Corey A. Kalbaugh

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

Jill Fisher and Corey Kalbaugh describe their findings from a qualitative research study evaluating the motivations of private-sector physicians conducting contract research for the pharmaceutical industry.

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 industrys 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 industrys 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 2477 different drugs in 4182 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 was 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.

Altruism in Clinical Research: Coordinators’ Orientation to their Professional Roles

OBJECTIVE Research coordinators have significant responsibilities in clinical trials that often require them to find unique ways to manage their jobs, thus reshaping their professional identities. The purpose of this study was to identify how research coordinators manage role and ethical conflicts within clinical research trials. METHODS A qualitative study combining observation and 63 semistructured interviews at 25 research organizations was used. RESULTS Altruism is a recurring theme in how research coordinators define and view their work. CONCLUSION Altruism is adopted by research coordinators to: (1) Teach patient-subjects the appropriate reasons to participate in clinical research, (2) minimize the conflict between research and care, and (3) contest the undervaluation of coordinating. Altruism is a strategy used to handle the various conflicts they experience in a difficult job, and it has become part of the professional identity of clinical research coordinators.

Current accepted hemodynamic criteria for critical limb ischemia do not accurately stratify patients at high risk for limb loss

OBJECTIVE Critical limb ischemia (CLI) has been defined as rest pain or tissue loss in patients who have an ankle-brachial index (ABI) ≤0.50, ankle pressure (AP) <70 mm Hg, or toe pressure (TP) <50 mm Hg. Data suggesting that these patients are at high risk for limb loss without successful revascularization are limited. This study was designed to identify limb loss and mortality rates in patients who did not respond to revascularization or who were not revascularized to determine whether CLI hemodynamic criteria accurately identify patients at high risk for limb loss. METHODS Between 2008 and 2010, all patients undergoing lower extremity arterial duplex ultrasound testing at our hospital were identified. Those with ABI <0.50, AP <70 mm Hg, or TP <50 mm Hg were retrospectively reviewed to determine whether they had symptoms of rest pain, ischemic ulceration, or gangrene qualifying them for analysis in the database. Patients who underwent revascularization and subsequently had postrevascularization ABI, AP, or TP greater than the CLI criteria were removed from the cohort. Demographic factors, wound healing, amputation rates, and mortality were obtained and analyzed in relation to the initial APs and TPs. Outcomes were measured by Kaplan-Meier life-table analysis and Cox proportional hazards models. RESULTS In 381 patients identified in the study, 443 limbs met CLI criteria. After revascularization, 98 limbs with ABI or TP that improved to >0.5 and >50 mm Hg, respectively, were removed from the study cohort. In 45 limbs, patients did not respond to initial revascularization as their ABI, AP, or TP remained within CLI criteria. These limbs remained in the patient cohort, yielding a final group of 296 patients and 345 limbs. Mean follow-up was 2 years. In the entire patient cohort, limb loss occurred in 24% at 1 year and in 31% at 3 years. Mortality was 32% at 1 year and 56% at 3 years. Amputation-free survival was 54% at 1 year and 28% at 3 years. Lower TPs were associated with a statistically higher incidence of amputation. Among those with an initial TP ≤10 mm Hg (n = 85), limb loss occurred in 46% at 1 year and 60% at 3 years. This limb loss was significantly greater than limb loss among those with a TP of 31 to 50 mm Hg (n = 115; 18% at 3 years; P < .001) Amputation-free survival in patients with a TP ≤10 mm Hg was 8% at 3 years. CONCLUSIONS CLI is associated with a high mortality, but not all patients with currently defined hemodynamic criteria for CLI are at high risk of limb loss. Patients with a TP between 31 and 50 mm Hg (41% of the cohort) and not receiving revascularization or not responding hemodynamically to revascularization experienced a low risk of limb loss. We recommend revising the hemodynamic criteria for CLI to better identify patients at high risk for limb loss who require intervention to improve outcomes.

Living in a medically underserved county is an independent risk factor for major limb amputation

OBJECTIVE Despite an increase in the incidence of hospital admissions for comorbid conditions, such as diabetes, the incidence of major limb amputation in North Carolina has decreased. The decline in amputation rate has not been uniformly realized across the state. The objective of this study was to determine the association between major vascular limb amputation and living in an underserved county in North Carolina. METHODS We analyzed discharges aged 18 to 100 years old with a peripheral arterial disease (PAD)-related admission from the North Carolina Inpatient Discharge Database from 2006 to 2009. Medically underserved counties are defined by the United States Health Resources and Services Administration as having too few primary care providers, high infant mortality, high poverty, or high elderly population. The association between major amputation prevalence and medically underserved counties was calculated using a binomial regression model adjusted for sex, age, diabetes, end-stage renal disease, PAD, and critical limb ischemia. Each confounder was assessed using backward elimination modeling. RESULTS Among the 222,920 discharges with a PAD-related hospital admission from 2006 to 2009, 8601 (3.9%) were from medically underserved counties. There were 7328 major amputations. The adjusted prevalence odds ratio of the association between underserved counties and major vascular limb amputation is 1.29 (95% confidence interval, 1.16-1.44). None of the confounders significantly affected the association between underserved counties and number of amputations. CONCLUSIONS Living in an underserved county in North Carolina is associated with a 29% increase in the odds of undergoing major limb amputation. Gender, age, and comorbidities, including diabetes, end-stage renal disease, and PAD, do not significantly affect the relationship.

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

BACKGROUND AND AIMS 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. METHODS Among 5262 ARIC participants (age 71-90 years during 2011-2013), we assessed the cross-sectional association of ankle-brachial index (ABI) with the Short Physical Performance Battery (SPPB) score (0-12), its individual components (chair stands, standing balance, and gait speed) (0-4 points each), and grip strength after accounting for potential confounders, including a history of coronary disease, stroke, or heart failure. RESULTS There were 411 participants (7.8%) with low ABI ≤0.90 and 469 (8.9%) participants with borderline low ABI 0.91-1.00. Both ABI ≤0.90 and 0.91-1.00 were independently associated with poor physical function (SPPB score ≤6) compared to ABI 1.11-1.20 (adjusted odds ratio 2.10 [95% CI 1.55-2.84] and 1.86 [1.38-2.51], respectively). The patterns were largely consistent across subgroups by clinical conditions (e.g., leg pain or other cardiovascular diseases), in every SPPB component, and for grip strength. ABI >1.3 (472 participants [9.0%]), indicative of non-compressible pedal arteries, was related to lower physical function as well but did not necessarily reach significance. CONCLUSIONS In community-dwelling older adults, low and borderline low ABI suggestive of PAD were independently associated with poorer systemic physical function compared to those with normal ABI. Clinical attention to PAD as a potential contributor to poor physical function is warranted in community-dwelling older adults.

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.

The impact of current smoking on outcomes after infrainguinal bypass for claudication

Objective: Although smoking cessation is a benchmark of medical management of intermittent claudication, many patients require further revascularization. Currently, revascularization among smokers is a controversial topic, and practice patterns differ institutionally, regionally, and nationally. Patients who smoke at the time of revascularization are thought to have a poor prognosis, but data on this topic are limited. The purpose of this study was to evaluate the impact of smoking on outcomes after infrainguinal bypass for claudication. Methods: Data from the national Vascular Quality Initiative from 2004 to 2014 were used to identify infrainguinal bypasses performed for claudication. Patients were categorized as former smokers (quit >1 year before intervention) and current smokers (smoking within 1 year of intervention). Demographic and comorbid differences of categorical variables were assessed. Significant predictors were included in adjusted Cox proportional hazards models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) by smoking status for outcomes of major adverse limb event (MALE), amputation‐free survival, limb loss, death, and MALE or death. Cumulative incidence curves were created using competing risks modeling. Results: We identified 2913 patients (25% female, 9% black) undergoing incident infrainguinal bypass grafting for claudication. There were 1437 current smokers and 1476 former smokers in our study. Current smoking status was a significant predictor of MALE (HR, 1.27; 95% CI, 1.00‐1.60; P = .048) and MALE or death (HR, 1.22; 95% CI, 1.03‐1.44; P = .02). Other factors found to be independently associated with poor outcomes in adjusted models included black race, below‐knee bypass grafting, use of prosthetic conduit, and dialysis dependence. Conclusions: Current smokers undergoing an infrainguinal bypass procedure for claudication experienced more MALEs than former smokers did. Future studies with longer term follow‐up should address limitations of this study by identifying a data source with long‐term follow‐up examining the relationship of smoking exposure (pack history and duration) with outcomes.

Tracking the Pharmaceutical Pipeline: Clinical Trials and Global Disease Burden

Aggregate data about pharmaceutical research and development (R&D) tend to examine Phase III trials. Hence, there are few published data about investigational drugs in earlier phases of clinical development that might fail. It is also unclear how well R&D corresponds to disease burden. We track the pharmaceutical pipeline using data from industry publications that provide otherwise unreported information about industry‐sponsored clinical trials. The sample includes 2,477 unique drug entities in 4,182 clinical trials. The majority of drugs targeted neoplasms (26.20%), neurological diseases/diseases of the sense organs (13.48%), infectious and parasitic diseases (10.5%), and endocrine, metabolic, nutrition, and immunity disorders (9.45%). Less than 6% of drugs targeted diseases of the circulatory system, which represent the most prevalent causes of global mortality. Detailing the pharmaceutical pipeline, our findings suggest that pharmaceutical development does not adequately address global disease burden. Future research on the under‐reported details of Phase I and II clinical trials is needed to understand how the industry operates and how its resource‐allocation matches global health concerns.

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

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