz (51%; median duration = 40.1 months) and with raltegravir (14%; 47.8 months). Overall, 67% of patients had an undetectable viral load at the time of regimen cessation. Discontinuation was less likely with an integrase strand transfer inhibitor (adjusted hazards ratio [aHR] = 0.35, P = .001) or protease inhibitor-based regimen (aHR = 0.45, P = .006) and more likely with a higher pill burden (aHR = 2.25, P = .003) and a later treatment era (aHR = 1.64, P < .001).Conclusions. Initial ARV regimen longevity declined in recent years contemporaneous with the availability of several new ARV drugs and combinations. Reduced durability mostly results from a preference for newly approved regimens rather than indicating failing therapy, as indicated by viral suppression observed in a majority of patients (67%) prior to regimen cessation. Durability is influenced by extrinsic factors including new drug availability and provider preference. Medication durability must be interpreted carefully in the context of a dynamic treatment landscape.

Co-calibrating quality-of-life scores from three pulmonary disorders: implications for comparative-effectiveness research

Background Efficient use of health resources requires accurate outcome assessment. Disease-specific patient-reported outcome (PRO) measures are designed to be highly relevant to patients with a specific disease. They have advantages over generic PROs that lack relevance to patient groups and miss crucial impacts of illness. It is thought that disease-specific measurement cannot be used in comparative effectiveness research (CER). The present study provides further evidence of the value of disease-specific measures in making valid comparisons across diseases.Methods The Asthma Life Impact Scale (ALIS, 22 items), Living with Chronic Obstructive Pulmonary Disease (LCOPD, 22 items) scale, and Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR, 25 items) were completed by 140, 162, and 91 patients, respectively. The three samples were analyzed for fit to the Rasch model, then combined into a scale consisting of 58 unique items and re-analyzed. Raw scores on the three measures were co-calibrated and a transformation table produced.Results The scales fit the Rasch model individually (ALIS Chi2 probability value (p-Chi2) = 0.05; LCOPD p-Chi2 = 0.38; CAMPHOR p-Chi2 = 0.92). The combined data also fit the Rasch model (p-Chi2 = 0.22). There was no differential item functioning related to age, gender, or disease. The co-calibrated scales successfully distinguished between perceived severity groups (p < 0.001).Limitations The samples were drawn from different sources. For scales to be co-calibrated using a common item design, they must be based on the same theoretical construct, be unidimensional, and have overlapping items.Conclusions The results showed that it is possible to co-calibrate scores from disease-specific PRO measures. This will permit more accurate and sensitive outcome measurement to be incorporated into CER. The co-calibration of needs-based disease-specific measures allows the calculation of γ scores that can be used to compare directly the impact of any type of interventions on any diseases included in the co-calibration.

Circulation : Clinical Summaries

<i>Circulation</i> : Clinical Summaries

The Evolution of Self-Reported Urinary and Sexual Dysfunction over the Last Two Decades: Implications for Comparative Effectiveness Research

BackgroundDespite the paramount importance of patient-reported outcomes, little is known about the evolution of patient-reported urinary and sexual function over time. ObjectiveTo evaluate differences in pretreatment urinary and sexual function in two population-based cohorts of men with prostate cancer enrolled nearly 20 yr apart. Design, setting, and participantsPatients were enrolled in the Prostate Cancer Outcomes Study (PCOS) or the Comparative Effectiveness Analysis of Surgery and Radiation (CEASAR) study, two population-based cohorts that enrolled patients with incident prostate cancer from 1994 to 1995 and from 2011 to 2012, respectively. Participants completed surveys at baseline and various time points thereafter. Outcome measurements and statistical analysisWe performed multivariable logistic and linear regression analysis to investigate differences in pretreatment function between studies. Results and limitationsThe study comprised 5469 men of whom 2334 (43%) were enrolled in PCOS and 3135 (57%) were enrolled in CEASAR. Self-reported urinary incontinence was higher in CEASAR compared with PCOS (7.7% vs 4.7%; adjusted odds ratio [OR]: 1.83; 95% confidence interval [CI], 1.39–2.43). Similarly, self-reported erectile dysfunction was more common among CEASAR participants (44.7% vs 24.0%) with an adjusted OR of 3.12 (95% CI, 2.68–3.64). Multivariable linear regression models revealed less favorable self-reported baseline function among CEASAR participants in the urinary incontinence and sexual function domains. The study is limited by its observational design and possibility of unmeasured confounding. ConclusionsReporting of pretreatment urinary incontinence and erectile dysfunction has increased over the past two decades. These findings may reflect sociological changes including heightened media attention and direct-to-consumer marketing, among other potential explanations. Patient summaryPatient reporting of urinary and sexual function has evolved and is likely contingent on continually changing societal norms. Recognizing the evolving nature of patient reporting is essential in efforts to conduct high-quality, impactful comparative effectiveness research.

Changing patterns of use of osteoporosis medications in the years after launch: implications for comparative effectiveness research

Newly marketed medications may be used selectively in patients with more severe disease. Changes in patterns of use following a drug's introduction to the market can greatly influence results from non-experimental comparative effectiveness research. We sought to explore this issue by characterizing trends in oral and injectable prescription drug claims for the prevention and treatment of osteoporosis. We examined a post-menopausal population of women age 55 years and older in the Truven Health Analytics MarketScan® Databases. We used propensity score (PS) methods to describe how predictors of new users of oral and injectable osteoporosis medications change over time. We found that injectable osteoporosis medications tended to be used more selectively in the higher risk patients shortly after launch. Over time, they appeared to be used increasingly in lower risk patients. If disease severity is incompletely captured in the data, comparative effectiveness of novel osteoporosis medications may be difficult to accurately estimate, particularly when medications are new to market.

Treatment Dynamics of Newly Marketed Drugs and Implications for Comparative Effectiveness Research

ObjectivesClinicians and payers require rapid comparative effectiveness (CE) evidence generation to inform decisions for new drugs. We empirically assessed treatment dynamics of newly marked drugs and their implications for conducting CE research. MethodsWe used claims data to evaluate five drug-outcome pairs: 1) raloxifene (vs. alendronate) and fracture; 2) risedronate (vs. alendronate) and fracture; 3) simvastatin plus ezetimibe fixed-dose combination (simvastatin + ezetimibe) (vs. simvastatin alone) and cardiovascular events; 4) rofecoxib (vs. nonselective nonsteroidal anti-inflammatory drugs [ns-NSAIDs]) and myocardial infarction; and 5) rofecoxib (vs. ns-NSAIDS) and gastrointestinal bleed. We examined utilization dynamics in the early marketing period, including evolving utilization patterns, outcome risk among those treated with new versus established drugs, and prior treatment patterns that may indicate treatment resistance or intolerance. We addressed these challenges by replicating active CE monitoring with sequential matched cohort analysis. ResultsPatients initiating new drugs were more likely to have used other drugs for the same indication in the past, but the majority of patients in all new drug cohorts were treatment naive (82.0% overall). Patients initiating rofecoxib had higher predicted baseline risk of gastrointestinal bleed than did patients initiating ns-NSAIDs. Patients initiating risedronate and alendronate had similar predicted baseline risks of fracture, while those initiating raloxifene and simvastatin + ezetimibe had lower risks of outcomes of interest relative to their comparators. Prospective monitoring yielded results consistent with expectation for each example. ConclusionsMany challenges to assessing the CE of new drugs are borne out in empirical data. Attention to these challenges can yield valid CE results.

Comparative Effectiveness Research Paradigm: Implications for Systematic Reviews and Clinical Practice Guidelines

The objectives of this article are (1) to examine the similarities and differences between comparative effectiveness research (CER) and evidence-based medicine (EBM); (2) to describe the implications of CER for systematic review methodologies in oncology; and (3) to address the transition from systematic reviews to guideline development and the implications of CER in this process. An analysis of the principles and methods of CER was undertaken in light of EBM, systematic reviews, and guidelines. There is considerable overlap between the principles and methods of the two paradigms. The focus on best care options in the context of routine practice is a more central tenet of the CER paradigm. Thus, its value is not that it is the first paradigm to recognize the importance of a patient-focused approach in the research community, but rather, given the attention it has garnered, the CER paradigm may be precisely the reminder and push required to: one, influence how systematic questions are framed so that a more patient-relevant perspective is achieved; two, broaden the types of study designs that are valued and to include those, such as pragmatic trials and observational studies, that are better able to answer effectiveness questions; three, accelerate the development and application of statistical methods that enable indirect comparisons of cancer care options; and four, create clinical practice guidelines that are better positioned to improve quality of care and system performance. Over time, we will see if the CER paradigm lives up to its potential.

PSU30 A Systematic Review of the Use of Patient-Centered Outcome Measures in Studies of Spinal Fusion Surgery for Degenerative Disc Disease: Implications for Comparative Effectiveness Research

PSU30 A Systematic Review of the Use of Patient-Centered Outcome Measures in Studies of Spinal Fusion Surgery for Degenerative Disc Disease: Implications for Comparative Effectiveness Research

Comparative Effectiveness Research in the Regulatory Setting

Consumers today have access to more information regarding everyday decisions than ever before. Healthcare is no exception. The US health reform laws signed in March 2010, provided a vehicle for systematically facilitating the application of this trend to the US healthcare system through the creation of an independent, government-funded institute, whose purpose is to advance the understanding of which treatments and approaches to healthcare work best for which patients. This article discusses the implications of comparative effectiveness research (CER) for governments, industry, healthcare systems, clinicians and patients. Properly developed and applied information derived from CER can help establish the value of medicines, procedures and services, and promote a more qualityfocused, cost-effective healthcare system. However, much uncertainty remains that centres on precisely how this information will be used. Recently, many patient groups, physicians and biopharmaceutical companies have raised concerns that CER might have the unintended consequences of restricting access to treatments. These effects must be weighed carefully when considering whether comparative effectiveness data should become a prerequisite for US FDA submissions. The process of designing and implementing comparative clinical trials at such an early stage in product development poses numerous challenges including dose selection, use of marketed comparators (which may lead to consumer bias and increased patient dropout rates), physician comfort and experience (for medical devices), and endpoint selection, among others, and could delay introduction of new therapies. In addition, ‘over-interpretation’ of early comparative data could lead to an underappreciation of benefits in patient subgroups and an undervaluation of incremental innovation. Thus, a requirement for premarketing comparative studies could prove not only to create a costly disincentive to invest in developing therapies, but could also have a detrimental impact on their development. Regardless of how information is provided to patients and healthcare decision-makers, it should be gathered in a manner that does not delay patient access to new technologies nor hamper innovation. The desire to provide consumers with more information regarding choice is well intentioned; however, patient care and satisfaction should always remain the foremost concern when discussing the implementation of new policies in the healthcare field.

Survival Benefit With Drug-Eluting Stents in Observational Studies

Recently, there has been increased interest in leveraging observational studies for comparative effectiveness research. Without robust and valid risk adjustment, however, findings from these nonrandomized studies may remain biased. Previous studies examining long-term mortality with drug-eluting stents (DESs) have demonstrated discordant results between randomized trials and observational studies. To examine the impact of treatment selection bias on these findings, we used data from a prospective percutaneous coronary intervention (PCI) registry (EVENT [Evaluation of Drug Eluting Stents and Ischemic Events]) to compare clinical outcomes between DESs and bare metal stents (BMSs) using conventional (multivariable regression and propensity matching) and novel (instrumental variable analysis) risk-adjustment techniques. The study population consisted of 9266 patients who underwent nonemergent PCI with stent placement at 55 US centers between 2004 and 2007. All-cause mortality and target lesion revascularization (TLR) were assessed prospectively over 1 year of follow-up. Overall, 8171 patients (88%) received DES, but this proportion substantially differed by treatment year (93% in 2004-2006 and 73% in 2007; P<0.001). One-year rates of death and TLR were significantly lower with DES versus BMS (death, 2.5% versus 5.6%; TLR, 4.2% versus 6.9%; P<0.001 for both), findings that persisted in both multivariable-adjusted and propensity-matched analyses. In contrast, instrumental variable analysis, using enrollment period (2004-2006 versus 2007) as the instrument, demonstrated no significant difference in 1-year mortality (predicted absolute difference, 2.0%; 95% CI, -1.8% to 5.7%; P=0.30) and a strong trend toward reduced TLR with DES use (predicted absolute difference, -4.2%; 95% CI, -8.8% to 0.4%; P=0.07). Among unselected PCI patients in contemporary practice, DES use tended to be associated with a consistent reduction in TLR regardless of risk-adjustment method but showed discordant effects on mortality with conventional risk adjustment compared with instrumentable variable analysis. These findings underscore the limitations of standard risk-adjustment methods to adequately address treatment selection bias in nonrandomized studies and have important implications for comparative effectiveness research using observational data.

The Implications of Comparative Effectiveness Research for Academic Medicine

With growing constraints on government spending, policy makers are investing in comparative effectiveness research (CER) to attempt to bring the power of science to bear on the problems of suboptimal outcomes and high cost in the U.S. health care system. This commitment of resources to CER reflects confidence that better evidence can help clinicians and patients make better decisions, consistent with the long tradition of medical schools' and teaching hospitals' use of science to inform medical care. Thus, CER offers a great opportunity, albeit with some considerable challenges, for academic medicine to play a central role in comprehensive health care reform. Certainly, many scientists conducting CER will learn their methodological rigor in the training programs of academic health centers. Numerous new CER research teams will be needed, establishing effective partnerships far outside the walls of the traditional academic setting. And the clinicians interpreting the medical literature and applying the insights from CER to the unique problems of individual patients will need to learn this evidence-based, patient-centered care from the educators, mentors, and role models at U.S. medical and other health science schools and teaching hospitals. Achieving this will require investment in research infrastructure, adaptations of institutional culture, development of new disciplines and research methods, establishment of new collaborations, training of new faculty, and the expansion and refocusing of educational capacity. By successfully responding to this challenge, academic medicine can further strengthen its long-standing commitment to the scientific practice of medicine and the use of evidence in patient-centered, personalized care.

Implications of comparative effectiveness research for radiation oncology

PurposeThe essence of comparative effectiveness research (CER) is to understand what health interventions work, for which patients, and under what conditions. The objective of this article is to introduce the relative strengths and weaknesses of several forms of evidence to illustrate the potential for CER evidence generation within radiation oncology. MethodsWe introduce the underlying concepts of effectiveness and efficacy. We describe the design of traditional explanatory randomized trials (RCTs). We introduce the rationale, strengths, and weaknesses of several alternative study designs for comparative effectiveness, including pragmatic clinical trials, adaptive trials, and observational (nonrandomized) studies. ResultsExplanatory RCTs are designed to assess the efficacy of an intervention while achieving a high degree of internal validity. Pragmatic clinical trials (PCTs) are prospective studies performed in typical, real-world clinical practice settings. The emphasis of PCTs is to maintain a degree of internal validity while also maximizing external validity. Adaptive trials can be modified at interim stages using existing or evolving evidence in the course of a trial, which may allow trials to maintain clinical relevance by studying current treatments. Observational data are becoming increasingly important, given substantial funding for clinical registries and greater availability of electronic medical records and claims databases, but need to address well-known limitations such as selection bias. ConclusionWith the rapid proliferation of new and evolving radiotherapy technologies, it is incumbent upon our field to invest in building the evidence base for radiotherapy CER and to actively participate in current initiatives for generating comparative evidence.

Scientific and Organizational Collaboration in Comparative Effectiveness Research: The VA Cooperative Studies Program Model

Comparative effectiveness research (CER) has the ability to improve health and inform patients, clinicians, and decision makers. However, calls for more devoted efforts with regard to CER have been countered by methodological, resource, and translational challenges related to conducting these studies. The Department of Veterans Affairs (VA) Cooperative Studies Program (CSP) is a clinical research infrastructure that has contributed much evidence to support clinical practice for several decades. Although the CSP does not exclusively focus on CER, it employs strategies that lend themselves toward the planning and execution of studies that seek to compare interventions and/or strategies for treating disease. Consequently, the CSP provides a model for addressing important scientific, structural, and operational factors for clinical research, including large, national and multinational comparative effectiveness studies. Exploration of the difficulties the CSP has encountered can help to elucidate barriers that face CER. This article discusses factors and approaches for collaboratively developing and conducting definitive studies that produce outcomes aimed at influencing clinical practice, lessons that have resulted from such efforts, and ongoing challenges. Future program directions are also presented to highlight areas of emphasis and implications for CER within the VA and nationally.

Addressing “Waste” in Diagnostic Imaging: Some Implications of Comparative Effectiveness Research

Comparative effectiveness research is intended to provide evidence to improve patient outcomes through the use of the most appropriate health technology affordable. The authors present 5 case studies, focusing on the use of plain radiography in common clinical scenarios, to illustrate the considerable scope for comparative effectiveness research within medical imaging and the different levels of evidence currently in existence to guide the improved use of medical imaging. These are blunt ankle injury, breast cancer follow-up, low back pain, routine daily chest x-rays in intensive care, and screening for breast cancer. Although there are established models for evaluating new technologies, especially pharmaceuticals, against the most commonly used current technology, the evaluation of technologies in current clinical practice is in an early phase of development. Because evaluation resources are limited, one major challenge is developing ways to identify established technologies for evaluation to refine the indications for their use. A set of criteria with which to identify established technologies that may not be delivering value for money is described, and their use is illustrated in relation to the 5 case studies. These criteria could be incorporated into literature search strategies, stakeholder consultations, and utilization scanning. Once identified, these technologies should be formally evaluated for their performance in improving patient health without restricting the availability of other effective interventions.