Clinical Evidence Generation Research Articles

Clinical evidence inputs to comparative effectiveness research could impact the development of novel treatments.

This study aims to analyze the impacts of a range of clinical evidence generation scenarios associated with comparative effectiveness research (CER) on pharmaceutical innovation. We used the Global Pharmaceutical Policy Model to project the effect of changes in pharmaceutical producer costs, revenues and timings on drug innovation and health for the age 55+ populations in the USA and Europe through year 2060 using three clinical scenarios. Changes in producer incentives from widespread CER evidence generation and use had varied but often large predicted impacts on simulated outcomes in 2060. Effect on the number of new drug introductions ranged from a 81.1% reduction to a 45.5% increase, and the effect on population-level life expectancy ranged from a 15.6% reduction to a 11.4% increase compared to baseline estimates. The uncertainty surrounding the consequences of increased clinical evidence generation and use on innovation calls for a carefully measured approach to CER implementation, balancing near-term benefits to spending and health with long-term implications for innovation.

Translation of acute coronary syndrome therapies: From evidence to routine clinical practice

The use of evidence-based therapies has improved the outcome of patients with acute coronary syndrome (ACS), but there is a time lag between the generation of clinical evidence and its application in routine clinical practice. We sought to quantify temporal lags in the lifecycle of American College of Cardiology (ACC)/American Heart Association (AHA) class IA ACS therapies. Using current and historical ACC/AHA guideline publications, we retrieved publication dates of pivotal clinical trials (PCTs) and class IA guideline-recommended therapies for patients with ST-elevation myocardial infarction (STEMI) and unstable angina (UA)/non-STEMI (NSTEMI). Clinical practice uptake data for each therapy were retrieved from the National Registry for Myocardial Infarction, Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the ACC/AHA Guidelines, and Acute Coronary Treatment and Intervention Outcomes Network Registry-Get with the Guidelines, which are registries containing publicly available peer-reviewed data. Descriptive data were calculated and compared for each phase of the evidence lifecycle for both STEMI and UA/NSTEMI drug classifications. We identified 11 class IA- and 4 class IB/IC-recommended therapies for acute, inhospital, and discharge use for patients with STEMI or UA/NSTEMI. The median time lags were 2 years (interquartile range [IQR], 1-4 years) from PCT to practice guideline recommendation, 14 years (IQR, 11-15 years) from guideline recommendation to 90% practice uptake, and overall, a 16-year median (IQR, 13-19 years) from PCT to 90% practice uptake. The time of PCT publication to meaningful uptake of class IA ACS therapies into clinical practice took a median of 16 years. This significant time lag indicates systemic barriers to the translation of therapeutics into routine clinical practice.

How good is "evidence" from clinical studies of drug effects and why might such evidence fail in the prediction of the clinical utility of drugs?

Promising evidence from clinical studies of drug effects does not always translate to improvements in patient outcomes. In this review, we discuss why early evidence is often ill suited to the task of predicting the clinical utility of drugs. The current gap between initially described drug effects and their subsequent clinical utility results from deficits in the design, conduct, analysis, reporting, and synthesis of clinical studies-often creating conditions that generate favorable, but ultimately incorrect, conclusions regarding drug effects. There are potential solutions that could improve the relevance of clinical evidence in predicting the real-world effectiveness of drugs. What is needed is a new emphasis on clinical utility, with nonconflicted entities playing a greater role in the generation, synthesis, and interpretation of clinical evidence. Clinical studies should adopt strong design features, reflect clinical practice, and evaluate outcomes and comparisons that are meaningful to patients. Transformative changes to the research agenda may generate more meaningful and accurate evidence on drug effects to guide clinical decision making.

Evidence Requirements for Innovative Imaging Devices: From Concept to Adoption

Changes in the regulatory and reimbursement environment for advances in imaging in the United States are leading to increasing requirements for formal clinical evidence of efficacy, effectiveness, and safety. The authors describe 5 phases of an imaging product's lifecycle: design, regulatory clearance and approval, early adoption, reimbursement, and full adoption. Each phase has distinct needs for clinical evidence. With increasing costs of clinical evidence generation, the question of ownership of the responsibility to gather clinical evidence at each successive phase becomes important. Mismatch between the pace of advances in imaging technologies and the time required to do formal clinical trials to clear regulatory and reimbursement evidence requirements threatens patient access to the benefits of innovation such as reduction in exposure to radiation. Public and payer requirements for clinical evidence must also be evaluated for their impact on incremental design improvements, which have historically characterized advances in diagnostic imaging.

Academic Medical Centers and Financial Conflicts of Interest

and prespecified secondary analyses that accounted for intersite variation in compliance, may have provided insight into the failure to detect a difference in mortality. Information on steps taken to ensure compliance would also be helpful should there be attempts to disseminate higher PEEP strategies to clinical practice. In summary, despite the relatively straightforward physiologic basis for the individualized titration of the “best” PEEP, generation of robust clinical evidence in its favor is bedeviled by a number of complicated study design choices and implications. Issues largely solved for placebo-controlled drug trials resurface when testing these complex interventions. Nevertheless, both the Lung Open Ventilation Study and the Express Study demonstrated that it was possible to convert the physiologic principles on which experts base their care into a set of reproducible instructions and then test these instructions in a broad multicenter environment. Although neither study demonstrated a significant improvement in mortality, their findings appear to have implications for future practice. Finally, these studies made important steps toward increasingly rigorous assessment of increasingly sophisticated protocols for the best care of critically ill patients.