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Key Points Question How does the public view emergency research conducted with an exception from informed consent (EFIC)? Findings In this systematic review of survey data from 27 emergency clinical trials with responses from 42 448 individuals submitted by EFIC trial organizers to the US Food and Drug Administration, public attitudes regarding EFIC varied: 58.4% approved of EFIC in principle, 68.6% approved of family-member enrollment, 73.0% approved of personal enrollment, and 86.5% approved of community inclusion. Groups surveyed with higher proportions of African American and male respondents had lower rates of EFIC approval, and these groups were underrepresented in surveys relative to their enrollment in EFIC trials. Meaning The US Food and Drug Administration should aim to build greater public consensus around the appropriate use of EFIC., This systematic review analyzes data from surveys conducted as part of community consultation to assess levels of public approval of trials conducted with an exception from informed consent., Importance The US Food and Drug Administration (FDA) created the exception from informed consent (EFIC) pathway in 1996 to allow some emergency trials to enroll patients without informed consent. To protect individual autonomy and preserve public trust, the FDA requires that EFIC trial investigators consult with community members before a trial may begin. Objectives To analyze data from surveys conducted as part of community consultation ahead of EFIC trials and assess levels of public approval. Data Sources All trials granted an EFIC must submit documentation of compliance with EFIC regulations to a publicly available docket at the FDA. Submissions between November 1, 1996, and October 23, 2017, were reviewed. Study Selection Trials with survey data were included. Data Extraction and Synthesis Data were extracted between January 2018 and June 2018 and were analyzed between June 2018 and August 2018. The quality and validity of data were assessed according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. A random-effects metaregression was used to assess the association of demographic characteristics with EFIC approval. Main Outcomes and Measures The primary study outcome was EFIC approval. Results The FDA docket contained 15 958 pages of material with survey data for 42 448 individuals submitted by 27 trials. Public approval of EFIC varied by question type, with more people willing to approve initiation of EFIC trials in their community (86.5%) than personal enrollment (73.0%), enrollment of a family member (68.6%), or the principle of enrollment without consent (58.4%) (P

Importance Osteoporosis medication treatment is recommended after hip fracture, yet contemporary estimates of rates of initiation and clinical benefit in the patient population receiving routine care are not well documented. Objectives To report osteoporosis treatment initiation rates between January 1, 2004, and September 30, 2015, and to estimate the risk reduction in subsequent nonvertebral fractures associated with treatment initiation in patients with hip fracture. Design, Setting, and Participants In this cohort study, data from a commercial insurance claims database from the United States were analyzed. Patients 50 years and older who had a hip fracture and were not receiving treatment with osteoporosis medications before their fracture were included. Exposure Prescription dispensing of an osteoporosis medication within 180 days of a hip fracture hospitalization. Main Outcomes and Measures Each initiation episode was matched with 10 nonuse episodes on person-time after the index hip fracture event to preclude immortal time bias and followed up for the outcome of nonvertebral fracture until change in exposure or a censoring event. An instrumental variable analysis using 2-stage residual inclusion method was conducted using calendar year, specialist access, geographical variation in prescribing patterns, and hospital preference. Results Among 97 169 patients with a hip fracture identified, the mean (SD) age was 80.2 (10.8) years, and 64 164 (66.0%) were women. A continuous decline over the study years was observed in osteoporosis medication initiation rates from 9.8% (95% CI, 9.0%-10.6%) in 2004 to 3.3% (95% CI, 2.9%-3.8%) in 2015. In the effectiveness analyses, the hospital preference instrumental variable had a stronger association with treatment (pseudoR2 = 0.20) than the other 3 instrumental variables (specialist access: pseudoR2 = 0.04; calendar year: pseudoR2 = 0.05; and geographic variation: pseudoR2 = 0.07). Instrumental variable analysis with hospital preference suggested a rate difference of 4.2 events (95% CI, 1.1-7.3) per 100 person-years in subsequent fractures associated with osteoporosis treatment initiation compared with nonuse in an additive hazard model. Conclusions and Relevance Low rates of osteoporosis treatment initiation after a hip fracture in recent years were observed. Clinically meaningful reduction in subsequent nonvertebral fracture rates associated with treatment suggests that improving prescriber adherence to guidelines and patient adherence to prescribed regimens may result in notable public health benefit.

Importance Many investigational drugs fail in late-stage clinical development. A better understanding of why investigational drugs fail can inform clinical practice, regulatory decisions, and future research. Objective To assess factors associated with regulatory approval or reasons for failure of investigational therapeutics in phase 3 or pivotal trials and rates of publication of trial results. Design, Setting, and Participants Using public sources and commercial databases, we identified investigational therapeutics that entered pivotal trials between 1998 and 2008, with follow-up through 2015. Agents were classified by therapeutic area, orphan designation status, fast track designation, novelty of biological pathway, company size, and as a pharmacologic or biologic product. Main Outcomes and Measures For each product, we identified reasons for failure (efficacy, safety, commercial) and assessed the rates of publication of trial results. We used multivariable logistic regression models to evaluate factors associated with regulatory approval. Results Among 640 novel therapeutics, 344 (54%) failed in clinical development, 230 (36%) were approved by the US Food and Drug Administration (FDA), and 66 (10%) were approved in other countries but not by the FDA. Most products failed due to inadequate efficacy (n = 195; 57%), while 59 (17%) failed because of safety concerns and 74 (22%) failed due to commercial reasons. The pivotal trial results were published in peer-reviewed journals for 138 of the 344 (40%) failed agents. Of 74 trials for agents that failed for commercial reasons, only 6 (8.1%) were published. In analyses adjusted for therapeutic area, agent type, firm size, orphan designation, fast-track status, trial year, and novelty of biological pathway, orphan-designated drugs were significantly more likely than nonorphan drugs to be approved (46% vs 34%; adjusted odds ratio [aOR], 2.3; 95% CI, 1.4-3.7). Cancer drugs (27% vs 39%; aOR, 0.5; 95% CI, 0.3-0.9) and agents sponsored by small and medium-size companies (28% vs 42%; aOR, 0.4; 95% CI, 0.3-0.7) were significantly less likely to be approved. Conclusions and Relevance Roughly half of investigational drugs entering late-stage clinical development fail during or after pivotal clinical trials, primarily because of concerns about safety, efficacy, or both. Results for the majority of studies of investigational drugs that fail are not published in peer-reviewed journals.

Importance Pharmaceutical industry payments to physicians may affect prescribing practices and increase costs if more expensive medications are prescribed. Objective Determine the association between industry payments to physicians and the prescribing of brand-name as compared with generic statins for lowering cholesterol. Design, Setting, and Participants Cross-sectional linkage of the Part D Medicare prescriptions claims data with the Massachusetts physicians payment database including all licensed Massachusetts physicians who wrote prescriptions for statins paid for under the Medicare drug benefit in 2011. Main Outcomes and Measures The exposure variable was a physician’s industry payments as listed in the Massachusetts database. The outcome was the physician’s rate of prescribing brand-name statins. We used linear regression to analyze the association between the intensity of physicians’ industry relationships (as measured by total payments) and their prescribing practices, as well as the effects of specific types of payments. Results Among the 2444 Massachusetts physicians in the Medicare prescribing database in 2011, 899 (36.8%) received industry payments. The most frequent payment was for company-sponsored meals (n = 639 [71.1%]). Statins accounted for 1 559 003 prescription claims; 356 807 (22.8%) were for brand-name drugs. For physicians with no industry payments listed, the median brand-name statin prescribing rate was 17.8% (95% CI, 17.2%-18.4%). For every $1000 in total payments received, the brand-name statin prescribing rate increased by 0.1% (95% CI, 0.06%-0.13%; P P = .004); other forms of payments were not. Conclusions and Relevance Industry payments to physicians are associated with higher rates of prescribing brand-name statins. As the United States seeks to rein in the costs of prescription drugs and make them less expensive for patients, our findings are concerning.

In recent years, numerous US medical schools and academic medical centers have enacted policies preventing pharmaceutical sales representatives from interacting directly with students. Little is known about how pharmaceutical sales representatives affect trainees' knowledge about pharmaceutical prescribing.To determine whether there is an association between medical trainees' interactions with pharmaceutical promotion and their preferences in medication use.We surveyed a nationally representative sample of first- and fourth-year medical students and third-year residents by randomly selecting at least 14 trainees at each level per school.All trainees were asked how often they used different educational resources to learn about prescription drugs. Among fourth-year students and residents, we posed a series of multiple choice knowledge questions asking about the appropriate initial therapy for clinical scenarios involving patients with diabetes, hyperlipidemia, hypertension, and difficulty sleeping.Evidence-based answers followed widely used clinical guidelines, while marketed-drug answers favored brand-name drugs over generic alternatives. We used survey answers to build an industry relations index assessing each trainee's level of acceptance of pharmaceutical promotion; we used proportional odds logistic regression models to estimate the association between the index and responses to the knowledge questions.The 1601 student (49.0% response rate) and 735 resident (42.9% response rate) respondents reported common use of unfiltered sources of drug information such as Google (74.2%-88.9%) and Wikipedia (45.2%-84.5%). We found that 48% to 90% of fourth-year students and residents accurately identified evidence-based prescribing choices. A 10-point higher industry relations index was associated with 15% lower odds of selecting an evidence-based prescribing choice (odds ratio [OR], 0.85; 95% CI, 0.79-0.92) (P .001). There was also a significant association between the industry relations index and greater odds of choosing to prescribe brand-name drugs (OR, 1.08; 95% CI, 1.00-1.16) (P = .04).Among physician trainees, our survey showed an association between positive attitudes toward industry-physician interactions and less knowledge about evidence-based prescribing and greater inclination to recommend brand-name drugs. Policies intended to insulate trainees from pharmaceutical marketing may promote better educational outcomes.