Intravascular Microaxial Left Ventricular Assist Device Manufacturer Payments to Cardiologists and Use of Devices.

This study examines whether payments from a left ventricular assist device manufacturer to cardiologists performing percutaneous coronary intervention were associated with any use of the devices.

Prices and complications in hospital-based and freestanding surgery centers.

OBJECTIVES: To quantify differences in prices paid and procedural complications incurred in hospital outpatient departments (HOPDs) and freestanding ambulatory surgery centers (ASCs). STUDY DESIGN: Observational study using deidentified 2019-2020 insurance claims from Blue Cross Blue Shield insurance plans nationally, with information on prices paid and complications incurred for colonoscopy, knee or shoulder arthroscopy, and cataract removal surgery. METHODS: The data include 1,662,183 patients who received a colonoscopy, 53.5% of whom were treated in HOPDs; 259,200 patients who underwent arthroscopy, 61.0% of whom were treated in HOPDs; and 173,664 patients who had cataract removal surgery, 34.7% of whom were treated in HOPDs. Multivariable linear regression methods were used to identify the associations between HOPD and ASC site of care, prices, and complications after adjusting for patient demographics, risk, and geographic market location. RESULTS: After adjusting for patient characteristics, risk, and geographic market location, prices paid in HOPDs were 54.9% higher than those charged in ASCs for colonoscopy (95% CI, 53.6%-56.1%), 44.4% higher for arthroscopy (95% CI, 43.0%-45.8%), and 44.0% higher for cataract removal surgery (95% CI, 42.9%-45.5%). Adjusted rates of complications were slightly higher in HOPDs than ASCs for colonoscopy over a 90-day interval but similar over the 7- and 30-day intervals. Rates were statistically and clinically similar between the 2 sites of care for arthroscopy and cataract removal. CONCLUSIONS: The higher prices charged in HOPDs for the 3 ambulatory procedures were not balanced by better quality-as measured by rates of procedural complications-compared with procedures performed in nonhospital ASCs.

Informational letters or postcards to initiate remote monitoring among veterans with pacemakers and implantable cardioverter-defibrillators: A randomized, controlled trial.

BACKGROUND: Remote monitoring (RM) of pacemakers and implantable cardioverter-defibrillators (ICDs) is a Class 1, Level of Evidence A recommendation because of its multitude of clinical benefits. However, RM adherence rates are suboptimal, precluding patients from achieving these benefits. There is a need for direct-to-patient efforts to improve adherence. METHODS: In this national randomized, controlled trial conducted in the Veterans Health Administration (VHA), 2120 patients with a pacemaker or ICD who had not sent an RM transmission for ≥1 year (and usually ≥3 years) while under VHA care for their device were randomly assigned to be mailed a postcard (n = 1076) or a detailed letter (n = 1044). The postcard described what RM does and its key benefits (reduced mortality and fewer in-person visits). The letter provided a similar message but included more details about RM benefits and the process. The primary outcome was an RM transmission sent within 90 days of mailing, and a secondary outcome was an RM transmission sent within 365 days. RESULTS: The primary outcome was achieved in 121 (11.3%) in the postcard and 96 patients (9.2%) in the letter group (p = .12). The secondary outcome was achieved in 266 (24.7%) and 239 (22.9%), respectively (p = .32). CONCLUSIONS: This randomized trial showed no significant difference in the proportion of chronically non-adherent patients who sent an RM transmission after receiving a low-cost postcard or a detailed, higher-cost letter encouraging their participation in RM. However, as only a minority of patients responded to either, further work is needed to engage patients in the life-saving benefits of RM.

Use of Electronic Health Records to Characterize Patients with Uncontrolled Hypertension in Two Large Health System Networks.

Background: Improving hypertension control is a public health priority. However, consistent identification of uncontrolled hypertension using computable definitions in electronic health records (EHR) across health systems remains uncertain. Methods: In this retrospective cohort study, we applied two computable definitions to the EHR data to identify patients with controlled and uncontrolled hypertension and to evaluate differences in characteristics, treatment, and clinical outcomes between these patient populations. We included adult patients (≥ 18 years) with hypertension receiving ambulatory care within Yale-New Haven Health System (YNHHS; a large US health system) and OneFlorida Clinical Research Consortium (OneFlorida; a Clinical Research Network comprised of 16 health systems) between October 2015 and December 2018. We identified patients with controlled and uncontrolled hypertension based on either a single blood pressure (BP) measurement from a randomly selected visit or all BP measurements recorded between hypertension identification and the randomly selected visit). Results: Overall, 253,207 and 182,827 adults at YNHHS and OneFlorida were identified as having hypertension. Of these patients, 83.1% at YNHHS and 76.8% at OneFlorida were identified using ICD-10-CM codes, whereas 16.9% and 23.2%, respectively, were identified using elevated BP measurements (≥ 140/90 mmHg). Uncontrolled hypertension was observed among 32.5% and 43.7% of patients at YNHHS and OneFlorida, respectively. Uncontrolled hypertension was disproportionately higher among Black patients when compared with White patients (38.9% versus 31.5% in YNHHS; p < 0.001; 49.7% versus 41.2% in OneFlorida; p < 0.001). Medication prescription for hypertension management was more common in patients with uncontrolled hypertension when compared with those with controlled hypertension (overall treatment rate: 39.3% versus 37.3% in YNHHS; p = 0.04; 42.2% versus 34.8% in OneFlorida; p < 0.001). Patients with controlled and uncontrolled hypertension had similar rates of short-term (at 3 and 6 months) and long-term (at 12 and 24 months) clinical outcomes. The two computable definitions generated consistent results. Conclusions: Our findings illustrate the potential of leveraging EHR data, employing computable definitions, to conduct effective digital population surveillance in the realm of hypertension management.

Monitoring of Remotely Reprogrammable Implantable Loop Recorders With Algorithms to Reduce False-Positive Alerts.

BACKGROUND: Implantable loop recorders (ILRs) are increasingly placed for arrhythmia detection. However, historically, ≈75% of ILR alerts are false positives, requiring significant time and effort for adjudication. The LINQII and LUX-Dx are remotely reprogrammable ILRs with dual-stage algorithms using artificial intelligence to reduce false positives, but their utility in routine clinical practice has not been studied. METHODS AND RESULTS: We identified patients with the LINQII and LUX-Dx who were monitored by the Veterans Affairs National Cardiac Device Surveillance Program between March and June 2022. ILR programming was customized on the basis of implant indication. All alerts and every 90-day scheduled transmissions were manually reviewed. ILRs were remotely reprogrammed, as appropriate, after false-positive alerts or 2 consecutive same-type alerts, unless there was ongoing clinical need for that alert. Outcomes were total number of transmissions and false positives. We performed medical record review to determine if patients experienced any adverse clinical events, including hospitalization and mortality. Among 117 LINQII patients, there were 239 total alerts, 43 (18.0%) of which were false positives. Among 105 LUX-Dx patients, there were 300 total alerts, 115 (38.3%) of which were false positives. LINQIIs were reprogrammed 22 times, resulting in a decrease in median alerts/day from 0.13 to 0.03. LUX-Dx ILRs were reprogrammed 52 times, resulting in a decrease from 0.15 to 0.01 median alerts/day. There were no adverse clinical events that could have been identified by superior or earlier arrhythmia detection. CONCLUSIONS: ILRs with artificial intelligence algorithms and remote reprogramming ability are associated with reduced alert burden because of higher true-positive rates than prior ILRs, without missing potentially consequential arrhythmias.

Hospital Prices for Physician-Administered Drugs for Patients with Private Insurance.

BACKGROUND: Hospitals can leverage their position between the ultimate buyers and sellers of drugs to retain a substantial share of insurer pharmaceutical expenditures. METHODS: In this study, we used 2020-2021 national Blue Cross Blue Shield claims data regarding patients in the United States who had drug-infusion visits for oncologic conditions, inflammatory conditions, or blood-cell deficiency disorders. Markups of the reimbursement prices were measured in terms of amounts paid by Blue Cross Blue Shield plans to hospitals and physician practices relative to the amounts paid by these providers to drug manufacturers. Acquisition-price reductions in hospital payments to drug manufacturers were measured in terms of discounts under the federal 340B Drug Pricing Program. We estimated the percentage of Blue Cross Blue Shield drug spending that was received by drug manufacturers and the percentage retained by provider organizations. RESULTS: The study included 404,443 patients in the United States who had 4,727,189 drug-infusion visits. The median price markup (defined as the ratio of the reimbursement price to the acquisition price) for hospitals eligible for 340B discounts was 3.08 (interquartile range, 1.87 to 6.38). After adjustment for drug, patient, and geographic factors, price markups at hospitals eligible for 340B discounts were 6.59 times (95% confidence interval [CI], 6.02 to 7.16) as high as those in independent physician practices, and price markups at noneligible hospitals were 4.34 times (95% CI, 3.77 to 4.90) as high as those in physician practices. Hospitals eligible for 340B discounts retained 64.3% of insurer drug expenditures, whereas hospitals not eligible for 340B discounts retained 44.8% and independent physician practices retained 19.1%. CONCLUSIONS: This study showed that hospitals imposed large price markups and retained a substantial share of total insurer spending on physician-administered drugs for patients with private insurance. The effects were especially large for hospitals eligible for discounts under the federal 340B Drug Pricing Program on acquisition costs paid to manufacturers. (Funded by Arnold Ventures and the National Institute for Health Care Management.).

Informational Postcards Increase Engagement with Remote Monitoring Among Veterans with Pacemakers and Implantable Cardioverter-Defibrillators: a Stepped-Wedge Randomized Controlled Trial.

BACKGROUND: Remote monitoring (RM) of pacemakers and implantable cardioverter-defibrillators (ICDs) reduces morbidity and mortality. However, many patients are not adherent to RM. OBJECTIVE: To test the effect of informational postcards on RM adherence. DESIGN/PATIENTS: Stepped-wedge randomized controlled trial among Veterans with pacemakers and ICDs. INTERVENTION: In wave 1, Veterans who had sent at least 1 transmission within the past 2 years but had become non-adherent were randomly assigned to receive a postcard or no postcard. Those receiving postcards were randomized to 1 of 2 messages: (1) a"warning" postcard describing risks of non-adherence or (2) an "encouraging" postcard describing benefits of adherence. In wave 2, Veterans who had either not received a postcard in wave 1 or had since become non-adherent were mailed a postcard (again, randomized to 1 of 2 messages). Patients who did not send an RM transmission within 1 month were mailed a second, identical postcard. MAIN MEASURES: Transmission within 70 days. KEY RESULTS: Overall, 6351 Veterans were included. In waves 1 and 2, postcards were mailed to 5657 Veterans (2821 "warning" messages and 2836 "encouraging" messages). Wave 1 included 2178 Veterans as controls (i.e., not mailed a postcard), some of whom received a postcard in wave 2 if they remained non-adherent. In wave 2, 3473 postcards were sent. Of the 5657 patients mailed a postcard, 2756 (48.7%) sent an RM transmission within 70 days, compared to 530 (24.3%) of 2178 controls (absolute difference 24.4%, 95% confidence interval [CI] 22.2%, 26.6%). Of those who sent a transmission, 71.8% did so after the first postcard. Transmission rates at 70 days did not significantly differ between "warning" and "encouraging" messages (odds ratio 1.04, 95% CI 0.92, 1.18). CONCLUSIONS: Informational postcards led to a 24.4% absolute increase in adherence at 70 days among Veterans with pacemakers and ICDs who were non-adherent to RM.

Physicians' Perspectives On FDA Regulation Of Drugs And Medical Devices: A National Survey.

Physicians' knowledge of Food and Drug Administration (FDA) approval processes is important in informing clinical decisions and patient discussions. Among a randomly selected national sample of 509 internists, cardiologists, and oncologists, 41 percent reported moderate or better understanding of the FDA's drug approval process, and 17 percent reported moderate or better understanding of the FDA's medical device approval process. Nearly all physicians thought that randomized, blinded trials that met primary endpoints should be very important factors required to secure regulatory approval. Also, nearly all physicians thought that the FDA should revoke approval for accelerated-approval drugs or breakthrough devices that did not show benefit in postapproval studies. Our findings suggest that physicians commonly lack familiarity with drug and medical device regulatory practices and are under the impression that the data supporting FDA drug and high-risk device approvals are more rigorous than they often are. Physicians would value more rigorous premarket evidence, as well as regulatory action for drugs and devices that do not demonstrate safety and effectiveness in the postmarket setting.

Clinical Phenotyping with an Outcomes-driven Mixture of Experts for Patient Matching and Risk Estimation.

Observational medical data present unique opportunities for analysis of medical outcomes and treatment decision making. However, because these datasets do not contain the strict pairing of randomized control trials, matching techniques are to draw comparisons among patients. A key limitation to such techniques is verification that the variables used to model treatment decision making are also relevant in identifying the risk of major adverse events. This article explores a deep mixture of experts approach to jointly learn how to match patients and model the risk of major adverse events in patients. Although trained with information regarding treatment and outcomes, after training, the proposed model is decomposable into a network that clusters patients into phenotypes from information available before treatment. This model is validated on a dataset of patients with acute myocardial infarction complicated by cardiogenic shock. The mixture of experts approach can predict the outcome of mortality with an area under the receiver operating characteristic curve of 0.85 ± 0.01 while jointly discovering five potential phenotypes of interest. The technique and interpretation allow for identifying clinically relevant phenotypes that may be used both for outcomes modeling as well as potentially evaluating individualized treatment effects.

Barriers and Facilitators Associated With Remote Monitoring Adherence Among Veterans With Pacemakers and Implantable Cardioverter-Defibrillators: Qualitative Cross-Sectional Study.

BACKGROUND: The Heart Rhythm Society strongly recommends remote monitoring (RM) of cardiovascular implantable electronic devices (CIEDs) because of the clinical outcome benefits to patients. However, many patients do not adhere to RM and, thus, do not achieve these benefits. There has been limited study of patient-level barriers and facilitators to RM adherence; understanding patient perspectives is essential to developing solutions to improve adherence. OBJECTIVE: We sought to identify barriers and facilitators associated with adherence to RM among veterans with CIEDs followed by the Veterans Health Administration. METHODS: We interviewed 40 veterans with CIEDs regarding their experiences with RM. Veterans were stratified into 3 groups based on their adherence to scheduled RM transmissions over the past 2 years: 6 fully adherent (≥95%), 25 partially adherent (≥65% but <95%), and 9 nonadherent (<65%). As the focus was to understand challenges with RM adherence, partially adherent and nonadherent veterans were preferentially weighted for selection. Veterans were mailed a letter stating they would be called to understand their experiences and perspectives of RM and possible barriers, and then contacted beginning 1 week after the letter was mailed. Interviews were structured (some questions allowing for open-ended responses to dive deeper into themes) and focused on 4 predetermined domains: knowledge of RM, satisfaction with RM, reasons for nonadherence, and preferences for health care engagement. RESULTS: Of the 44 veterans contacted, 40 (91%) agreed to participate. The mean veteran age was 75.3 (SD 7.6) years, and 98% (39/40) were men. Veterans had been implanted with their current CIED for an average of 4.4 (SD 2.8) years. A total of 58% (23/40) of veterans recalled a discussion of home monitoring, and 45% (18/40) reported a good understanding of RM; however, when asked to describe RM, their understanding was sometimes incomplete or not correct. Among the 31 fully or partially adherent veterans, nearly all were satisfied with RM. Approximately one-third recalled ever being told the results of a remote transmission. Among partially or nonadherent veterans, only one-fourth reported being contacted by a Department of Veterans Affairs health care professional regarding not having sent a remote transmission; among those who had troubleshooted to ensure they could send remote transmissions, they often relied on the CIED manufacturer for help (this experience was nearly always positive). Most nonadherent veterans felt more comfortable engaging in RM if they received more information or education. Most veterans were interested in being notified of a successful remote transmission and learning the results of their remote transmissions. CONCLUSIONS: Veterans with CIEDs often had limited knowledge about RM and did not recall being contacted about nonadherence. When they were contacted and troubleshooted, the experience was positive. These findings provide opportunities to optimize strategies for educating and engaging patients in RM.

Studies Of Prescription Digital Therapeutics Often Lack Rigor And Inclusivity.

Little is known about the evidence to support prescription digital therapeutics, which are digital tools that rely primarily on software for diagnosis or treatment that have indications for use regulated by the Food and Drug Administration (FDA) and require a clinician's prescription. We conducted the first retrospective cross-sectional analysis of clinical studies of twenty prescription digital therapeutics authorized by the FDA and available on the market as of November 2022. Our analysis found that just two prescription digital therapeutics had been evaluated in at least one study that was randomized and blinded and that used other rigorous standards of evidence. Two-thirds of clinical studies of prescription digital therapeutics were conducted on a postmarket basis, with less rigorous standards of evidence than the standards used in premarket studies. More than half of studies did not report data on participants' race, and more than 80 percent did not report their ethnicity. More than one-third required English proficiency, and nearly half of nonpediatric studies had an upper age limit. These results suggest the need for a more rigorous and inclusive approach to clinical research supporting FDA-authorized prescription digital therapeutics. A stronger evidence base would increase confidence in these technologies' effectiveness and would enable more informed decision making about their clinical use and coverage.

Cardiac coronary tomography angiography (CCTA) use across geographical regions in the USA and the UK: a cross-sectional study.

Objective: Increased use of CT imaging has been identified as a key component of unsustainable rising healthcare costs in the USA and globally. Understanding evidence and its relation to imaging coverage policies can help identify patterns of variation to better inform high value care initiatives. This cross-sectional study evaluates regional differences in US utilisation of cardiac coronary tomography angiography (CCTA) and compares use in the USA and England. Design: We determined differences in CCTA order rates by US Medicare region and compared order rates in the US and England, compared CT scanner prevalence in the USA and UK, and reviewed the CCTA coverage policies for each region. Setting: The US and the UK. Participants: Medicare Coverage Database; Medicare 2018 Part B data; National Health Services 2018 data. Interventions: CCTA orders, CT scanner prevalence. Main outcome measures: CCTA orders per beneficiary, CT scanner prevalence, CCTA policy variation. Results: We found that CCTA coverage policies are more permissive in the UK compared with the USA. However, CT scanner prevalence per beneficiary is four times greater in the USA than the UK. There was significant variation in number of CCTA ordered per 100 000 beneficiaries between regions in England and the USA, ranging from 74 to 313 in the US and 57-317 in England. Conclusions: There is significant geographical variation in use of CCTA in both the USA and England, although overall use does not differ significantly between both countries. Similarities in order rates, despite a much higher CT scanner density in the USA, may be related to more permissive guidelines around use of CCTA in the UK. Variation in both countries may also reflect the lack of high-quality clinical outcomes data for use of CCTA, underscoring opportunities for more evidence and evidence-based policy to promote appropriate use of CCTA imaging.

Deep Learning of Electrocardiograms in Sinus Rhythm From US Veterans to Predict Atrial Fibrillation.

Importance: Early detection of atrial fibrillation (AF) may help prevent adverse cardiovascular events such as stroke. Deep learning applied to electrocardiograms (ECGs) has been successfully used for early identification of several cardiovascular diseases. Objective: To determine whether deep learning models applied to outpatient ECGs in sinus rhythm can predict AF in a large and diverse patient population. Design, Setting, and Participants: This prognostic study was performed on ECGs acquired from January 1, 1987, to December 31, 2022, at 6 US Veterans Affairs (VA) hospital networks and 1 large non-VA academic medical center. Participants included all outpatients with 12-lead ECGs in sinus rhythm. Main Outcomes and Measures: A convolutional neural network using 12-lead ECGs from 2 US VA hospital networks was trained to predict the presence of AF within 31 days of sinus rhythm ECGs. The model was tested on ECGs held out from training at the 2 VA networks as well as 4 additional VA networks and 1 large non-VA academic medical center. Results: A total of 907 858 ECGs from patients across 6 VA sites were included in the analysis. These patients had a mean (SD) age of 62.4 (13.5) years, 6.4% were female, and 93.6% were male, with a mean (SD) CHA2DS2-VASc (congestive heart failure, hypertension, age, diabetes mellitus, prior stroke or transient ischemic attack or thromboembolism, vascular disease, age, sex category) score of 1.9 (1.6). A total of 0.2% were American Indian or Alaska Native, 2.7% were Asian, 10.7% were Black, 4.6% were Latinx, 0.7% were Native Hawaiian or Other Pacific Islander, 62.4% were White, 0.4% were of other race or ethnicity (which is not broken down into subcategories in the VA data set), and 18.4% were of unknown race or ethnicity. At the non-VA academic medical center (72 483 ECGs), the mean (SD) age was 59.5 (15.4) years and 52.5% were female, with a mean (SD) CHA2DS2-VASc score of 1.6 (1.4). A total of 0.1% were American Indian or Alaska Native, 7.9% were Asian, 9.4% were Black, 2.9% were Latinx, 0.03% were Native Hawaiian or Other Pacific Islander, 74.8% were White, 0.1% were of other race or ethnicity, and 4.7% were of unknown race or ethnicity. A deep learning model predicted the presence of AF within 31 days of a sinus rhythm ECG on held-out test ECGs at VA sites with an area under the receiver operating characteristic curve (AUROC) of 0.86 (95% CI, 0.85-0.86), accuracy of 0.78 (95% CI, 0.77-0.78), and F1 score of 0.30 (95% CI, 0.30-0.31). At the non-VA site, AUROC was 0.93 (95% CI, 0.93-0.94); accuracy, 0.87 (95% CI, 0.86-0.88); and F1 score, 0.46 (95% CI, 0.44-0.48). The model was well calibrated, with a Brier score of 0.02 across all sites. Among individuals deemed high risk by deep learning, the number needed to screen to detect a positive case of AF was 2.47 individuals for a testing sensitivity of 25% and 11.48 for 75%. Model performance was similar in patients who were Black, female, or younger than 65 years or who had CHA2DS2-VASc scores of 2 or greater. Conclusions and Relevance: Deep learning of outpatient sinus rhythm ECGs predicted AF within 31 days in populations with diverse demographics and comorbidities. Similar models could be used in future AF screening efforts to reduce adverse complications associated with this disease.

Aligning US Agency Policies for Cardiovascular Devices Through the Breakthrough Devices Program.

Importance: The US Food and Drug Administration (FDA) and Centers for Medicare & Medicaid Services (CMS) have different statutory authorities; FDA evaluates safety and effectiveness for market authorization of medical devices while CMS determines whether coverage is "reasonable and necessary" for its beneficiaries. CMS has recently enacted policies automatically providing supplemental reimbursement for new, costly devices authorized after designation in FDA's Breakthrough Devices Program (BDP) and in June 2023 issued notice for a new Transitional Coverage for Emerging Technologies pathway, accelerating coverage for Breakthrough devices. Observations: Aiming to incentivize innovation, FDA awards Breakthrough designations early in device development to expedite market authorization and can accept greater uncertainty in benefit and risk, contingent on postmarket evidence generation. Since 2020, Breakthrough designation has effectively automatically qualified devices to receive supplemental Medicare reimbursement after CMS waived a long-standing requirement that devices demonstrate "substantial clinical improvement" for beneficiaries. Using publicly available information, 3 examples of cardiovascular devices illustrate that the BDP may allow for FDA authorization based on less rigorous evidence, such as single-arm trials focused on surrogate end points with short-term follow-up whose participants are often not representative of Medicare beneficiaries. In 1 case, Breakthrough designation allowed a 30% decrease in enrollment of a trial used to support approval. Initial positive findings for some devices have remained unverified, and in 1 case even partially nullified, by postmarket studies. Manufacturers have also used Breakthrough designations to set the price of devices to facilitate additional pass-through payments, leading to higher short-term and long-term costs to CMS and health care systems. Conclusions and Relevance: The BDP may qualify new, costly devices for higher and automatic Medicare reimbursement despite evidence not being representative of CMS beneficiaries and persistent uncertainty of benefit and risk. To ensure the best evidence is generated to inform clinical care, FDA could apply more selectivity to BDP eligibility, specify objective criteria for revoking Breakthrough designation when appropriate, and ensure timely postmarket evidence generation, whereas CMS could independently review clinical evidence, advise manufacturers about standards for coverage review, and make supplemental payments and long-term device reimbursement contingent on clinical outcome benefit and postmarket evidence generation.

A Critical Examination of Independent Medical Review Decision-making for Cardiovascular Procedures Shows Low Rate of Evidence Citation in Reviews.

BACKGROUND: The California Independent Medical Review (IMR) program was created in 2001 to provide an independent, external evaluation of insurers' denials of coverage of health services. OBJECTIVE: We sought to evaluate the quality and comprehensiveness of data used to support IMR decision-making between 2015 and 2020. RESULTS: Of the 159 cases submitted to IMR regarding denials of cardiovascular procedures, 52% of these denials were overturned by IMR, thus restoring coverage. Despite a state-wide requirement that specific references to medical and scientific evidence should be provided in IMR reviews, fewer than a quarter of reviews cited any evidence to support decision-making. Slightly more than one third of IMR review decisions were inconsistent with recommendations from professional societies and peer-reviewed evidence; the primary reason for these inconsistencies was that invasive interventions were often recommended by reviewers before utilizing guideline-directed medical or less invasive therapies. CONCLUSION: Our findings highlight an opportunity for improvement in the quality of IMR decision-making through a more consistent use of available scientific evidence to guide clinical reasoning.

Assessing the use of observational methods and real-world data to emulate ongoing randomized controlled trials.

BACKGROUND/AIMS: There has been growing interest in better understanding the potential of observational research methods in medical product evaluation and regulatory decision-making. Previously, we used linked claims and electronic health record data to emulate two ongoing randomized controlled trials, characterizing the populations and results of each randomized controlled trial prior to publication of its results. Here, our objective was to compare the populations and results from the emulated trials with those of the now-published randomized controlled trials. METHODS: This study compared participants' demographic and clinical characteristics and study results between the emulated trials, which used structured data from OptumLabs Data Warehouse, and the published PRONOUNCE and GRADE trials. First, we examined the feasibility of implementing the baseline participant characteristics included in the published PRONOUNCE and GRADE trials' using real-world data and classified each variable as ascertainable, partially ascertainable, or not ascertainable. Second, we compared the emulated trials and published randomized controlled trials for baseline patient characteristics (concordance determined using standardized mean differences <0.20) and results of the primary and secondary endpoints (concordance determined by direction of effect estimates and statistical significance). RESULTS: The PRONOUNCE trial enrolled 544 participants, and the emulated trial included 2226 propensity score-matched participants. In the PRONOUNCE trial publication, one of the 32 baseline participant characteristics was listed as an exclusion criterion on ClinicalTrials.gov but was ultimately not used. Among the remaining 31 characteristics, 9 (29.0%) were ascertainable, 11 (35.5%) were partially ascertainable, and 10 (32.2%) were not ascertainable using structured data from OptumLabs. For one additional variable, the PRONOUNCE trial did not provide sufficient detail to allow its ascertainment. Of the nine variables that were ascertainable, values in the emulated trial and published randomized controlled trial were discordant for 6 (66.7%). The primary endpoint of time from randomization to the first major adverse cardiovascular event and secondary endpoints of nonfatal myocardial infarction and stroke were concordant between the emulated trial and published randomized controlled trial. The GRADE trial enrolled 5047 participants, and the emulated trial included 7540 participants. In the GRADE trial publication, 8 of 34 (23.5%) baseline participant characteristics were ascertainable, 14 (41.2%) were partially ascertainable, and 11 (32.4%) were not ascertainable using structured data from OptumLabs. For one variable, the GRADE trial did not provide sufficient detail to allow for ascertainment. Of the eight variables that were ascertainable, values in the emulated trial and published randomized controlled trial were discordant for 4 (50.0%). The primary endpoint of time to hemoglobin A1c ≥7.0% was mostly concordant between the emulated trial and the published randomized controlled trial. CONCLUSION: Despite challenges, observational methods and real-world data can be leveraged in certain important situations for a more timely evaluation of drug effectiveness and safety in more diverse and representative patient populations.