Challenging Assumptions About Minority Participation in US Clinical Research

Although extensive research addresses minorities’ low participation in clinical research, most focuses almost exclusively on therapeutic trials. The existing literature might mask important issues concerning minorities’ participation in clinical trials, and minorities might actually be overrepresented in phase I safety studies that require the participation of healthy volunteers. It is critical to consider the entire spectrum of clinical research when discussing the participation of disenfranchised groups; the literature on minorities’ distrust, poor access, and other barriers to trial participation needs reexamination. Minority participation in clinical trials is an important topic in public health discussions because this representation touches on issues of equality and the elimination of disparities, which are core values of the field

Burden Estimates, Post-diagnosis Care, and Outcomes Associated with Peripheral Artery Disease in the Atherosclerosis Risk in Communities Study

Peripheral artery disease (PAD) is a progressive atherosclerotic disorder of the lower extremities that causes adverse individual- and health care system-level consequences as populations age. This doctoral dissertation research estimated the annual period prevalence and incidence of PAD as well as the frequency of care and mortality following diagnosis in the outpatient or inpatient setting. The majority (>70%) of all PAD encounters occurred in the outpatient setting. The weighted mean age-standardized prevalence and incidence of outpatient PAD was 11.8% (95% CI: 11.5, 12.1) and 22.4 (95% CI: 20.8, 24.0) per 1000 person-years, respectively. Blacks had a higher mean weighted mean age-standardized prevalence (15.6%; 95% CI: 14.6, 16.4) as compared to whites (11.4%; 95% CI: 11.1, 11.7). Blacks also had a higher incidence rate of PAD (31.3 per 1000 person-years; 95% CI: 27.3, 35.4) as compared to whites (25.4 per 1000 person-years; 95% CI: 23.5, 27.3). PAD prevalence and incidence did not differ by gender alone. One-thousand eighty six incident cases of PAD were identified from 2002-2010. PAD-related post-diagnosis encounters were 2.15 (95% CI: 2.10, 2.21) and 1.02 (95% CI: 0.94, 1.10) among those with an incident PAD diagnosis in the outpatient and inpatient setting, respectively. Participants with PAD had an average of 6-8 primary care encounters per person-year over the course of our study. PAD-related and all-cause hospitalization was 6.4% (95% CI: 4.8, 8.1) and 32.2% (95% CI: 29.0, 35.2) at one year among those with incident outpatient PAD. Approximately 14% (95% CI: 9.3, 18.7) of participants diagnosed with inpatient PAD had a PAD-related rehospitalization at one year while 43.4% (95% CI: 36.3, 49.7) had an all-cause rehospitalization at one year. One year age-standardized case fatality was 7.1% (95% CI: 5.4, 8.7) and 16.0% (95% CI: 11.0, 21.1) among those diagnosed in the outpatient and inpatient setting, respectively. Peripheral artery disease and utilization of outpatient health care services was common among men and women 65 years of age and older with enrollment in a Medicare fee-for-service program sampled of four US communities.Doctor of Philosoph

Altruism in clinical research: Coordinators’ orientation to their professional roles

Research coordinators have significant responsibilities in clinical trials that often require them to find unique ways to manage their jobs, thus re-shaping their professional identities

United States Private-Sector Physicians and Pharmaceutical Contract Research: A Qualitative Study

There have been dramatic increases over the past 20 years in the number of nonacademic, private-sector physicians who serve as principal investigators on US clinical trials sponsored by the pharmaceutical industry. However, there has been little research on the implications of these investigators' role in clinical investigation. Our objective was to study private-sector clinics involved in US pharmaceutical clinical trials to understand the contract research arrangements supporting drug development, and specifically how private-sector physicians engaged in contract research describe their professional identities

Peering into the pharmaceutical “pipeline”: Investigational drugs, clinical trials, and industry priorities

In spite of a growing literature on pharmaceuticalization, little is known about the pharmaceutical industry’s investments in research and development (R&D). Information about the drugs being developed can provide important context for existing case studies detailing the expanding – and often problematic – role of pharmaceuticals in society. To access the pharmaceutical industry’s pipeline, we constructed a database of drugs for which pharmaceutical companies reported initiating clinical trials over a five-year period (July 2006-June 2011), capturing 2,477 different drugs in 4,182 clinical trials. Comparing drugs in the pipeline that target diseases in high-income and low-income countries, we found that the number of drugs for diseases prevalent in high-income countries was 3.46 times higher than drugs for diseases prevalent in low-income countries. We also found that the plurality of drugs in the pipeline were being developed to treat cancers (26.2%). Interpreting our findings through the lens of pharmaceuticalization, we illustrate how investigating the entire drug development pipeline provides important information about patterns of pharmaceuticalization that are invisible when only marketed drugs are considered

Peripheral Artery Disease Prevalence and Incidence Estimated From Both Outpatient and Inpatient Settings Among Medicare Fee‐for‐Service Beneficiaries in the Atherosclerosis Risk in Communities (ARIC) Study

BACKGROUND: Outpatient ascertainment of peripheral artery disease (PAD) is rarely considered in the measurement of PAD clinical burden; therefore, the clinical burden of PAD likely has been underestimated while contributing to a decreased awareness of PAD in comparison to other circulatory system disorders. METHODS AND RESULTS: The purpose of this study was to estimate the age-standardized annual period prevalence and incidence of PAD in the outpatient and inpatient settings using data from the Atherosclerosis Risk in Communities (ARIC) study linked with Centers for Medicare and Medicaid Services claims. The majority (>70%) of all PAD encounters occurred in the outpatient setting. The weighted mean age-standardized prevalence and incidence of outpatient PAD was 11.8% (95% CI 11.5-12.1) and 22.4 per 1000 person-years (95% CI 20.8-24.0), respectively. Black patients had higher weighted mean age-standardized prevalence (15.6%; 95% CI 14.6-16.4) compared with white patients (11.4%; 95% CI 11.1-11.7). Black women had the highest weighted mean age-standardized prevalence (16.9%; 95% CI 16.0-17.8). Black patients also had a higher incidence rate of PAD (31.3 per 1000 person-years; 95% CI 27.3-35.4) compared with white patients (25.4 per 1000 person-years; 95% CI 23.5-27.3). PAD prevalence and incidence did not differ by sex alone. CONCLUSIONS: This study provides comprehensive estimates of PAD in the inpatient and outpatient settings where the majority of PAD burden was found. PAD is an important circulatory system disorder similar in prevalence to stroke and coronary heart disease

Ankle-brachial index and physical function in older individuals: The Atherosclerosis Risk in Communities (ARIC) study

Most prior studies investigating the association of lower extremity peripheral artery disease (PAD) with physical function were small or analyzed selected populations (e.g., patients at vascular clinics or persons with reduced function), leaving particular uncertainty regarding the association in the general community

Preoperative clinical factors predict postoperative functional outcomes after major lower limb amputation: An analysis of 553 consecutive patients

BackgroundDespite being a major determinant of functional independence, ambulation after major limb amputation has not been well studied. The purpose, therefore, of this study was to investigate the relationship between a variety of preoperative clinical characteristics and postoperative functional outcomes in order to formulate treatment recommendations for patients requiring major lower limb amputation.MethodsFrom January 1998 through December 2003, 627 major limb amputations (37.6% below knee amputations, 4.3% through knee amputations, 34.5% above knee amputations, and 23.6% bilateral amputations) were performed on 553 patients. Their mean age was 63.7 years; 55% were men, 70.2% had diabetes mellitus, and 91.5% had peripheral vascular disease. A retrospective review was performed correlating various preoperative presenting factors such as age at presentation, race, medical comorbidities, preoperative ambulatory status, and preoperative independent living status, with postoperative functional endpoints of prosthetic usage, survival, maintenance of ambulation, and maintenance of independent living status. Kaplan-Meier survival curves were constructed and compared by using the log-rank test. Odds ratios (OR) and hazard ratios (HR) with 95% confidence intervals were constructed by using multiple logistic regressions and Cox proportional hazards models.ResultsStatistically significant preoperative factors independently associated with not wearing a prosthesis in order of greatest to least risk were nonambulatory before amputation (OR, 9.5), above knee amputation (OR, 4.4), age >60 years (OR, 2.7), homebound but ambulatory status (OR, 3.0), presence of dementia (OR, 2.4), end-stage renal disease (OR, 2.3), and coronary artery disease (OR, 2.0). Statistically significant preoperative factors independently associated with death in decreasing order of influence included age ≥70 years (HR, 3.1), age 60 to 69 (HR, 2.5), and the presence of coronary artery disease (HR, 1.5). Statistically significant preoperative factors independently associated with failure of ambulation in decreasing order of influence included age ≥70 years (HR, 2.3), age 60 to 69 (HR, 1.6), bilateral amputation (HR, 1.8), and end-stage renal disease (HR, 1.4). Statistically significant preoperative factors independently associated with failure to maintain independent living status in decreasing order of influence included age ≥70 years (HR, 4.0), age 60 to 69 (HR, 2.7), level of amputation (HR, 1.8), homebound ambulatory status (HR, 1.6), and the presence of dementia (HR, 1.6).ConclusionsPatients with limited preoperative ambulatory ability, age ≥70, dementia, end-stage renal disease, and advanced coronary artery disease perform poorly and should probably be grouped with bedridden patients, who traditionally have been best served with a palliative above knee amputation. Conversely, younger healthy patients with below knee amputations achieved functional outcomes similar to what might be expected after successful lower extremity revascularization. Amputation in these instances should probably not be considered a failure of therapy but another treatment option capable of extending functionality and independent living

Characteristics and Outcomes of Patients With Acute Decompensated Heart Failure Developing After Hospital Admission

There are limited data on ADHF that develops after hospital admission. This study sought to compare patient characteristics, comorbidities, mortality, and length of stay by timing of acute decompensated heart failure (ADHF) onset. The surveillance component of the Atherosclerosis Risk in Communities Study (2005–2011) sampled, abstracted, and adjudicated hospitalizations with select ICD-9-CM discharge codes from 4 U.S. communities among those aged 55 years and older. We included 5,602 validated ADHF hospitalizations further classified as pre- or post-admission onset. Vital status was assessed up to 1 year since admission. We estimated multivariable-adjusted associations of in-hospital mortality, 28-day case fatality, and 365-day case fatality with timing of ADHF onset (post-versus pre-admission). All analyses were weighted to account for the stratified sampling design. Of 25,862 weighted ADHF hospitalizations, 7% had post-admission onset of ADHF. Patients with post-admission ADHF were more likely to be older, white, and female. The most common primary discharge diagnosis codes for those with post-admission ADHF included diseases of the circulatory or digestive systems or infectious diseases. Short-term mortality among post-admission ADHF was almost 3 times that of pre-admission ADHF (in-hospital mortality: odds ratio: 2.7, 95% confidence interval: 1.9–3.9; 28-day case fatality: odds ratio: 2.6, 95% confidence interval: 1.8–3.7). The average hospital stay was almost twice as long among post-admission as pre-admission ADHF (9.6 vs. 5.0 days). In conclusion, post-admission onset of ADHF is characterized by differences in comorbidities and worse short-term prognosis, and opportunities for reducing post-admission ADHF occurrence and associated risks need to be studied

Efficacy of Messenger RNA-1273 Against Severe Acute Respiratory Syndrome Coronavirus 2 Acquisition in Young Adults From March to December 2021

BACKGROUND: The efficacy of messenger RNA (mRNA)-1273 against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is not well defined, particularly among young adults. METHODS: Adults aged 18-29 years with no known history of SARS-CoV-2 infection or prior vaccination for coronavirus disease 2019 (COVID-19) were recruited from 44 US sites from 24 March to 13 September 2021 and randomized 1:1 to immediate vaccination (receipt of 2 doses of mRNA-1273 vaccine at months 0 and 1) or the standard of care (receipt of COVID-19 vaccine). Randomized participants were followed up for SARS-CoV-2 infection measured by nasal swab testing and symptomatic COVID-19 measured by nasal swab testing plus symptom assessment and assessed for the primary efficacy outcome. A vaccine-declined observational group was also recruited from 16 June to 8 November 2021 and followed up for SARS-CoV-2 infection as specified for the randomized participants. RESULTS: The study enrolled 1149 in the randomized arms and 311 in the vaccine-declined group and collected >122 000 nasal swab samples. Based on randomized participants, the efficacy of 2 doses of mRNA-1273 vaccine against SARS-CoV-2 infection was 52.6% (95% confidence interval, -14.1% to 80.3%), with the majority of infections due to the Delta variant. Vaccine efficacy against symptomatic COVID-19 was 71.0% (95% confidence interval, -9.5% to 92.3%). Precision was limited owing to curtailed study enrollment and off-study vaccination censoring. The incidence of SARS-CoV-2 infection in the vaccine-declined group was 1.8 times higher than in the standard-of-care group. CONCLUSIONS: mRNA-1273 vaccination reduced the incidence of SARS-CoV-2 infection from March to September 2021, but vaccination was only one factor influencing risk. CLINICAL TRIALS REGISTRATION: NCT04811664