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.

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.

Physician Perspectives on the Food and Drug Administration's Decision to Grant Accelerated Approval to Aducanumab for Alzheimer's Disease.

In June 2021, the US Food and Drug Administration (FDA) granted accelerated approval to aducanumab, a monoclonal antibody indicated for the treatment of Alzheimer's disease. The accelerated approval decision was controversial due to concerns about the use of an unvalidated surrogate measure, beta-amyloid, as the basis for approval and a lack of clinical outcome benefit. Between October 2021 and September 2022, we conducted a survey of a nationally representative group of internists, medical oncologists, and cardiologists to understand perspectives around aducanumab's approval and how this FDA decision may influence trust in other drugs approved through the accelerated approval program. Among 214 physician respondents familiar with the accelerated approval of aducanumab, 184 (86%) would not prescribe or recommend aducanumab. Further, 143 (67%) physicians reported losing trust in other drugs approved through the accelerated approval program due to the FDA's decision with aducanumab. As a growing number of similar novel Alzheimer's disease treatments are on the horizon, the first of which, lecanemab, already has received accelerated approval in January 2023, our survey findings provide insight into the impact of the FDA's regulatory decisions on the perspectives and prescribing behavior of physicians concerning these novel drug treatments.

Long-term Outcomes in Use of Opioids, Nonpharmacologic Pain Interventions, and Total Costs of Spinal Cord Stimulators Compared With Conventional Medical Therapy for Chronic Pain.

Importance: Spinal cord stimulators (SCSs) are increasingly used for the treatment of chronic pain. There is a need for studies with long-term follow-up. Objective: To determine the comparative effectiveness and costs of SCSs compared with conventional medical management (CMM) in a large cohort of patients with chronic pain. Design, Setting, and Participants: This was a 1:5 propensity-matched retrospective comparative effectiveness research analysis of insured individuals from April 1, 2016, to August 31, 2018. This study used administrative claims data, including longitudinal medical and pharmacy claims, from US commercial and Medicare Advantage enrollees 18 years or older in Optum Labs Data Warehouse. Patients with incident diagnosis codes for failed back surgery syndrome, complex regional pain syndrome, chronic pain syndrome, and other chronic postsurgical back and extremity pain were included in this study. Data were analyzed from February 1, 2021, to August 31, 2022. Exposures: SCSs or CMM. Main Outcomes and Measures: Surrogate measures for primary chronic pain treatment modalities, including pharmacologic and nonpharmacologic pain interventions (epidural and facet corticosteroid injections, radiofrequency ablation, and spine surgery), as well as total costs. Results: In the propensity-matched population of 7560 patients, mean (SD) age was 63.5 (12.5) years, 3080 (40.7%) were male, and 4480 (59.3%) were female. Among matched patients, during the first 12 months, patients treated with SCSs had higher odds of chronic opioid use (adjusted odds ratio [aOR], 1.14; 95% CI, 1.01-1.29) compared with patients treated with CMM but lower odds of epidural and facet corticosteroid injections (aOR, 0.44; 95% CI, 0.39-0.51), radiofrequency ablation (aOR, 0.57; 95% CI, 0.44-0.72), and spine surgery (aOR, 0.72; 95% CI, 0.61-0.85). During months 13 to 24, there was no significant difference in chronic opioid use (aOR, 1.06; 95% CI, 0.94-1.20), epidural and facet corticosteroid injections (aOR, 1.00; 95% CI, 0.87-1.14), radiofrequency ablation (aOR, 0.84; 95% CI, 0.66-1.09), or spine surgery (aOR, 0.91; 95% CI, 0.75-1.09) with SCS use compared with CMM. Overall, 226 of 1260 patients (17.9%) treated with SCS experienced SCS-related complications within 2 years, and 279 of 1260 patients (22.1%) had device revisions and/or removals, which were not always for complications. Total costs of care in the first year were $39 000 higher with SCS than CMM and similar between SCS and CMM in the second year. Conclusions and Relevance: In this large, real-world, comparative effectiveness research study comparing SCS and CMM for chronic pain, SCS placement was not associated with a reduction in opioid use or nonpharmacologic pain interventions at 2 years. SCS was associated with higher costs, and SCS-related complications were common.

Elastin Degradation and Lung Function Deterioration with Remote Secondhand Tobacco Smoke Exposure in Never-smokers.

Background: Prolonged past exposure to secondhand tobacco smoke (SHS) in never-smokers is associated with abnormal lung function and reduced diffusing capacity suggestive of an associated lung tissue injury and damage. The mechanisms by which past SHS exposure may contribute to lung tissue damage are unknown. Elastin is a major constituent of extracellular matrix in lung parenchyma. Objective: To determine whether past exposure to SHS is associated with ongoing lung tissue damage as indicated by elevated elastin degradation products that are linked to lung function. Methods: We measured the plasma levels of elastin degradation markers (EDM) from 193 never-smoking flight attendants with a history of remote SHS exposure in aircraft cabins and 103 nonsmoking flight attendants or sea-level control participants without such history of cabin SHS exposure and examined those levels versus their lung function with adjustment for covariates. The cabin SHS exposure was estimated based on airline employment history and years of the smoking ban enactment. Results: The median [interquartile range] plasma EDM level for all participants was 0.30 [0.24-0.36] ng/mL with a total range of 0.16-0.65 ng/mL. Plasma EDM levels were elevated in those with a history of exposure to cabin SHS compared to those not exposed (0.33±0.08 versus 0.26±0.06 ng/mL; age- and sex-adjusted P<0.001). In those with a history of cabin SHS exposure, higher EDM levels were associated with a lower diffusing capacity (parameter estimate [PE] 95% [confidence interval(CI)]=4.2 [0.4-8.0] %predicted decrease per 0.1 ng/mL increase in EDM; P=0.030). Furthermore, EDM levels were inversely associated with forced expiratory volume in 1 second (FEV1), FEV1 to forced vital capacity (FVC) ratio , and forced expiratory flow rate between 25% and 75% ( FEF25%-75%) (PE [95%CI]=5.8 [2.1-9.4], 4.0 [2.2-5.7], and 12.5 [5.8-19.2] %predicted decrease per 0.1 ng/mL increase in EDM, respectively; P<0.001). Plasma EDM mediated a substantial fraction of the association of SHS with FEV1, FVC, and FEF25%-75% (P<0.05). Conclusions: Long after past exposure to SHS, there is ongoing elastin degradation beyond what is expected from the aging process, which likely contributes to lower lung function and a reduced pulmonary capillary bed as seen in chronic obstructive pulmonary disease (COPD).

Single vs Serial Measurements of Cardiac Troponin Level in the Evaluation of Patients in the Emergency Department With Suspected Acute Myocardial Infarction.

Importance: Chest pain is among the most common reasons for emergency department (ED) presentations. However, most patients are at low risk for acute coronary syndrome (ACS), with low cardiac adverse outcomes rates. Biomarker testing with troponin levels is key in the initial assessment for ACS. Although serial troponin testing can improve the diagnosis of ACS in clinical practice, some patients deemed to be low risk are discharged after a single negative troponin test result. Objective: To report the clinical outcomes of patients discharged after a single negative troponin test result compared with patients discharged after serial troponin measurements. Design, Setting, and Participants: This is a retrospective cohort study of ED encounters from May 5, 2016, to December 1, 2017, across 15 community EDs within an integrated health care system in southern California. The study cohort includes 27 918 adult ED encounters in which patients were evaluated for suspected ACS with a HEART (history, electrocardiogram, age, risk factors, and troponin) score and an initial conventional troponin-I measurement below the level of detection (<0.02 ng/mL). Statistical analysis was performed from December 1, 2019, to December 1, 2020. Exposure: Single troponin test vs multiple troponin tests. Main Outcomes and Measures: The primary outcome was acute myocardial infarction or cardiac mortality; secondary outcomes included coronary artery bypass graft, percutaneous coronary intervention, invasive coronary angiography, and unstable angina within 30 days of discharge. A multivariable logistic regression model was performed to evaluate the association between testing strategies and clinical outcomes. Results: A total of 27 918 patient encounters (16 212 women [58.1%]; mean [SD] age, 58.7 [15.2] years) were included in the study. Of patients with an initial troponin measurement below the level of detection, 14 459 (51.8%) were discharged after a single troponin measurement, and 13 459 (48.2%) underwent serial troponin tests. After adjustment for cardiac risk factors and comorbidities, there was no statistically significant difference in the primary outcome of acute myocardial infarction or cardiac mortality within 30 days between the 2 groups (single troponin, 56 [0.4%] vs serial troponin, 52 [0.4%]; adjusted odds ratio, 1.41 [95% CI, 0.96-2.07]). Patients discharged after a single troponin test had lower rates of coronary artery bypass graft (adjusted odds ratio, 0.24 [95% CI, 0.11-0.48]) and invasive coronary angiography (adjusted odds ratio, 0.46 [95% CI, 0.38-0.56]). Conclusions and Relevance: This study suggests that patients are routinely discharged from the ED after a single negative troponin test result, and when compared with serial troponin testing, a single troponin test appears safe based on current physician decision-making, with no difference in rates of 30-day cardiac mortality and acute myocardial infarction, which are low in both groups.

Vascular Aging Is Accelerated in Flight Attendants With Occupational Secondhand Smoke Exposure.

OBJECTIVE: To determine whether early vascular aging may be present in flight attendants with remote in-cabin secondhand smoke (SHS) exposure. METHODS: Twenty-six flight attendants with a history of in-cabin SHS exposure prior to the airline smoking bans were recruited. Pulse wave analysis, peripheral arterial tonometry, and brachial artery reactivity testing evaluated their arterial compliance and endothelial function. RESULTS: Flight attendants with remote in-cabin SHS exposure have normal blood pressure, pulse wave velocity, and reactive hyperemia index, but abnormal pulse pressure, augmentation index, flow-mediated dilation, and hyperemic mean flow ratio. CONCLUSION: These preliminary findings suggest that flight attendants with remote in-cabin SHS exposure have preclinical signs of accelerated vascular aging and raise new questions about the relationship between remote SHS exposure and vascular health.