Linkage of the CF foundation patient registry with the pediatric health information system database.

INTRODUCTION: The Cystic Fibrosis Foundation Patient Registry (CFFPR) contains clinical and demographic data from ∼85% of US cystic fibrosis (CF) patients across 120 care centers, but lacks robust inpatient hospitalization data. In contrast, the Pediatric Health Information System (PHIS) database includes inpatient clinical and resource utilization data from 49 US children's hospitals. The creation of a linked CFFPR-PHIS dataset can uniquely address questions related to in-hospital pediatric CF treatment and management. We assessed the feasibility of linking the CFFPR and PHIS databases and determined if successfully linked CF patients were generalizable to unlinked patients. METHODS: CF patients ≤21 years were eligible for linkage. The CFFPR and PHIS databases were linked at the patient level using indirect identifiers in a stepwise, deterministic, linkage approach. A validation cohort was created using a subset of patients to determine linkage accuracy. Clinical and demographic characteristics between linked and unlinked patients were compared to determine generalizability of the linked cohort. RESULTS: Of the 11 735 CF patients eligible for linkage from January 1st, 2005 through December 31st, 2016, 10 660 (91%) were successfully linked. Results of our single center validation cohort illustrated 100% accuracy. When compared to unlinked CF patients, fewer linked patients were born before 1990, more were Hispanic, and more were from West-affiliated PHIS hospitals. Otherwise, no clinically meaningful differences were seen between linked and unlinked CF patients. CONCLUSIONS: We demonstrated successful linkage of the CFFPR and PHIS databases, and created a large generalizable pediatric CF cohort for use in CF-related research.

Rate and predictors of prescription of lumacaftor - Ivacaftor in the 18 months following approval in the United States.

RATIONALE: Lumacaftor-ivacaftor (LUM-IVA) was approved in the US in 2015 for patients with CF aged >12 homozygous for the delF508 mutation, and patients aged 6 to 12 in 2016. OBJECTIVES: To examine the rate of initial LUM-IVA prescriptions following approval. METHODS: We compared patients eligible for LUM-IVA in the CF Foundation Patient Registry with and without prescriptions in 2015-2016. RESULTS: 5534 (53%) eligible patients had reported prescriptions. Prescription rate in children ages 6-11 was 19% and 61% among patients ≥12 years old. Individuals ≥12 with prescriptions more likely observed among those with private insurance, clinical trial participation, ages 18-30, FEV1 < 90%, more pulmonary exacerbations, and more use of chronic medications. CONCLUSIONS: LUM-IVA uptake was less rapid than what was previously observed for ivacaftor, a CFTR modulator approved for a different population. Age, insurance status, disease severity and use of other therapies differed in those prescribed LUM-IVA in the initial post-approval period.

Precision Medicine In Action: The Impact Of Ivacaftor On Cystic Fibrosis-Related Hospitalizations.

Cystic fibrosis is a life-threatening genetic disease that causes severe damage to the lungs. Ivacaftor, the first drug that targeted the underlying defect of the disease caused by specific mutations, is a sterling example of the potential of precision medicine. Clinical trial and registry studies showed that ivacaftor improved outcomes and reduced hospitalizations. Our study used US administrative claims data to assess the real-world effectiveness of ivacaftor. Comparing twelve-month rates before and after starting the use of ivacaftor among people who initiated therapy during 2012-2015, we found that overall and cystic fibrosis-related inpatient admissions fell by 55 percent and 81 percent, respectively. There was a comparable reduction in inpatient spending. Ivacaftor appears to be effective for multiple mutations that cause the disease, as suggested by the fact that during the study period, ivacaftor's use was extended to nine additional mutations in 2014. Examination of evidence from clinical trial, clinical care, and administrative data sources is important for understanding the real-world effectiveness of precision medicines such as ivacaftor.

Cost Effectiveness of Screening Individuals With Cystic Fibrosis for Colorectal Cancer.

BACKGROUND & AIMS: Individuals with cystic fibrosis are at increased risk of colorectal cancer (CRC) compared with the general population, and risk is higher among those who received an organ transplant. We performed a cost-effectiveness analysis to determine optimal CRC screening strategies for patients with cystic fibrosis. METHODS: We adjusted the existing Microsimulation Screening Analysis-Colon model to reflect increased CRC risk and lower life expectancy in patients with cystic fibrosis. Modeling was performed separately for individuals who never received an organ transplant and patients who had received an organ transplant. We modeled 76 colonoscopy screening strategies that varied the age range and screening interval. The optimal screening strategy was determined based on a willingness to pay threshold of $100,000 per life-year gained. Sensitivity and supplementary analyses were performed, including fecal immunochemical test (FIT) as an alternative test, earlier ages of transplantation, and increased rates of colonoscopy complications, to assess if optimal screening strategies would change. RESULTS: Colonoscopy every 5 years, starting at an age of 40 years, was the optimal colonoscopy strategy for patients with cystic fibrosis who never received an organ transplant; this strategy prevented 79% of deaths from CRC. Among patients with cystic fibrosis who had received an organ transplant, optimal colonoscopy screening should start at an age of 30 or 35 years, depending on the patient's age at time of transplantation. Annual FIT screening was predicted to be cost-effective for patients with cystic fibrosis. However, the level of accuracy of the FIT in this population is not clear. CONCLUSIONS: Using a Microsimulation Screening Analysis-Colon model, we found screening of patients with cystic fibrosis for CRC to be cost effective. Because of the higher risk of CRC in these patients, screening should start at an earlier age with a shorter screening interval. The findings of this study (especially those on FIT screening) may be limited by restricted evidence available for patients with cystic fibrosis.

Cost-Effectiveness of Screening Individuals With Cystic Fibrosis for Colorectal Cancer.

BACKGROUND & AIMS: Individuals with cystic fibrosis are at increased risk of colorectal cancer (CRC) compared to the general population, and risk is higher among those who received an organ transplant. We performed a cost-effectiveness analysis to determine optimal CRC screening strategies for patients with cystic fibrosis. METHODS: We adjusted the existing Microsimulation Screening Analysis-Colon microsimulation model to reflect increased CRC risk and lower life expectancy in patients with cystic fibrosis. Modeling was performed separately for individuals who never received an organ transplant and patients who had received an organ transplant. We modeled 76 colonoscopy screening strategies that varied the age range and screening interval. The optimal screening strategy was determined based on a willingness to pay threshold of $100,000 per life-year gained. Sensitivity and supplementary analyses were performed, including fecal immunochemical test (FIT) as an alternative test, earlier ages of transplantation, and increased rates of colonoscopy complications, to assess whether optimal screening strategies would change. RESULTS: Colonoscopy every 5 years, starting at age 40 years, was the optimal colonoscopy strategy for patients with cystic fibrosis who never received an organ transplant; this strategy prevented 79% of deaths from CRC. Among patients with cystic fibrosis who had received an organ transplant, optimal colonoscopy screening should start at an age of 30 or 35 years, depending on the patient's age at time of transplantation. Annual FIT screening was predicted to be cost-effective for patients with cystic fibrosis. However, the level of accuracy of the FIT in population is not clear. CONCLUSIONS: Using a Microsimulation Screening Analysis-Colon microsimulation model, we found screening of patients with cystic fibrosis for CRC to be cost-effective. Due to the higher risk in these patients for CRC, screening should start at an earlier age with a shorter screening interval. The findings of this study (especially those on FIT screening) may be limited by restricted evidence available for patients with cystic fibrosis.

Survival Comparison of Patients With Cystic Fibrosis in Canada and the United States: A Population-Based Cohort Study.

BACKGROUND: In 2011, the median age of survival of patients with cystic fibrosis reported in the United States was 36.8 years, compared with 48.5 years in Canada. Direct comparison of survival estimates between national registries is challenging because of inherent differences in methodologies used, data processing techniques, and ascertainment bias. OBJECTIVE: To use a standardized approach to calculate cystic fibrosis survival estimates and to explore differences between Canada and the United States. DESIGN: Population-based study. SETTING: 42 Canadian cystic fibrosis clinics and 110 U.S. cystic fibrosis care centers. PATIENTS: Patients followed in the Canadian Cystic Fibrosis Registry (CCFR) and U.S. Cystic Fibrosis Foundation Patient Registry (CFFPR) between 1990 and 2013. MEASUREMENTS: Cox proportional hazards models were used to compare survival between patients followed in the CCFR (n = 5941) and those in the CFFPR (n = 45 448). Multivariable models were used to adjust for factors known to be associated with survival. RESULTS: Median age of survival in patients with cystic fibrosis increased in both countries between 1990 and 2013; however, in 1995 and 2005, survival in Canada increased at a faster rate than in the United States (P < 0.001). On the basis of contemporary data from 2009 to 2013, the median age of survival in Canada was 10 years greater than in the United States (50.9 vs. 40.6 years, respectively). The adjusted risk for death was 34% lower in Canada than the United States (hazard ratio, 0.66 [95% CI, 0.54 to 0.81]). A greater proportion of patients in Canada received transplants (10.3% vs. 6.5%, respectively [standardized difference, 13.7]). Differences in survival between U.S. and Canadian patients varied according to U.S. patients' insurance status. LIMITATION: Ascertainment bias due to missing data or nonrandom loss to follow-up might affect the results. CONCLUSION: Differences in cystic fibrosis survival between Canada and the United States persisted after adjustment for risk factors associated with survival, except for private-insurance status among U.S. patients. Differential access to transplantation, increased posttransplant survival, and differences in health care systems may, in part, explain the Canadian survival advantage. PRIMARY FUNDING SOURCE: U.S. Cystic Fibrosis Foundation.

The Cystic Fibrosis Foundation Patient Registry. Design and Methods of a National Observational Disease Registry.

RATIONALE: The Cystic Fibrosis Foundation Patient Registry (CFFPR) is an ongoing patient registry study that collects longitudinal demographic, clinical, and treatment information about persons with cystic fibrosis (CF) in the United States. CF is a life-shortening genetic disorder that occurs in approximately 1 in 3,500 births in the United States. High-quality observational data is important for clinical research, quality improvement, and clinical management. OBJECTIVES: To describe the data collection, patient population, and key limitations of the CFFPR. METHODS: Inclusion criteria for the CFFPR include diagnosis with CF or a CFTR-associated disorder, care at an accredited care center program, and provision of informed consent. Data from clinic visits and hospitalizations are collected through a secure website. Loss to follow-up and generalizability were examined using several methods. The accuracy of CFFPR data was evaluated with an audit of 2012 CFFPR data compared to the medical record. MEASUREMENTS AND MAIN RESULTS: Since 1986, the CFFPR contains the records of 48,463 individuals with CF. Participation among individuals seen at accredited care centers is high, and loss to follow-up is low. An audit of 2012 CFFPR data suggests that the CFFPR contains 95% of clinic visits and 90% of hospitalizations found in the medical record for these patients, and nearly all of the audited fields were highly accurate. CONCLUSIONS: Registries such as the CFFPR are important tools for research, clinical care, and tracking incidence, mortality and population trends.