Associations between specialty care and improved outcomes among patients with diabetic foot ulcers.

OBJECTIVE: Specialty care may improve diabetic foot ulcer outcomes. Medically underserved populations receive less specialty care. We aimed to determine the association between specialty care and ulcer progression, major amputation, or death. If a beneficial association is found, increasing access to specialty care might help advance health equity. RESEARCH DESIGN AND METHODS: We retrospectively analyzed a cohort of Wisconsin and Illinois Medicare patients with diabetic foot ulcers (n = 55,409), stratified by ulcer severity (i.e., early stage, osteomyelitis, or gangrene). Within each stratum, we constructed Kaplan-Meier curves for event-free survival, defining events as: ulcer progression, major amputation, or death. Patients were grouped based on whether they received specialty care from at least one of six disciplines: endocrinology, infectious disease, orthopedic surgery, plastic surgery, podiatry, and vascular surgery. Multivariate Cox proportional hazard models estimated the association between specialty care and event-free survival, adjusting for sociodemographic factors and comorbidities, and stratifying on ulcer severity. RESULTS: Patients who received specialty care had longer event-free survival compared to those who did not (log-rank p<0.001 for all ulcer severity strata). After adjusting, receipt of specialty care, compared to never, remained associated with improved outcomes for all ulcer severities (early stage adjusted hazard ratio 0.34, 95% CI 0.33-0.35, p<0.001; osteomyelitis aHR 0.22, 95% CI 0.20-0.23, p<0.001; gangrene aHR 0.22, 95% CI 0.20-0.24, p<0.001). CONCLUSIONS: Specialty care was associated with longer event-free survivals for patients with diabetic foot ulcers. Increased, equitable access to specialty care might improve diabetic foot ulcer outcomes and disparities.

Association of rurality and identifying as black with receipt of specialty care among patients hospitalized with a diabetic foot ulcer: a Medicare cohort study.

INTRODUCTION: Rural patients with diabetic foot ulcers, especially those identifying as black, face increased risk of major amputation. Specialty care can reduce this risk. However, care disparities might beget outcome disparities. We aimed to determine whether a smaller proportion of rural patients, particularly those identifying as black, receive specialty care compared with the national proportion. RESEARCH DESIGN AND METHODS: This 100% national retrospective cohort examined Medicare beneficiaries hospitalized with diabetic foot ulcers (2013-2014). We report observed differences in specialty care, including: endocrinology, infectious disease, orthopedic surgery, plastic surgery, podiatry, or vascular surgery. We used logistic regression to examine possible intersectionality between rurality and race, controlling for sociodemographics, comorbidities, and ulcer severity and including an interaction term between rurality and identifying as black. RESULTS: Overall, 32.15% (n=124 487) of patients hospitalized with a diabetic foot ulcer received specialty care. Among rural patients (n=13 100), the proportion decreased to 29.57%. For patients identifying as black (n=21 649), the proportion was 33.08%. Among rural patients identifying as black (n=1239), 26.23% received specialty care. This was >5 absolute percentage points less than the overall cohort. The adjusted OR for receiving specialty care among rural versus urban patients identifying as black was 0.61 (95% CI 0.53 to 0.71), which was lower than that for rural versus urban patients identifying as white (aOR 0.85, 95% CI 0.80 to 0.89). This metric supported a role for intersectionality between rurality and identifying as black. CONCLUSIONS: A smaller proportion of rural patients, particularly those identifying as black, received specialty care when hospitalized with a diabetic foot ulcer compared with the overall cohort. This might contribute to known disparities in major amputations. Future studies are needed to determine causality.

Using the National Institute on Minority Health and Health Disparities framework to better understand disparities in major amputations.

Recently, the United States experienced its first resurgence of major amputations in more than 20 years. Compounding this rise is a longstanding history of disparities. Patients identifying as non-Hispanic Black are twice as likely to lose a limb as those identifying as non-Hispanic White. Those identifying as Latino face a 30% increase. Rural patients are also more likely to undergo major amputations, and the rural-urban disparity is widening. We used the National Institute on Minority Health and Health Disparities framework to better understand these disparities and identify common factors contributing to them. Common factors were abundant and included increased prevalence of diabetes, possible lower rates of foot self-care, transportation barriers to medical appointments, living in disadvantaged neighborhoods, and lack of insurance. Solutions within and outside the health care realm are needed. Health care-specific interventions that embed preventative and ambulatory care services within communities may be particularly high yield.

Regional and racial disparities in major amputation rates among medicare beneficiaries with diabetes: a retrospective study in the southeastern USA.

Objective: While rates for non-traumatic lower extremity amputations (LEA) have been declining, concerns exist over disparities. Our objectives are to track major LEA (MLEA) rates over time among Medicare beneficiaries residing in a high diabetes prevalence region in the southeastern USA (the diabetes belt) and surrounding areas. Methods: We used Medicare claims files for ~900 000 fee-for-service beneficiaries aged ≥65 years in 2006-2015 to track MLEA rates per 1000 patients with diabetes. We additionally conducted a cross-sectional analysis of data for 2015 to compare regional and racial disparities in major amputation risks after adjusting for demographic, socioeconomic, access-to-care and foot complications and other health factors. The Centers for Disease Control and Prevention defined the diabetes belt as 644 counties across Appalachian and southeastern US counties with high prevalence. Results: MLEA rates were 3.9 per 1000 in the Belt compared with 2.8 in the surrounding counties in 2006 and decreased to 2.3 and 1.6 in 2015. Non-Hispanic black patients had 8.5 and 6.9 MLEAs per 1000 in 2006 and 4.8 and 3.5 in 2015 in the Belt and surrounding counties, respectively, while the rates were similar for non-Hispanic white patients in the two areas. Although amputation rates declined rapidly in both areas, non-Hispanic black patients in the Belt consistently had >3 times higher rates than non-Hispanic whites in the Belt. After adjusting for patient demographics, foot complications and healthcare access, non-Hispanic blacks in the Belt had about twice higher odds of MLEAs compared with non-Hispanic whites in the surrounding areas. Discussion: Our data show persistent disparities in major amputation rates between the diabetes belt and surrounding counties. Racial disparities were much larger in the Belt. Targeted policies to prevent MLEAs among non-Hispanic black patients are needed to reduce persistent disparities in the Belt.

Effect of health system on the association of rurality and level of disadvantage with receipt of diabetic eye screening.

INTRODUCTION: Rural versus urban disparities have been observed in diabetic eye screening, but whether the level of disadvantage in rural versus urban areas is related to these disparities is unclear. Our goal was to determine the role of level of disadvantage in explaining the effect of health systems on rural and urban disparities in diabetic eye screening. RESEARCH DESIGN AND METHODS: This is a retrospective cohort study using an all-payer, state-wide claims database covering over 75% of Wisconsin residents. We included adults with diabetes (18-75 years old) who had claims billed throughout the baseline (2012-2013) and measurement (2013-2014) years. We performed multivariable regressions to assess factors associated with receipt of diabetic eye screening. The primary exposure was the primary care clinic's combined level of rurality and disadvantage. We adjusted for the health system as well as patient-level variables related to demographics and comorbidities. Health system was defined as an associated group of physicians and/or clinics. RESULTS: A total of 118 707 adults with diabetes from 698 primary care clinics in 143 health systems met the inclusion criteria. Patients from urban underserved clinics were less likely to receive screening than those from rural underserved clinics before adjusting for health system in the model. After adjusting for health system fixed effects, however, the directionality of the relationship between clinic rurality and screening reversed: patients from urban underserved clinics were more likely to receive screening than those from rural underserved clinics. Similar findings were observed for both Medicare and non-Medicare subgroups. CONCLUSIONS: The effect of health system on receipt of diabetic eye screening in rural versus urban areas is most pronounced in underserved areas. Health systems, particularly those providing care to urban underserved populations, have an opportunity to increase screening rates by leveraging health system-level interventions to support patients in overcoming barriers from social determinants of health.

Ankle brachial indices and anaerobes: is peripheral arterial disease associated with anaerobic bacteria in diabetic foot ulcers?

Background: Lower extremity amputations from diabetic foot ulcers (DFUs) are rebounding, and new biomarkers that predict wound healing are urgently needed. Anaerobic bacteria have been associated with persistent ulcers and may be a promising biomarker beyond currently recommended vascular assessments. It is unknown whether anaerobic markers are simply a downstream outcome of peripheral arterial disease (PAD) and ischemia, however. Here, we evaluate associations between two measures of anaerobic bacteria-abundance and metabolic activity-and PAD. Methods: We built a prospective cohort of 37 patients with baseline ankle brachial index (ABI) results. Anaerobic bacteria were measured in two ways: DNA-based total anaerobic abundance using 16S rRNA gene amplicon sequencing and resulting summed relative abundance, and RNA-based metabolic activity based on bacterial read annotation of metatranscriptomic sequencing. PAD was defined three ways: PAD diagnosis, ABI results, and a dichotomous definition of mild ischemia (versus normal) based on ABI values. Statistical associations between anaerobes and PAD were evaluated using univariate odds ratios (ORs) or Spearman's correlations. Results: Total anaerobe abundance was not significantly associated with PAD diagnosis, ABI results, or mild ischemia (ORPAD = 0.47, 95% CI = 0.023-7.23, p = 0.60; Spearman's correlation coefficientABI = 0.24, p = 0.17; ORmild ischemia = 0.25, 95% CI = 0.005-5.86, p = 0.42). Anaerobic metabolic activity was not significantly associated with PAD diagnosis, ABI results, or mild ischemia (ORPAD = 1.99, 95% CI = 0.17-21.44, p = 0.57; Spearman's correlation coefficientABI = 0.12, p = 0.52; ORmild ischemia = 0.90, 95% CI = 0.03-15.16, p = 0.94). Conclusion: Neither anaerobic abundance nor metabolic activity was strongly associated with our three definitions of PAD. Therefore, anaerobic bacteria may offer additional prognostic value when assessing wound healing potential and should be investigated as potential molecular biomarkers for DFU outcomes.

Use of Novel Strategies to Develop Guidelines for Management of Pyogenic Osteomyelitis in Adults: A WikiGuidelines Group Consensus Statement.

Importance: Traditional approaches to practice guidelines frequently result in dissociation between strength of recommendation and quality of evidence. Objective: To construct a clinical guideline for pyogenic osteomyelitis management, with a new standard of evidence to resolve the gap between strength of recommendation and quality of evidence, through the use of a novel open access approach utilizing social media tools. Evidence Review: This consensus statement and systematic review study used a novel approach from the WikiGuidelines Group, an open access collaborative research project, to construct clinical guidelines for pyogenic osteomyelitis. In June 2021 and February 2022, authors recruited via social media conducted multiple PubMed literature searches, including all years and languages, regarding osteomyelitis management; criteria for article quality and inclusion were specified in the group's charter. The GRADE system for evaluating evidence was not used based on previously published concerns regarding the potential dissociation between strength of recommendation and quality of evidence. Instead, the charter required that clear recommendations be made only when reproducible, prospective, controlled studies provided hypothesis-confirming evidence. In the absence of such data, clinical reviews were drafted to discuss pros and cons of care choices. Both clear recommendations and clinical reviews were planned with the intention to be regularly updated as new data become available. Findings: Sixty-three participants with diverse expertise from 8 countries developed the group's charter and its first guideline on pyogenic osteomyelitis. These participants included both nonacademic and academic physicians and pharmacists specializing in general internal medicine or hospital medicine, infectious diseases, orthopedic surgery, pharmacology, and medical microbiology. Of the 7 questions addressed in the guideline, 2 clear recommendations were offered for the use of oral antibiotic therapy and the duration of therapy. In addition, 5 clinical reviews were authored addressing diagnosis, approaches to osteomyelitis underlying a pressure ulcer, timing for the administration of empirical therapy, specific antimicrobial options (including empirical regimens, use of antimicrobials targeting resistant pathogens, the role of bone penetration, and the use of rifampin as adjunctive therapy), and the role of biomarkers and imaging to assess responses to therapy. Conclusions and Relevance: The WikiGuidelines approach offers a novel methodology for clinical guideline development that precludes recommendations based on low-quality data or opinion. The primary limitation is the need for more rigorous clinical investigations, enabling additional clear recommendations for clinical questions currently unresolved by high-quality data.

Association of Race, Ethnicity, and Rurality With Major Leg Amputation or Death Among Medicare Beneficiaries Hospitalized With Diabetic Foot Ulcers.

Importance: Patients identifying as Black and those living in rural and disadvantaged neighborhoods are at increased risk of major (above-ankle) leg amputations owing to diabetic foot ulcers. Intersectionality emphasizes that the disparities faced by multiply marginalized people (eg, rural US individuals identifying as Black) are greater than the sum of each individual disparity. Objective: To assess whether intersecting identities of Black race, ethnicity, rural residence, or living in a disadvantaged neighborhood are associated with increased risk in major leg amputation or death among Medicare beneficiaries hospitalized with diabetic foot ulcers. Design, Setting, and Participants: This retrospective cohort study used 2013-2014 data from the US National Medicare Claims Data Database on all adult Medicare patients hospitalized with a diabetic foot ulcer. Statistical analysis was conducted from August 1 to October 27, 2021. Exposures: Race was categorized using Research Triangle Institute variables. Rurality was assigned using Rural-Urban Commuting Area codes. Residents of disadvantaged neighborhoods comprised those living in neighborhoods at or above the national 80th percentile Area Deprivation Index. Main Outcomes and Measures: Major leg amputation or death during hospitalization or within 30 days of hospital discharge. Logistic regression was used to explore interactions among race, ethnicity, rurality, and neighborhood disadvantage, controlling for sociodemographic characteristics, comorbidities, and ulcer severity. Results: The cohort included 124 487 patients, with a mean (SD) age of 71.5 (13.0) years, of whom 71 286 (57.3%) were men, 13 100 (10.5%) were rural, and 21 649 (17.4%) identified as Black. Overall, 17.6% of the cohort (n = 21 919), 18.3% of rural patients (2402 of 13 100), and 21.9% of patients identifying as Black (4732 of 21 649) underwent major leg amputation or died. Among 1239 rural patients identifying as Black, this proportion was 28.0% (n = 347). This proportion exceeded the expected excess for rural patients (18.3% - 17.6% = 0.7%) plus those identifying as Black (21.9% - 17.6% = 4.3%) by more than 2-fold (28.0% - 17.6% = 10.4% vs 0.7% + 4.3% = 5.0%). The adjusted predicted probability of major leg amputation or death remained high at 24.7% (95% CI, 22.4%-26.9%), with a significant interaction between race and rurality. Conclusions and Relevance: Rural patients identifying as Black had a more than 10% absolute increased risk of major leg amputation or death compared with the overall cohort. This study suggests that racial and rural disparities interacted, amplifying risk. Findings support using an intersectionality lens to investigate and address disparities in major leg amputation and mortality for patients with diabetic foot ulcers.

Good working relationships: how healthcare system proximity influences trust between healthcare workers.

Trust between healthcare workers is a fundamental component of effective, interprofessional collaboration and teamwork. However, little is known about how this trust is built, particularly when healthcare workers are distributed (i.e., not co-located and lack a shared electronic health record). We interviewed 39 healthcare workers who worked with proximal and distributed colleagues to care for patients with diabetic foot ulcers and analyzed transcripts using content analysis. Generally, building trust was a process that occurred over time, starting with an introduction and proceeding through iterative cycles of communication and working together to coordinate care for shared patients. Proximal, compared to distributed, dyads had more options available for interactions which, in turn, facilitated communication and working together to build trust. Distributed healthcare workers found it more difficult to develop trusting relationships and relied heavily on individual initiative to do so. Few effective tools existed at the level of interprofessional collaborations, teams, or broader healthcare systems to support trust between distributed healthcare workers. With increasing use of distributed interprofessional collaborations and teams, future efforts should focus on fostering this critical attribute.

COVID-19 in Health Care Personnel: Significance of Health Care Role, Contact History, and Symptoms in Those Who Test Positive for SARS-CoV-2 Infection.

OBJECTIVE: To identify significant factors that help predict whether health care personnel (HCP) will test positive for severe acute respiratory coronavirus 2 (SARS-CoV-2). PATIENTS AND METHODS: We conducted a prospective cohort study among 7015 symptomatic HCP from March 25, 2020, through November 11, 2020. We analyzed the associations between health care role, contact history, symptoms, and a positive nasopharyngeal swab SARS-CoV-2 polymerase chain reaction test results, using univariate and multivariable modelling. RESULTS: Of the symptomatic HCP, 624 (8.9%) were positive over the study period. On multivariable analysis, having a health care role other than physician or advanced practice provider, contact with family or community member with known or suspected coronavirus disease 2019 (COVID-19), and seven individual symptoms (cough, anosmia, ageusia, fever, myalgia, chills, and headache) were significantly associated with higher adjusted odds ratios for testing positive for SARS-CoV-2. For each increase in symptom number, the odds of testing positive nearly doubled (odds ratio, 1.93; 95% CI, 1.82 to 2.07, P<.001). CONCLUSION: Symptomatic HCP have higher adjusted odds of testing positive for SARS-CoV-2 based on three distinct factors: (1) nonphysician/advanced practice provider role, (2) contact with a family or community member with suspected or known COVID-19, and (3) specific symptoms and symptom number. Differences among health care roles, which persisted after controlling for contacts, may reflect the influence of social determinants. Contacts with COVID-19-positive patients and/or HCP were not associated with higher odds of testing positive, supporting current infection control efforts. Targeted symptom and contact questionnaires may streamline symptomatic HCP testing for COVID-19.

Expect delays: poor connections between rural and urban health systems challenge multidisciplinary care for rural Americans with diabetic foot ulcers.

BACKGROUND: Rural Americans with diabetic foot ulcers (DFUs) face a 50% increased risk of major amputation compared to their urban counterparts. We sought to identify health system barriers contributing to this disparity. METHODS: We interviewed 44 participants involved in the care of rural patients with DFUs: 6 rural primary care providers (PCPs), 12 rural specialists, 12 urban specialists, 9 support staff, and 5 patients/caregivers. Directed content analysis was performed guided by a conceptual model describing how PCPs and specialists collaborate to care for shared patients. RESULTS: Rural PCPs reported lack of training in wound care and quickly referred patients with DFUs to local podiatrists or wound care providers. Timely referrals to, and subsequent collaborations with, rural specialists were facilitated by professional connections. However, these connections often were lacking between rural providers and urban specialists, whose skills were needed to optimally treat patients with high acuity ulcers. Urban referrals, particularly to vascular surgery or infectious disease, were stymied by 1) time-consuming processes, 2) negative provider interactions, and 3) multiple, disconnected electronic health record systems. Such barriers ultimately detracted from rural PCPs' ability to focus on medical management, as well as urban specialists' ability to appropriately triage referrals due to lacking information. Subsequent collaboration between providers also suffered as a result. CONCLUSIONS: Poor connections across rural and urban healthcare systems was described as the primary health system barrier driving the rural disparity in major amputations. Future interventions focusing on mitigating this barrier could reduce the rural disparity in major amputations.

A systematic review of multidisciplinary teams to reduce major amputations for patients with diabetic foot ulcers.

OBJECTIVE: Multiple single-center studies have reported significant reductions in major amputations among patients with diabetic foot ulcers after initiation of multidisciplinary teams. The purpose of this study was to assess the association between multidisciplinary teams (ie, two or more types of clinicians working together) and the risk of major amputation and to compile descriptions of these diverse teams. METHODS: We searched PubMed, Scopus, Cumulative Index to Nursing and Allied Health, and Cochrane Central Register of Controlled Trials from inception through May 24, 2019 for studies reporting the association between multidisciplinary teams and major amputation rates for patients with diabetic foot ulcers. We included original studies if ≥50% of the patients seen by the multidisciplinary team had diabetes, they included a control group, and they reported the effect of a multidisciplinary team on major amputation rates. Studies were excluded if they were non-English language, abstracts only, or unpublished. We used the five-domain Systems Engineering Initiative for Patient Safety Model to describe team composition and function and summarized changes in major amputation rates associated with multidisciplinary team care. A meta-analysis was not performed because of heterogeneity across studies, their observational designs, and the potential for uncontrolled confounding (PROSPERO No. 2017: CRD42017067915). RESULTS: We included 33 studies, none of which were randomized trials. Multidisciplinary team composition and functions were highly diverse. However, four elements were common across teams: teams were composed of medical and surgical disciplines; larger teams benefitted from having a "captain" and a nuclear and ancillary team member structure; clear referral pathways and care algorithms supported timely, comprehensive care; and multidisciplinary teams addressed four key tasks: glycemic control, local wound management, vascular disease, and infection. Ninety-four percent (31/33) of studies reported a reduction in major amputations after institution of a multidisciplinary team. CONCLUSIONS: Multidisciplinary team composition was variable but reduced major amputations in 94% of studies. Teams consistently addressed glycemic control, local wound management, vascular disease, and infection in a timely and coordinated manner to reduce major amputation for patients with diabetic foot ulcerations. Care algorithms and referral pathways were key tools to their success.

The role of the microbiome in nonhealing diabetic wounds.

Wound healing is a highly coordinated and complex process, and there can be devastating consequences if it is interrupted. It is believed that, in combination with host factors, microorganisms in a wound bed can not only impair wound healing but can lead to stalled, chronic wounds. It is hypothesized that the wound microbiota persists in chronic wounds as a biofilm, recalcitrant to antibiotic and mechanical intervention. Cultivation-based methods are the gold standard for identification of pathogens residing in wounds. However, these methods are biased against fastidious organisms, and do not capture the full extent of microbial diversity in chronic wounds. Thus, the link between specific microbes and impaired healing remains tenuous. This is partially because local infection and, more specifically, the formation of a biofilm, is difficult to diagnose. This has led to research efforts aimed at understanding if biofilm formation delays healing and leads to persistent and chronic infection. Circumventing challenges associated with culture-based estimations, advances in high-throughput sequencing analysis has revealed that chronic wounds are host to complex, diverse microbiomes comprising multiple species of bacteria and fungi. Here, we discuss how the use of genomic methodologies to study wound microbiomes has advanced the current understanding of infection and biofilm formation in chronic wounds.

Increasing SBP variability is associated with an increased risk of developing incident diabetic foot ulcers.

OBJECTIVE: SBP variability may be a target for mitigating end-organ damage associated with vascular disease. We evaluated the relationship between increased SBP variability and risk of incident diabetic foot ulceration. METHODS: Using a nested case-control design, we followed patients diagnosed with diabetes and treated within the US Department of Veterans Affairs Healthcare system for development of a diabetic foot ulcer (event) between 2006 and 2010. Each case was randomly matched to up to five controls based on age, sex, race/ethnicity, and calendar time. SBP variability was computed using at least three blood pressure measurements from the year preceding the event. The association between SBP variability and foot ulceration was examined using conditional logistic regression. Potential protective effects of calcium channel blockers, which blunt SBP variability, were also explored. RESULTS: The study sample included 51 111 cases and 129 247 controls. Compared with those in quartile 1 (lowest variability), patients in quartiles 2-4 had higher adjusted odds ratios for diabetic foot ulcer development: 1.11 (95% CI 1.07-1.16), 1.20 (95% CI 1.15-1.25), 1.29 (95% CI 1.24-1.34) (P for trend <0.001). Calcium channel blockers were associated with reduced risks of ulceration for those without peripheral vascular disease (OR = 0.87, 95% CI 0.84-0.90, P < 0.001) or neuropathy (OR = 0.85, 95% CI 0.82-0.89, P < 0.001) in adjusted subgroup analyses. CONCLUSION: This study describes a graded relationship between SBP variability and risk of diabetic foot ulceration, providing a potential new and modifiable target to reduce this common complication.

Longitudinal trends and predictors of statin use among patients with diabetes.

AIM: Statins reduce morbidity and mortality among patients with diabetes, but their use remains suboptimal. Understanding trends in statin use may inform strategies for improvement. METHODS: We enrolled a national, retrospective cohort of 899,664 veterans aged≥40years with diabetes in 2003. We followed them through 2011, dividing the nine-year follow-up into 90-day periods. For each period, we determined statin use, defined as possession of ≥30-day supply. We examine factors associated with statin uptake among baseline non-users with a multivariate model. RESULTS: Baseline prevalence of statin use was 43%, increased by 1.8% per period (p for trend<0.001), and reached a maximum of ~59%. Statin use among non-Hispanic racial/ethnic minorities lagged behind their white counterparts. Among baseline non-users, statin use was 9% after Year 1 and reached 36% by Year 9. Factors associated with statin uptake included use of hypoglycemic agents, HbA1c between 7 and 8.9% (53-74mmol/mol), hypertension, heart failure, peripheral vascular disease, and Hispanic ethnicity. CONCLUSION: Statin use is slowly increasing among patients with diabetes, and at varying rates within subgroups of this population. Policies that prioritize these subgroups for statin promotion may help guide future, intervention-based research to increase compliance with current guidelines.

Non-small cell lung cancer clinical trials requiring biopsies with biomarker-specific results for enrollment provide unique challenges.

BACKGROUND: Clinical trials in lung cancer increasingly require patients to provide fresh tumor tissue as a prerequisite to enrollment. The effects of this requirement on enrollment rates, enrollment durations, and patient selection have not been fully elucidated. METHODS: The authors retrospectively reviewed data generated by patients who consented to 1 or more interventional lung cancer clinical trials at the University of California-Los Angeles Jonsson Comprehensive Cancer Center between January 2013 and December 2014. Trials were considered to require a biopsy when enrollment was conditional on the procurement of tissue without intervening therapy between procurement and enrollment. RESULTS: In total, 311 patients underwent 368 screening incidents for 1 or more of 19 trials. Trials that required a new biopsy had a longer median screening duration (34 vs 14 days) than trials that did not require a biopsy (P < .001). Trials that required a biopsy had a greater screen failure rate (49.1% vs 26.5%; P < .001), which was largely driven by patients who did not undergo the required biopsy or lacked the required biomarker. Worsening performance status led to the majority of screen failures (56.5%) among biomarker-eligible patients. CONCLUSIONS: Although the scientific benefits of obtaining a new biopsy and requiring specific results for trial enrollment are clear, these requirements lead to a lengthening of the screening period, which, in some patients, is associated with clinical decline before enrollment. Implications for the interpretation of data from studies of this design should be explored. Cancer 2017;123:4800-7. © 2017 American Cancer Society.