Correction to: Do Limitations in the Design of PARADIGM-HF Justify the Slow Real World Uptake of Sacubitril/Valsartan (Entresto)?

The original version of this article unfortunately contained a mistake. There was a typo in the second sentence of the paragraph under the section Was the Dose of Drugs Fair?; "320 mg twice a day" should read "160mg twice a day". The corrected paragraph is shown below.

Do Health Care Delivery System Reforms Improve Value? The Jury Is Still Out.

BACKGROUND: Widespread restructuring of health delivery systems is underway in the United States to reduce costs and improve the quality of health care. OBJECTIVE: To describe studies evaluating the impact of system-level interventions (incentives and delivery structures) on the value of US health care, defined as the balance between quality and cost. RESEARCH DESIGN: We identified articles in PubMed (2003 to July 2014) using keywords identified through an iterative process, with reference and author tracking. We searched tables of contents of relevant journals from August 2014 through 11 August 2015 to update our sample. SUBJECTS: We included prospective or retrospective studies of system-level changes, with a control, reporting both quality and either cost or utilization of resources. MEASURES: Data about study design, study quality, and outcomes was extracted by one reviewer and checked by a second. RESULTS: Thirty reports of 28 interventions were included. Interventions included patient-centered medical home implementations (n=12), pay-for-performance programs (n=10), and mixed interventions (n=6); no other intervention types were identified. Most reports (n=19) described both cost and utilization outcomes. Quality, cost, and utilization outcomes varied widely; many improvements were small and process outcomes predominated. Improved value (improved quality with stable or lower cost/utilization or stable quality with lower cost/utilization) was seen in 23 reports; 1 showed decreased value, and 6 showed unchanged, unclear, or mixed results.Study limitations included variability among specific endpoints reported, inconsistent methodologies, and lack of full adjustment in some observational trials. Lack of standardized MeSH terms was also a challenge in the search. CONCLUSIONS: On balance, the literature suggests that health system reforms can improve value. However, this finding is tempered by the varying outcomes evaluated across studies with little documented improvement in outcome quality measures. Standardized measures of value would facilitate assessment of the impact of interventions across studies and better estimates of the broad impact of system change.

Primary outcome switching among drug trials with and without principal investigator financial ties to industry: a cross-sectional study.

OBJECTIVES: To determine the relationship between manufacturer-related financial ties among investigators of published drug trials and rates of discrepant registered and published primary trial outcomes. DESIGN: Cross-sectional study. SETTING: Human subjects drug trials published in 'core clinical' MEDLINE journals in 2013. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary study endpoint was the presence of a prospectively registered, clearly defined primary outcome that matched the published primary outcome for each included trial. Secondary outcomes included assessments of registration timing and quality, and the impact of outcome discrepancies between registration and publication on the statistical significance of the included trials. RESULTS: Of 192 included trials, 134 (70%) were positive and 58 (30%) were negative. Financial ties were present between first or last authors and drug manufacturers for 130 trials (68%), of which 78% were positive, versus 53% of trials with no financial ties that were positive. Clearly defined, prospectively registered outcomes that matched the published outcomes were present in just 76 of the 192 trials (40%). After adjusting for study start date and sample size, the observed relationship between investigator financial ties and the presence of a match between prospectively registered and published primary outcomes was of borderline statistical significance (OR 2.12, 95% CI 0.998 to 4.50). Studies with financial ties present were more likely than studies without ties to have been prospectively registered (78%vs48%, P<0.001) and were more likely to have prospectively registered a clearly defined primary outcome(62%vs35%, P<0.001). CONCLUSIONS: Less than half of the trials in this cohort were prospectively registered with a clear primary outcome that was consistent with the primary outcome reported in the published manuscript. The presence of investigator financial ties was associated with higher quality registration practices, though this association diminished after adjusting for factors that impact registration quality.

Financial ties of principal investigators and randomized controlled trial outcomes: cross sectional study.

OBJECTIVE:  To examine the association between the presence of individual principal investigators' financial ties to the manufacturer of the study drug and the trial's outcomes after accounting for source of research funding. DESIGN:  Cross sectional study of randomized controlled trials (RCTs). SETTING:  Studies published in "core clinical" journals, as identified by Medline, between 1 January 2013 and 31 December 2013. PARTICIPANTS:  Random sample of RCTs focused on drug efficacy. MAIN OUTCOME MEASURE:  Association between financial ties of principal investigators and study outcome. RESULTS:  A total of 190 papers describing 195 studies met inclusion criteria. Financial ties between principal investigators and the pharmaceutical industry were present in 132 (67.7%) studies. Of 397 principal investigators, 231 (58%) had financial ties and 166 (42%) did not. Of all principal investigators, 156 (39%) reported advisor/consultancy payments, 81 (20%) reported speakers' fees, 81 (20%) reported unspecified financial ties, 52 (13%) reported honorariums, 52 (13%) reported employee relationships, 52 (13%) reported travel fees, 41 (10%) reported stock ownership, and 20 (5%) reported having a patent related to the study drug. The prevalence of financial ties of principal investigators was 76% (103/136) among positive studies and 49% (29/59) among negative studies. In unadjusted analyses, the presence of a financial tie was associated with a positive study outcome (odds ratio 3.23, 95% confidence interval 1.7 to 6.1). In the primary multivariate analysis, a financial tie was significantly associated with positive RCT outcome after adjustment for the study funding source (odds ratio 3.57 (1.7 to 7.7). The secondary analysis controlled for additional RCT characteristics such as study phase, sample size, country of first authors, specialty, trial registration, study design, type of analysis, comparator, and outcome measure. These characteristics did not appreciably affect the relation between financial ties and study outcomes (odds ratio 3.37, 1.4 to 7.9). CONCLUSIONS:  Financial ties of principal investigators were independently associated with positive clinical trial results. These findings may be suggestive of bias in the evidence base.

Common Reasons That Asymptomatic Patients Who Are 65 Years and Older Receive Carotid Imaging.

IMPORTANCE: National guidelines do not agree on the role of carotid screening in asymptomatic patients (ie, patients who have not had a stroke or transient ischemic attack). Recently, several physician organizations participating in the Choosing Wisely campaign have identified carotid imaging in selected asymptomatic populations as being of low value. However, the majority of patients who are evaluated for carotid stenosis and subsequently revascularized are asymptomatic. OBJECTIVE: To better understand why asymptomatic patients who undergo revascularization receive initial carotid imaging. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study of 4127 Veterans Health Administration patients 65 years and older undergoing carotid revascularization for asymptomatic carotid stenosis between 2005 and 2009. MAIN OUTCOMES AND MEASURES: Indications for carotid ultrasounds were extracted using trained abstractors. Frequency of indications and appropriateness of initial carotid ultrasound imaging for patients within each rating category after the intervention were reported. RESULTS: The mean (SD) age of this cohort of 4127 patients was 73.6 (5.9) years; 4014 (98.8%) were male. Overall, there were 5226 indications for 4063 carotid ultrasounds. The most common indications listed were carotid bruit (1578 [30.2% of indications]) and follow-up for carotid disease (stenosis/history of carotid disease) in patients who had previously documented carotid stenosis (1087 [20.8% of indications]). Multiple vascular risk factors were the next most common indication listed. Rates of appropriate, uncertain, and inappropriate imaging were 5.4% (227 indications), 83.4% (3387 indications), and 11.3% (458 indications), respectively. Among the most common inappropriate indications were dizziness/vertigo and syncope. Among the 4063 patients, 3373 (83.0%) received a carotid endarterectomy. Overall, 663 procedures were performed in patients 80 years and older. CONCLUSIONS AND RELEVANCE: Carotid bruit and follow-up for carotid disease accounted for approximately half of all indications provided by physicians for carotid testing. Strong consideration should be given to improving the evidence base around carotid testing, especially around monitoring stenosis over long periods and evaluating carotid bruits. Targeting carotid ultrasound ordering with decision support tools may also be an important step in reducing use of low-value imaging.