Eligible Patient Population Research Articles

Stroke Treatment Academic Industry Roundtable: The Next Generation of Endovascular Trials.

The STAIR (Stroke Treatment Academic Industry Roundtable) meeting aims to advance acute stroke therapy development through collaboration between academia, industry, and regulatory institutions. In pursuit of this goal and building on recently available level I evidence of benefit from endovascular therapy (ET) in large vessel occlusion stroke, STAIR IX consensus recommendations were developed that outline priorities for future research in ET. Three key directions for advancing the field were identified: (1) development of systems of care for ET in large vessel occlusion stroke, (2) development of therapeutic approaches adjunctive to ET, and (3) exploring clinical benefit of ET in patient population insufficiently studied in recent trials. Methodological issues such as optimal trial design and outcome measures have also been addressed. Development of systems of care strategies should be geared both toward ensuring broad access to ET for eligible patients and toward shortening time to reperfusion to the minimum possible. Adjunctive therapy development includes neuroprotective approaches, adjuvant microcirculatory/collateral enhancing strategies, and periprocedural management. Future research priorities seeking to expand the eligible patient population are to determine benefit of ET in patients presenting beyond conventional time windows, in patients with large baseline ischemic core lesions, and in other important subgroups. Research priorities in ET for large vessel occlusion stroke are to improve systems of care, investigate effective adjuvant therapies, and explore whether patient eligibility could be expanded.

Evaluation of a Potential Interaction Between New Regimens to Treat Hepatitis C and Warfarin.

New regimens to treat hepatitis C virus infection have expanded the eligible patient population to include more patients receiving concurrent warfarin. The primary objective of this study was to assess whether a drug interaction occurs when these regimens are added to warfarin therapy. This was a retrospective cohort design using a nationwide database of the Veterans Affairs Health System. Patients on warfarin therapy treated with sofosbuvir or ombitasvir, paritaprevir-ritonavir, and dasabuvir (OBV-PTV/r-DSV) from March 2014 through October 2015 were identified. The warfarin dose response was calculated using a warfarin sensitivity index (WSI) defined as the steady-state INR divided by the mean daily warfarin dose. The primary outcome was the change in WSI from hepatitis C treatment initiation to completion. The final sample consisted of 271 patients. The WSI decreased 23% from a mean baseline value of 0.53 to 0.39 (decrease of 0.14; 95% CI = 0.11 to 0.16; P < 0.001). OBV-PTV/r-DSV produced a significantly greater decrease than any sofosbuvir regimen. Concurrent ribavirin accounted for an additional decrease in warfarin sensitivity of -0.09 (95% CI = -0.06 to -0.12; P < 0.001). The percentage of subtherapeutic INR results increased from 26% prior to hepatitis C treatment to 58% during treatment. Results indicate a clinically significant reduction in warfarin dose-response when hepatitis C treatment regimens were added to warfarin. They were most profound with OBV-PTV/r-DSV. Ribavirin was associated with an additive effect. Clinicians should be aware of this potential drug interaction to closely monitor and minimize subtherapeutic levels of anticoagulation.

Ivabradine: Role in the Chronic Heart Failure Armamentarium.

Ivabradine is approved to reduce hospitalizations for patients with symptomatic heart failure, reduced ejection fraction, and persistently elevated heart rate despite otherwise maximal medical therapy. However, the eligible patient population is a small fraction of those with heart failure overall. This review summarizes the major clinical evidence supporting the use of ivabradine, identifies and discusses areas of uncertainty from the clinical trial data, helps describe the population most likely to benefit, and attempts to place ivabradine within the multifaceted treatment scheme currently used for patients with heart failure and reduced ejection fraction.

PCN82 - An Investigation of the Correlation Between Price and Eligible Patient Population Size for Lung Cancer Products Available in the United States

PCN82 - An Investigation of the Correlation Between Price and Eligible Patient Population Size for Lung Cancer Products Available in the United States

Implementing Routine HIV Screening in Three Chicago Hospitals: Lessons Learned.

This study describes routine HIV screening implementation and outcomes in three hospitals in Chicago, Illinois. Retrospective data from three hospitals were examined, and routine testing procedures, testing volume, reactive test results, and linkage-to-care outcomes were documented. From January 2012 through March 2014, 40,788 HIV tests were administered at the three hospitals: 18,603 (46%) in the emergency department (ED), 7,546 (19%) in the inpatient departments, and 14,639 (36%) in outpatient clinics. The screened patients varied from 1% to 22% of the total eligible patient population across hospitals. A total of 297 patients tested positive for HIV for a seropositivity rate of 0.7%; 129 (43%) were newly diagnosed and 168 (57%) were previously diagnosed, with 64% of those previously diagnosed out of care at the time of screening. The inpatient areas had the highest seropositivity rate (0.6%). The percentage of newly diagnosed patients overall who were linked to care was 77%. Of newly diagnosed patients, 51% had ≥ 1 missed opportunity for testing (with a mean of 3.8 visits since 2006), and 30% of patients with missed opportunities were late testers (baseline CD4+ counts <200 cells per cubic millimeter). Routine screening is an essential tool for identifying new infections and patients with known infection who are out of care. Hospitals need to provide HIV screening in inpatient and outpatient settings--not just EDs--to decrease missed opportunities. Routine screening success will be driven by how notification and testing are incorporated into the normal medical flow, the level of leadership buy-in, the ability to conduct quality assurance, and local testing laws.

Correction of murine hemoglobinopathies by prenatal tolerance induction and postnatal nonmyeloablative allogeneic BM transplants

AbstractSickle cell disease (SCD) and thalassemias (Thal) are common congenital disorders, which can be diagnosed early in gestation and result in significant morbidity and mortality. Hematopoietic stem cell transplantation, the only curative therapy for SCD and Thal, is limited by the absence of matched donors and treatment-related toxicities. In utero hematopoietic stem cell transplantation (IUHCT) is a novel nonmyeloablative transplant approach that takes advantage of the immunologic immaturity and normal developmental properties of the fetus to achieve mixed allogeneic chimerism and donor-specific tolerance (DST). We hypothesized that a combined strategy of IUHCT to induce DST, followed by postnatal nonmyeloablative same donor “booster” bone marrow (BM) transplants in murine models of SCD and Thal would result in high levels of allogeneic engraftment and donor hemoglobin (Hb) expression with subsequent phenotypic correction of SCD and Thal. Our results show that: (1) IUHCT is associated with DST and low levels of allogeneic engraftment in the murine SCD and Thal models; (2) low-level chimerism following IUHCT can be enhanced to high-level chimerism and near complete Hb replacement with normal donor Hb with this postnatal “boosting” strategy; and (3) high-level chimerism following IUHCT and postnatal “boosting” results in phenotypic correction in the murine Thal and SCD models. This study supports the potential of IUHCT, combined with a postnatal nonmyelablative “boosting” strategy, to cure Thal and SCD without the toxic conditioning currently required for postnatal transplant regimens while expanding the eligible transplant patient population due to the lack of a restricted donor pool.

Availability and payer coverage of BRCA1/2 tests and gene panels.

Availability and payer coverage of BRCA1/2 tests and gene panels.

Implementing Guidelines: The Cost and Clinical Impact of Anticoagulants in the UK Atrial Fibrillation Population.

Updated treatment guidelines for atrial fibrillation (AF) have been released by the National Institute for Health and Care Excellence (NICE) in the UK, and highlight a current shortfall in the prescription of anticoagulants to patients with AF for stroke prevention. To design a budget impact model as a planning tool for UK Clinical Commissioning Groups (CCGs) looking to budget for greater use of anticoagulants in the AF population. An Excel® model was developed to estimate the five-year impact of gradually treating all eligible patients with AF who are currently not being prescribed anticoagulants, both in terms of the effect on key clinical outcomes (strokes, major bleeds and mortality) and the associated financial impact. For a population of 251,693 (average CCG size) with an estimated 2626 prevalent patients and an additional 546 incident cases annually, the model estimated that increasing the proportion of the eligible AF patient population receiving anticoagulation by a fraction would require an additional budget of GBP139,961 in Year 1 to treat an additional 314 patients. This would rise to GBP1,004,900 in Year 5 to treat an additional 2242 patients, with all eligible patients treated by this year. The price year was 2014. Over the 5-year timeframe, this could lead to the prevention of 24 strokes and 29 deaths, with an increase of 31 major bleeds. The clinical benefits of appropriate anticoagulation are widely recognised; however, full implementation can be difficult and costly. Therefore, the development of models can support the planning process by facilitating discussion among stakeholders on how best they can reach full implementation. The model is flexible and can be adapted to suit different payers.

Clinical utility estimation for assay cutoffs in early phase oncology enrichment trials.

Predictive enrichment strategies use biomarkers to selectively enroll oncology patients into clinical trials to more efficiently demonstrate therapeutic benefit. Because the enriched population differs from the patient population eligible for screening with the biomarker assay, there is potential for bias when estimating clinical utility for the screening eligible population if the selection process is ignored. We write estimators of clinical utility as integrals averaging regression model predictions over the conditional distribution of the biomarker scores defined by the assay cutoff and discuss the conditions under which consistent estimation can be achieved while accounting for some nuances that may arise as the biomarker assay progresses toward a companion diagnostic. We outline and implement a Bayesian approach in estimating these clinical utility measures and use simulations to illustrate performance and the potential biases when estimation naively ignores enrichment. Results suggest that the proposed integral representation of clinical utility in combination with Bayesian methods provide a practical strategy to facilitate cutoff decision-making in this setting.

Multimodal assessment of choroideremia patients defines pre-treatment characteristics.

Choroideremia (CHM) is a X-chromosomal disorder leading to blindness by progressive degeneration of choroid, retinal pigment epithelium (RPE), and retinal neurons. A current clinical gene therapy trial (NCT01461213) showed promising safety and efficacy data in a carefully selected patient population. The present study was performed to shed light on pre-treatment characteristics of a larger cohort of CHM patients using a high resolutionmulti-modal approach. In a retrospective cross-sectional study, data from 58 eyes of 29 patients with clinically confirmed CHM were analysed including best-corrected visual acuity (BCVA), refractive error, spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF), perimetry, and tonometry. Residual retinal volume, area of residual RPE, and foveal thickness were quantified to further define natural disease progression and assess symmetry. We evaluated 98 data points of BCVA [0.34 ± 0.06 (logMAR); mean ± 95% confidence interval], 80 of IOP (14.6 ± 0.6mmHg), and 98 of refraction (-2.16 ± 1.08 spherical equivalent). Visual fields (n = 76) demonstrated variable degrees of concentric constriction (54% <10°, 25% 10-30°, 21% >30°). Mean residual RPE area on FAF (n = 64) measured 8.47 ± 1.91mm(2) (range 0.30-38.5mm(2)), while mean neuroretinal volume (n = 42) was found to be 1.76 ± 0.12mm(3). Age at examination was exponentially associated with BCVA, while logarithmic functions best described progressive loss of retinal area and volume. A high degree of left to right symmetry was found in all modalities with structural markers showing the best correlation (r (2) area = 0.83; r (2) volume = 0.75). Analysis of these widely available clinical data defines the natural disease characteristics of a relevant patient population eligible for gene therapeutic intervention. In the wake of preliminary reports on safety and efficacy of CHM gene therapy (NCT01461213), this multi-modal assessment of a cohort of CHM patients provides important evidence of the natural rate of disease progression and degree of symmetry between eyes.

O11.3 - Targeting isocitrate dehydrogenase (IDH)1 and IDH2 mutations Clinical results in advanced hematologic malignancies

ABSTRACT Cancer metabolism represents an emerging field of novel cancer target discovery. Somatic point mutations in the metabolic enzymes isocitrate dehydrogenase 1/2 (IDH1/2) confer a novel gain-of-function in cancer cells, which results in the accumulation and secretion of the onco-metabolite, R-2-hydroxyglutarate (2-HG). High levels of 2-HG have been shown to inhibit αKG dependent dioxygenases including histone and DNA demethylases, which regulate the epigenetic state of cells and result in altered cellular differentiation. IDH1/2 mutations have been identified in a spectrum of both solid tumors and hematologic malignancies. This first clinical study explores the safety and clinical activity in advanced hematologic malignancies of AG-120 and AG-221, the first IDH mutant inhibitors in clinical trials. AG-120 and AG-221 are oral, potent, reversible, and selective inhibitors of the mutated IDH1 or 2 proteins, respectively. Data from the ongoing dose escalation, first in human phase 1 studies of AG-120 and AG-221 in patients with advanced IDH1/2 mutant positive hematologic malignancies are reported here. These phase I studies of oral AG-120 and AG-221 are designed to evaluate the safety, pharmacokinetics (PK), pharmacodynamics (PD) including assessment of 2-HG levels, and clinical activity in patients with advanced hematologic malignancies. AG-120 and AG-221 are administered orally 1 (QD) or 2 times per day (BID) in continuous 28-day cycles. Sequential cohorts of patients are enrolled at higher dose levels, followed by multiple planned expansion cohorts. The eligible patient population includes those with relapsed or refractory AML, myelodysplastic syndromes (MDS,) and elderly untreated AML that harbor an IDH2 mutation. Blood and bone marrow is collected at multiple time points for determination of the PK and PD effects of AG-221. Response assessments via bone marrow examination are performed on Days 15, 29, 57, and every 56 days (2 cycles) thereafter. Clinical Trial Information: NCT01915498

Transcatheter aortic valve replacement: US experience.

Aortic stenosis is the most frequent valvular heart disease in the USA, and aortic valve replacement remains the only definitive treatment. For patients who cannot have surgery or who are at an increased risk for surgical aortic valve replacement (SAVR), transcatheter aortic valve replacement (TAVR) has become an established treatment option. New technological developments in valve design will make TAVR available to an even wider group of patients. This review describes the TAVR procedure and its critical stages. To ensure that patients with aortic stenosis receive the best treatment option for them, evaluation by a multispecialty heart team is essential. In addition to determining TAVR vs. SAVR, the 'heart team' approach should be used for determining the access site, type, and size of valve, imaging modalities, and the type of anesthetic used for the procedure. Ability to perform TAVR in the cath lab under local anesthesia shortens the duration and lowers the cost of the procedure, and makes it even more attractive. TAVR is a treatment option for patients who are at an increased risk for SAVR. Evolving technology will likely expand the patient population eligible for this type of treatment in the very near future. Multidisciplinary heart team is essential in improving current techniques and patient selection, as well as evaluating new technologies.

PCN41 - Budget Impact Analysis of Aflibercept in yhe Treatment of Metastatic Colorectal Cancer (MCRC) in Poland

To estimate the budget impact resulting from the introduction of aflibercept for the treatment of metastatic colorectal cancer (mCRC) within drug program in Poland. Analysis was performed in 3-year time horizon (2014-2016) from the public payer (NHF) perspective. Target population is defined as adult patients with mCRC that is resistant to or has progressed after an oxaliplatin-containing regimen (including patients who experienced distant relapse within 6 months of completion of oxaliplatin-based adjuvant therapy). Eligible patient population was estimated by compilation of following data: epidemiological studies, local market study, IMS data, survey among Polish oncologists. Market shares of different regimens (aflibercept 4 mg/kg +FOLFIRI, bevacizumab 10 mg/kg +FOLFOX-4, FOLFIRI) were projected based on the NHF data and experts’ opinion. Following cost categories were included: drug acquisition and administration (anti-VEGF, chemotherapy), diagnostics, monitoring and adverse events (grade 3-4). With the introduction of aflibercept, estimated annual number of patients starting aflibercept treatment will be 90,209 and 224 in year 2014,2015 and 2016, respectively. Total annual expenditures in year 2014,2015 and 2016 were calculated to be 39.3, 40.3 and 41.2 million PLN in scenario without aflibercept, compared with 37.4, 34.9 and 35.0 million PLN, respectively, with the introduction of aflibercept. In case of aflibercept reimbursement, the NHF would save 1.9 million PLN in year 2014,5. 3 million PLN in year 2015 and 6.1 million PLN in year 2016. The introduction of aflibercept would result in savings for the NHF in Poland, mainly as a consequence of reduced pharmacological costs compared to bevacizumab.

Abstract CT103: Clinical safety and activity in a phase I trial of AG-221, a first in class, potent inhibitor of the IDH2-mutant protein, in patients with IDH2 mutant positive advanced hematologic malignancies

Abstract CT103: Clinical safety and activity in a phase I trial of AG-221, a first in class, potent inhibitor of the IDH2-mutant protein, in patients with IDH2 mutant positive advanced hematologic malignancies

Systematic Review and Comparison of Clinical Evidence Presented for Orphan Designated Treatments with European Medicines Agency Market Authorisation

ABSTRACT Aim: Conducting large, well-designed clinical trials for treatments indicated for orphan diseases presents certain challenges, including the low prevalence of such diseases. This study assessed the pivotal clinical evidence package presented in the European public assessment report for orphan-designated treatments with a European Medicines Agency (EMA) marketing authorisation. The evidence packages were compared in terms of the size of patient population in relation to the prevalence of the indicated orphan disease. Methods: All treatments reviewed in this study are assigned to anatomical therapeutic chemical (ATC) category ‘L’. This category was focused on because it is the largest ATC category (contains almost 50% of orphan-designated products) and includes all EMA-approved orphan oncology treatments. All treatments reviewed have been approved within the past 6 years and have been evaluated in a controlled trial using at least one survival-based clinical endpoint. Treatments were compared in terms of patient years (accumulated amount of time that patients are followed up), number of patients in the pivotal trial(s), and disease prevalence (information from Committee for Orphan Medicinal Products public summary of opinion). Results: Fourteen treatments fulfilled the inclusion criteria. Mifamurtide (Mepact®) was an outlier with 4,068 patient years; excluding mifamurtide, patient years ranged from 308 to 2,906 years (median 1,796 years). Mifamurtide was also found to have the second smallest eligible patient population (0.5/10,000 persons). The number of patients in the pivotal trial(s) ranged from 162 to 846 patients (median 485 patients); there were 678 patients in the mifamurtide pivotal trial. Conclusions: The low prevalence of orphan diseases often results in trials with low patient numbers and low patient years. The pivotal evidence package for mifamurtide (indicated for the orphan disease osteosarcoma) has both a small eligible patient population and the largest number of patient years. This study provides support for the robustness of the pivotal evidence package for mifamurtide. Disclosure: J.M. Winstone, S. Chadda and S. Ralston: PHMR Associates has received funding from Takeda to conduct the research; P. Sajosi: Peter Sajosi is an employee of Takeda.

Bladder cancer: ESMO Practice Guidelines for diagnosis, treatment and follow-up

Bladder cancer: ESMO Practice Guidelines for diagnosis, treatment and follow-up

Length of red cell unit storage and risk for delirium after cardiac surgery.

The time that red cell units are stored before transfusion may be associated with postoperative complications, although the evidence is conflicting. However, the association between the length of red cell unit storage and postoperative delirium has not been explored. We hypothesized that the length of storage of transfused red cell units would be associated with delirium after cardiac surgery. We conducted a case-control study in which patients undergoing coronary artery bypass, valve, or ascending aorta surgery with cardiopulmonary bypass at Johns Hopkins from 2005 to 2011 were eligible for inclusion. Patients were excluded if they did not receive red cell units, received >4 red cell units during hospitalization, received any transfusion after the first postoperative day, or received red cell units that were not exclusively stored for ≤14 days or >14 days. Eighty-seven patients met transfusion-related inclusion criteria and developed postoperative delirium. Controls who did not develop delirium were selected from the same source population of eligible patients and were matched 1:1 based on age (± 5 years), 2- to 2.5-year band of date of surgery, and surgical procedure. For each patient, we calculated the average storage duration of all transfused red cell units. The primary outcome was odds of delirium in patients who were transfused red cell units with exclusive storage duration >14 days compared with that of ≤14 days. Secondary outcomes were odds of delirium with each increasing day of average red cell unit storage duration. We used conditional multivariable regression to test our hypotheses. In conditional multivariable analysis of 87 case-control pairs, there was no difference in the odds of patients developing delirium if they were transfused red cell units with an exclusive storage age >14 days compared with that ≤14 days (odds ratio [OR] 1.83; 95% confidence interval, 0.73-4.58, P = 0.20). Each additional day of average red cell unit storage beyond 14 days was associated with a 1.01- to 1.13-fold increase in the odds of postoperative delirium (OR, 1.07; P = 0.03). Each additional day of average storage beyond 21 days was associated with a 1.02- to 1.23-fold increase in the odds of postoperative delirium (OR, 1.12; P = 0.02). Transfusion of red cell units that have been stored for >14 days is not associated with increased odds of delirium. However, each additional day of storage >14 or 21 days may be associated with increased odds of postoperative delirium in patients undergoing cardiac surgery. More research is needed to further characterize the association between delirium and storage duration of transfused red cell units.

Targeted erlotinib for first-line treatment of advanced non-small cell lung cancer: a budget impact analysis

Objectives:A recent phase III trial showed that patients with advanced non-small cell lung cancer (NSCLC) whose tumors harbor specific EGFR mutations significantly benefit from first-line treatment with erlotinib compared to chemotherapy. This study sought to estimate the budget impact if coverage for EGFR testing and erlotinib as first-line therapy were provided in a hypothetical 500,000-member managed care plan.Methods:The budget impact model was developed from a US health plan perspective to evaluate administration of the EGFR test and treatment with erlotinib for EGFR-positive patients, compared to non-targeted treatment with chemotherapy. The eligible patient population was estimated from age-stratified SEER incidence data. Clinical data were derived from key randomized controlled trials. Costs related to drug, administration, and adverse events were included. Sensitivity analyses were conducted to assess uncertainty.Results:In a plan of 500,000 members, it was estimated there would be 91 newly diagnosed advanced NSCLC patients annually; 11 are expected to be EGFR-positive. Based on the testing and treatment assumptions, it was estimated that 3 patients in Scenario 1 and 6 patients in Scenario 2 receive erlotinib. Overall health plan expenditures would increase by $0.013 per member per month (PMPM). This increase is largely attributable to erlotinib drug costs, in part due to lengthened progression-free survival and treatment periods experienced in erlotinib-treated patients. EGFR testing contributes slightly, whereas adverse event costs mitigate the budget impact. The budget impact did not exceed $0.019 PMPM in sensitivity analyses.Conclusions:Coverage for targeted first-line erlotinib therapy in NSCLC likely results in a small budget impact for US health plans. The estimated impact may vary by plan, or if second-line or maintenance therapy, dose changes/interruptions, or impact on patients’ quality-of-life were included.

Two-year comprehensive medical management of degenerative lumbar spine disease (lumbar spondylolisthesis, stenosis, or disc herniation): a value analysis of cost, pain, disability, and quality of life: clinical article.

Current health care reform calls for a reduction of procedures and treatments that are less effective, more costly, and of little value (high cost/low quality). The authors assessed the 2-year cost and effectiveness of comprehensive medical management for lumbar spondylolisthesis, stenosis, and herniation by utilizing a prospective single-center multidisciplinary spine center registry in a real-world practice setting. Analysis was performed on a prospective longitudinal quality of life spine registry. Patients with lumbar spondylolisthesis (n = 50), stenosis (n = 50), and disc herniation (n = 50) who had symptoms persisting after 6 weeks of medical management and who were eligible for surgical treatment were entered into a prospective registry after deciding on nonsurgical treatment. In all cases, comprehensive medical management included spinal steroid injections, physical therapy, muscle relaxants, antiinflammatory medication, and narcotic oral agents. Two-year patient-reported outcomes, back-related medical resource utilization, and occupational work-day losses were prospectively collected and used to calculate Medicare fee-based direct and indirect costs from the payer and societal perspectives. The maximum health gain associated with medical management was defined as the improvement in pain, disability, and quality of life experienced after 2 years of medical treatment or at the time a patient decided to cross over to surgery. The maximum health gain in back pain, leg pain, disability, quality of life, depression, and general health state did not achieve statistical significance by 2 years of medical management, except for pain and disability in patients with disc herniation and back pain in patients with lumbar stenosis. Eighteen patients (36%) with spondylolisthesis, 11 (22%) with stenosis, and 17 (34%) with disc herniation eventually required surgical management due to lack of improvement. The 2-year improvement did not achieve a minimum clinically important difference in any outcome measure. The mean 2-year total cost (direct plus indirect) of medical management was $6606 for spondylolisthesis, $7747 for stenosis, and $7097 for herniation. In an institution-wide, prospective, longitudinal quality of life registry that measures cost and effectiveness of all spine care provided, comprehensive medical management did not result in sustained improvement in pain, disability, or quality of life for patients with surgically eligible degenerative lumbar spondylolisthesis, stenosis, or disc herniation. From both the societal and payer perspective, continued medical management of patients with these lumbar pathologies in whom 6 weeks of conservative therapy failed was of minimal value given its lack of health utility and effectiveness and its health care costs. The findings from this real-world practice setting may more accurately reflect the true value and effectiveness of nonoperative care in surgically eligible patient populations.

Linking the Congenital Heart Surgery Databases of the Society of Thoracic Surgeons and the Congenital Heart Surgeons’ Society

A link has been created between the Society of Thoracic Surgeons Congenital Heart Surgery Database (STS-CHSD) and the Congenital Heart Surgeons' Society Database (CHSS-D). Five matrices have been created that facilitate the automated identification of patients who are potentially eligible for the five active CHSS studies using the STS-CHSD. These matrices are now used to (1) estimate the denominator of patients eligible for CHSS studies and (2) compare "eligible and enrolled patients" to "potentially eligible and not enrolled patients" to assess the generalizability of CHSS studies. The matrices were applied to 40 consenting institutions that participate in both the STS-CHSD and the CHSS to (1) estimate the denominator of patients that are potentially eligible for CHSS studies, (2) estimate the completeness of enrollment of patients eligible for CHSS studies among all CHSS sites, (3) estimate the completeness of enrollment of patients eligible for CHSS studies among those CHSS institutions participating in each CHSS cohort study, and (4) compare "eligible and enrolled patients" to "potentially eligible and not enrolled patients" to assess the generalizability of CHSS studies. The matrices were applied to all participants in the STS-CHSD to identify patients who underwent frequently performed operations and compare "eligible and enrolled patients" to "potentially eligible and not enrolled patients" in following five domains: (1) age at surgery, (2) gender, (3) race, (4) discharge mortality, and (5) postoperative length of stay. Completeness of enrollment was defined as the number of actually enrolled patients divided by the number of patients identified as being potentially eligible for enrollment. For the CHSS Critical Left Ventricular Outflow Tract Study (LVOTO) study, for the Norwood procedure, completeness of enrollment at centers actively participating in the LVOTO study was 34%. For the Norwood operation, discharge mortality was 15% among 227 enrolled patients and 16% among 1768 nonenrolled potentially eligible patients from the 40 consenting institutions. Median postoperative length of stay was 31 days and 26 days for these enrolled and nonenrolled patients. For the CHSS anomalous aortic origin of a coronary artery (AAOCA) study, for AAOCA repair, completeness of enrollment at centers actively participating in the AAOCA study was 40%. Determination of the denominator of patients eligible for CHSS studies and comparison of "eligible and enrolled patients" to "potentially eligible and not enrolled patients" provides an estimate of the extent to which patients in CHSS studies are representative of the overall population of eligible patients; however, opportunities exist to improve enrollment.