Impact of Study Hypotheses on Results From Randomized Clinical Trials: Comparison Between Standard and Noninferiority Randomized Clinical Trials

Background: In embarking on randomized clinical trials (RCTs), researchers can hypothesize that a more intensive treatment is better than a less intensive treatment (positive hypothesis) or that a less intensive treatment is similar or noninferior to a more intensive treatment (negative hypothesis). Researchers may design noninferiority RCTs (NI-RCTs) to support negative hypotheses and standard RCTs (S-RCTs) to support negative or positive hypotheses. Regardless of hypotheses, S-RCTs and NI-RCTs should produce consistent results when assessing similar participants, interventions, control, and outcomes. Objective: To compare effect estimates in S-RCTs with positive hypotheses versus NI-RCTs and in S-RCTs with negative hypotheses versus NI-RCTs. Design: Meta-research. Setting: 98 meta-analyses. Participants: 468 RCTs, including 153 NI-RCTs and 315 S-RCTs (149 positive and 166 negative hypotheses). Intervention: S-RCTs as the exposure and NI-RCTs as the control. Measurements: The ratio of effect estimates between S-RCTs and NI-RCTs in each meta-analysis was combined across meta-analyses. Results: Standard RCTs with positive hypotheses produced effect estimates 1.47 (95% CI, 1.27 to 1.70) times larger than NI-RCTs; among RCTs rated as having low risk of bias for blinding, the ratio was 1.01 (CI, 0.70 to 1.45), whereas among those rated as having high or unclear risk of bias for blinding, the ratio was 1.81 (CI, 1.41 to 2.33). Standard RCTs with negative hypotheses did not produce statistically different effect estimates from NI-RCTs (ratio, 0.93 [CI, 0.84 to 1.03]). Limitation: Findings may be limited by residual differences between S-RCTs and NI-RCTs in the same meta-analysis. Conclusion: The researchers’ hypotheses may bias the results of published RCTs, especially those with high or unclear risk of bias for blinding. The effect of researchers’ hypotheses should be assessed in systematic reviews and clinical practice guidelines when RCTs addressing the same clinical question report conflicting hypotheses. Primary Funding Source: The Shenzhen Municipal Government, Guangdong Province, China, and the Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences.

Quality Indicators for Screening and Surveillance of Colorectal Cancer in Adults: A Review of Performance Measures by the American College of Physicians

Colorectal cancer is the second leading cause of cancer-related deaths for both men and women. Screening for colorectal cancer is an effective strategy to reduce morbidity and mortality, but uptake remains suboptimal. Several performance measures for colorectal cancer screening and surveillance are currently used in pay-for-performance, public reporting, and/or accountability programs. The American College of Physicians (ACP) embraces performance measurement as a means to improve quality of care. The ACP believes that a performance measure must be methodologically sound and evidence-based to be considered for inclusion in payment, accountability, or reporting programs. These principles are critical given the potential effect to physician administrative work and reputation and reimbursement and to prevent unintended consequences on patient care. The ACP’s Performance Measurement Committee (PMC) reviews performance measures using a validated process to recognize high-quality performance measures, address gaps and areas for improvement in performance measures, and help reduce reporting burden. This article aims to present a review of current performance measures for colorectal cancer screening and surveillance to inform physicians, payers, and policymakers in their selection and use of performance measures and make recommendations for measures that could be developed. The PMC appreciates the importance of colorectal cancer screening in the prevention and early detection of colorectal cancer and supports performance measures based on strong recommendations. The PMC reviewed 5 performance measures for colorectal cancer screening relevant to internal medicine and supports 1 performance measure (“Facility 7-Day Risk-Standardized Hospital Visit Rate after Outpatient Colonoscopy”) for use.

Annals On Call - Metabolic Dysfunction–Associated Steatotic Liver Disease

Unifying Efforts to Empower Equitable Obesity Care: Synopsis of an American College of Physicians and Council of Subspecialty Societies Summit

Obesity is a leading cause of morbidity and mortality with health consequences that crosscut most medical specialties. Despite the emergence of effective and promising new therapies, many impediments to comprehensive obesity care remain. As part of their commitment to improving obesity care, the American College of Physicians (ACP) and its Council of Subspecialty Societies (CSS) held a summit on 24 October 2023 to identify barriers to and opportunities for collaborative action in the domains of physician education, health care policy and care delivery, and addressing weight bias. This report summarizes the summit proceedings and provides a postsummit synthesis from ACP and CSS. Key themes were centered on knowledge, advocacy, action, and compassion, including the need for culture change, paradigm shifts, and stakeholder engagement and collaboration; a focus on empowerment of both clinicians and patients; the importance of knowing patients as people to help address social determinants of health; the need to address learned helplessness; and the importance of embracing artificial intelligence and technology as disruptive innovations. Recommendations for next steps for collaborative action include leveraging and improving already available educational and clinical resources, developing obesity education and care standards that incorporate patients’ perspectives and address social determinants of health, developing community and public–private partnerships to improve access and public awareness, and coordinating messaging and policy advocacy efforts that align with mitigating the longstanding obesity epidemic.

Extracorporeal Shock-Wave Lithotripsy and Endoscopy for the Treatment of Pain in Chronic Pancreatitis

Extracorporeal Shock-Wave Lithotripsy and Endoscopy for the Treatment of Pain in Chronic Pancreatitis

Associations of Testosterone and Related Hormones With All-Cause and Cardiovascular Mortality and Incident Cardiovascular Disease in Men

Medications and Risk for Microscopic Colitis: A Nationwide Study of Older Adults in Sweden

Background: Several medications have been identified as potential risk factors for microscopic colitis (MC), but evidence so far is hampered by methodological limitations. Objective: To examine the potential causal effects of previously implicated medications on risk for MC. Design: Emulation of 6 target trials. Setting: Sweden. Participants: All residents in Sweden aged 65 years or older between 2006 and 2017 who met eligibility criteria (n = 191 482 to 2 634 777). Measurements: The primary outcome was biopsy-verified MC. The date of diagnosis was obtained from the nationwide histopathology cohort ESPRESSO (Epidemiology Strengthened by histoPathology Reports in Sweden). Twelve- and 24-month cumulative incidences and absolute risk differences for MC were estimated via inverse probability weighing. Results: The 12- and 24-month cumulative incidences of MC were less than 0.5% under all treatment strategies. Estimated 12-month risk differences were close to null under angiotensin-converting enzyme versus calcium-channel blocker (CCB) initiation, angiotensin-receptor blocker versus CCB initiation, nonsteroidal anti-inflammatory drug initiation versus noninitiation, proton-pump inhibitor initiation versus noninitiation, and statin initiation versus noninitiation. The estimated 12-month risk difference was 0.04% (95% CI, 0.03% to 0.05%) for selective serotonin receptor inhibitors (SSRIs) versus mirtazapine. Results were similar for 24-month risk differences. Several medications were also associated with increased risk for receiving a colonoscopy with a normal colorectal mucosa biopsy result. Limitations: There is possible residual bias due to differential health care utilization or surveillance. Lack of primary care data limited measurement of, and adjustment for, symptoms and medical diagnoses that increase risk for receiving a colonoscopy. Conclusion: No evidence of a causal relationship between most previously suspected pharmacologic triggers and risk for MC was found. Previously reported associations and persistent associations with SSRI initiation may be due to surveillance bias. Primary Funding Source: The National Institutes of Health and the Swedish Research Council.

Antibiotic, Glucocorticoid, and Opioid Prescribing in Urgent Cares: An Opportunity for Reducing Medication Overuse

Annals for Educators - December 2024