Approach For Real-world Data Research Articles

Comparing complication rates between Abbott Tendril 2088 and competitive manufacturer leads: Novel real-world data approach.

While several studies have reported on the reliability of cardiac pacing leads, there are limited comparative data on lead performance. We compared long-term performance of Abbott Tendril™ STS 2088TC (Tendril 2088) leads with competitive manufacturer (CM) pacing leads using novel real-world data analytic methods. Medicare fee-for-service (FFS) claims and Abbott device registration databases were linked to identify patients implanted with single-chamber or dual-chamber pacemakers with the Abbott Tendril 2088 lead from January 1, 2014 to December 31, 2019 and were followed through December 31, 2021. Medicare pacemaker patients who did not link to Abbott devices were assumed to have CM leads. Patients in both groups had to be enrolled in Medicare FFS at least 1 year before implant date and have an initial pacemaker and associated lead(s) implanted on the same date. Lead complications were identified based on a diagnosis code for a mechanical lead complication and a procedure code for a lead-related surgery on the same claim. Kaplan-Meier curves for lead intervention-free survival rates for up to 7 years of follow-up were compared between groups at the device level using a log-rank test. The study cohort had 89 629 Tendril 2088 and 433 481 CM lead patients. Groups were comparable in age (79.7 ± 8.6 years), sex (52.2% male), race/ethnicity, and baseline comorbidities. At 7 years, there was no significant difference in intervention-free survival rates between groups (97.48% Tendril 2088 vs. 97.52% CM, p = .3435). In this large Medicare population, there was no significant difference in lead complication rates between Tendril 2088 and CM pacing leads over 7 years of follow-up.

Effects of rifampin coadministration on the pharmacokinetics of digoxin: a real-world data approach.

Digoxin, a cardiac glycoside, is commonly prescribed to treat heart failure and atrial fibrillation. Because digoxin acts as a substrate of P-glycoprotein (P-gp), its blood concentration may be reduced by P-gp inducers such as rifampin. To assess the real-world implications of this drug-drug interaction, a retrospective analysis was carried out on the Clinical Data Warehouse at Seoul National University Hospital between 2012 and 2017. Eleven patients who received both digoxin and rifampin with satisfying the inclusion/exclusion criteria were identified. The Ctrough values of digoxin monotherapy were compared to those of the combination therapy with rifampin. Results demonstrated that the systemic exposure of orally administered digoxin decreased by 40% with the concurrent use of rifampin. Clinicians should be aware of potential drug interactions between digoxin and rifampin, as adjustments to digoxin dosage might be necessary for patients receiving rifampin or other P-gp inducer drugs.

Alpelisib (ALP), a breast cancer therapy, for PIK3CA-related overgrowth spectrum (PROS): A real-world data approach to a rare disease indication.

e18694 Background: PIK3CA mutations seen in cancer also drive other disease, exciting interest in repurposing oncology therapies for non-oncology indications. ALP is a PI3Kα inhibitor approved for HR+, HER2– ABC with fulvestrant. Clinical benefit of ALP in PROS, a group of rare phenotypically varied disorders driven by mutations in PIK3CA, was found in 19 pts (Venot, 2018). EPIK-P1 (NCT04285723) collected real-world data (RWD) to confirm ALP’s efficacy and safety in PROS. In the primary analysis of the primary endpoint, 12/32 pts (37.5%; 95% CI, 21.1-56.3%) with complete cases responded (≥20% reduction in the sum of target lesion volume from index/treatment [tx] start). Adverse events (AEs) and tx-related AEs were experienced by 82.5% (n = 47) and 38.6% (n = 22) of pts, respectively. The most common tx-related AE was hyperglycemia (n = 7, 12.3%). No deaths were reported (Canaud, ESMO 2021 LBA23). Methods: EPIK-P1 retrospectively abstracted data from the medical charts of pts aged ≥2 y with PROS experiencing severe/life-threatening conditions receiving ALP under compassionate use. Secondary endpoints evaluated safety and clinical benefit. Results: 57 pts were enrolled and followed for a median of 18.1 mo. No pt in the primary analysis (complete cases, n = 32) had progressive disease (PD) at wk 24; 1 pt discontinued ALP prior to wk 24 and considered a nonresponder. Of the 12 responders, median duration of response (time from first documented response to first documented PD or death due to any cause) was not estimable. Median time to censoring (date of last adequate lesion assessment) was 63.3 wk (̃14.6 mo; range, 1 d-186.7 wk); 2 pts had no further imaging assessments, 10 pts did not experience an event and tx was ongoing at data cutoff. Time to censoring was > 6 mo in 7 pts and > 12 mo in 6 pts. 11/20 nonresponders (55.0%) had target lesion volume reduction ranging from 0.7 to 19.6%. No pt required rescue surgery between index and wk 24. At index all pts reported ≥1 PROS-related symptom (eg, fatigue, pain). At wk 24, 82.5% (n = 47) reported symptom improvement regardless of primary analysis response status (responders, 10/12, 83.3%; nonresponders, 16/20, 80.0%). Median daily dose was 50 mg for pediatrics and 250 mg for adults. Dose reductions or interruptions were experienced by 15.8% of pts (n = 9); AEs led to dose reductions and interruptions in 3.5% (n = 2) and 10.5% (n = 6) of pts, respectively. 52 pts (91.2%) remained on tx at data cutoff; among 5 pts (8.8%) who discontinued, pt decision was the leading cause. Conclusions: RWD from EPIK-P1 demonstrate alpelisib as well tolerated, providing clinical benefit to pts with PROS regardless of response status in the primary analysis of the primary endpoint. Continued RWD collection complements planned prospective, randomized, placebo-controlled studies, facilitating access to alpelisib as an emerging pharmacologic option for PROS. Clinical trial information: NCT04285723.

National Cancer Information System Within the Framework of Health Insurance in Colombia: A Real-World Data Approach to Evaluate Access to Cancer Care.

PURPOSEThe National Cancer Information System (NCIS) has been operating since 2014, including information reported by health care insurers and providers on people with cancer diagnosed and treated within the Colombian health system. Its main purpose is to identify barriers to an effective access to cancer diagnosis and treatment across the country. We aimed to describe the methodology, scope and results in terms of access to health services with real-world data provided by the NCIS.METHODSReporting of all cases of cancer by insurers and providers is mandatory by law. Data gathered include demographic and clinical information about new and old cases of cancer who receive health services. Over the years, the reporting process has been automated and it is currently performed in real time. Data quality is ensured through a standardized data-monitoring process. Access to health services is monitored by quality measures defined by consensus.RESULTSSince 2015, prevalent cases of invasive cancer have increased from 163,776 to 331,021 in 2020 (increment of 102.12%). Regarding quality measures, the proportion of people staged at diagnosis has increased over the years, especially in breast cancer. Meanwhile, early diagnosis is still concerning for breast and prostate cancer. Time to diagnosis and treatment have not consistently reached the expected goals in breast, cervical, and prostate cancer, whereas they have shown a better level of compliance for stomach and colon and rectum tumors, still not reaching the highest performance.CONCLUSIONThe real-world information approach provided by the NCIS may be complementary for cancer control planning in Colombia, emphasizing better management processes of health insurers and providers by identifying barriers for timely access to health care.

Burden and magnitude of risk in HIV/AIDS in the Colombian health system: a real-world data approach. SUPPLEMENTARY MATERIAL

Burden and magnitude of risk in HIV/AIDS in the Colombian health system: a real-world data approach SUPPLEMENTARY MATERIAL

Burden and magnitude of risk in HIV/AIDS in the Colombian health system: a real-world data approach

Aim: To assess the epidemiological situation of people living with HIV and AIDS (PLWHA) in the municipalities and regions of Colombia in 2018. Materials and methods: A cross-sectional study was conducted with secondary data from the High-Cost Diseases Fund from February 1st, 2018 to January 31st, 2019. We included sociodemographic, clinical variables, and related to geographic location. We calculated incidence, prevalence, and mortality according to the Colombian geographical regions, department and municipality of residence. Crude and age-standardized rates were estimated. Results: By 2018, 10,930 new cases of PLWHA were reported, being more frequent in males, aged between 25 to 49 years. 39.32% were reported with AIDS and 35.27% had undetectable HIV viral load. During 2018, there are 109,056 PLWHA in Colombia. The highest age-standardized incidence and prevalence were reported in Florencia (Cauca) (354.28 per 100,000 and 3.32 per 100people, respectively). The age-standardized incidence rate was 22.12 per 100,000 population (95% CI 21.71- 22.54). Age-standardized prevalence and mortality were 0.23 per 100 population (95% CI 0.22-0.23) and 3.78 per 100,000 population (95% CI 3.61-3.96), respectively. Conclusion: Different strategies should be implemented to improve the identification of risk factors in the population, especially in some regions of Colombia and prevent transmission.

A real-world data approach to determine the optimal dosing strategy for pembrolizumab.

Cancer drug therapy costs continue to rise and threaten the sustainability of Canada's public healthcare system. Previous studies have calculated potential savings utilizing different dosing regimens of cancer treatments. Our objectives were to determine the financial impact of drug wastage and to explore cost-effective dosing regimens for pembrolizumab. This was a retrospective study reviewing data for non-small cell lung cancer and melanoma patients at all six BC Cancer Regional Centres during fiscal years 2017 and 2018. Pembrolizumab waste amounts recorded in pharmacy wastage logs were totalled. Estimates of the number of vials used were compared between vial sharing and non-vial sharing practices to determine the cost differences. Costs for dosing regimens used during fiscal years 2017 and 2018 were compared to 2 mg/kg weight-based dosing (to a maximum of 200 mg), 2 mg/kg dosing rounding down within 5% and 10%, and flat dosing of 200 mg. There were a total of 202 non-small cell lung cancer and 182 melanoma patients with 2948 doses dispensed. Documented wastage was valued at $1,829,047.44 (8.65%) and across all six centres, vial sharing could reduce costs by $3,207,600.00 using the 100 mg vials. Compared to fiscal years 2017 and 2018, 2 mg/kg dosing (to a maximum of 200 mg) was the most cost-effective, decreasing costs by $222,719.20; flat dosing of 200 mg was the most expensive, increasing costs by $6,625,260.40. Having smaller vial sizes, practicing vial sharing, and using weight-based dosing all improve cost savings. Further investigations on the allocation of resources to optimize drug use and minimize wastage are needed.

Use of a real-world data approach to rapidly generate outcomes data following a case study of a novel treatment combination in pancreatic adenocarcinoma.

e16735 Background: We use a real-world data approach to report on safety and benefits on metastatic pancreatic cancer pts who were treated with a MEK inhibitor plus hydroxychloroquine (HCQ) after exhausting all other treatment options. MEK inhibition acts on the KRAS pathway, which in turn increases autophagy as a resistance mechanism, furthermore, HCQ inhibits autophagy causing a cytotoxic effect. This combination was shown to diminish tumor volume in xenograft mouse models and a partial response in one heavily pre-treated patients was reported. Methods: XCELSIOR is an IRB approved, patient-centric, real-world data and outcomes registry for developing operational and analytic methods in precision oncology. Searching the XCELSIOR database, we identified 14 pts for whom this regimen had been considered. As part of their participation in XCELSIOR, these patients shared access to their full medical records, which were collected, processed, and abstracted into a 21 CFR 11 compliant database for analysis. We additionally collected de-identified data on 12 pts treated with this combination from five academic centers. Three more patients are expected to start treatment soon. Results: Between March 2018 and January 2020, 15 patients treated with the trametinib/HCQ combination and 3 patients treated with cobimetinib/HCQ were identified in XCELSIOR and five academic institutions. The median age at diagnosis was 64 (range 43-74) and 56% were male. For patients treated with trametinib/HCQ, the median time on treatment was 67 days (range 5-172 days), 11 patients were treated for more than 30 days (median time 97 days). The median PFS for this group was 2.9 months and the median OS was 7.4 months. The clinical benefit rate was 60% for the 10 evaluable patients treated with trametinib/HCQ, 1 patient had a partial response (previously published), 5 had stable disease (for at least 8 weeks) and 4 had progressive disease (physician reported). 2/3 patients treated with cobimetinib/HCQ were on treatment for more than 30 days and all three had progressive disease within 7 weeks. The most common side effects were Grade 1 fatigue and Grade 1/2 rash for both combinations. An additional 3 patients will start treatment soon and will be included in the analysis. Conclusions: Combinatorial MEK and autophagy inhibition was well tolerated in heavily treated metastatic pancreatic cancer patients. Trametinib/HCQ demonstrates some clinical benefit for this group. We demonstrate the feasibility of utilizing real-world data in precision oncology. Clinical trial information: NCT03793088 .

Cost-effectiveness of an adherence-enhancing intervention for gout based on real-world data.

AimMedication non‐adherence influences outcomes of therapies for chronic diseases. Allopurinol is a cornerstone therapy for patients with gout; however, non‐adherence to allopurinol is prevalent in Singapore and limits its effectiveness. Between 2008‐2010, an adherence‐enhancing program was implemented at the rheumatology division of a public tertiary hospital. The cost‐effectiveness of this program has not been fully evaluated. With healthcare resources being finite, the value of investing in adherence‐enhancing interventions should be ascertained. This study aims to evaluate the cost‐effectiveness of this adherence‐enhancing program to inform optimal resource allocation toward better gout management.MethodAdopting a real‐world data approach, we utilized patient clinical and financial records generated in their course of routine care. Intervention and control groups were identified in a standing database and matched on nine risk factors through propensity score matching. Cost and effect data were followed through 1‐2 years. A decision tree was developed in TreeAge using a societal perspective. Deterministic and probabilistic sensitivity analyses were performed to assess parameter uncertainty.ResultsAt an assumed willingness‐to‐pay threshold of $50 000 USD ($70 000 SGD) per quality‐adjusted life year (QALY), the intervention had an 85% probability of being cost‐effective compared to routine care. The incremental cost‐effectiveness ratio was $12 866 USD per QALY for the base case and ranged from $4 139 to $21 593 USD per QALY in sensitivity analyses.ConclusionThe intervention is cost‐effective in the short‐term, although its long‐term cost‐effectiveness remains to be evaluated.

CE2 - Cost-Effectiveness of An Adherence-Enhancing Intervention for Patients with Gout Based on Real-World Data

Medication non-adherence influences outcomes of therapies for chronic diseases. Allopurinol is a cornerstone therapy for patients with gout, however, non-adherence to allopurinol is prevalent in Singapore and limits its effectiveness. Between 2008–2010, an adherence-enhancing programme including health education, patient empowerment, and self-management training was implemented at the rheumatology division of a public tertiary hospital. The cost-effectiveness of this intervention has not been fully evaluated. As healthcare resources are finite, the value of investing in adherence-enhancing interventions should be ascertained. This study aims to evaluate the cost-effectiveness of this adherence-enhancing programme so as to inform optimal resource allocation toward better gout management. Adopting a real-world data approach, we utilized patient clinical, pharmacy, and financial records generated in their course of routine hospital care. 111 intervention and 198 control patients were identified in a standing database and matched on nine risk factors through propensity score matching. Cost and utility data were followed through one to two years for 106 matched results. A decision tree was developed with TreeAge Software using a societal perspective. Deterministic and probabilistic sensitivity analyses were performed to assess parameter uncertainty. At an assumed willingness-to-pay threshold of 70,000 SGD (equivalent to 50,000 USD) per quality-adjusted life year (QALY), the intervention had an 85% probability of being cost-effective compared to routine care. The incremental cost-effectiveness ratio (ICER) was 18,121 SGD per QALY for the base case and ranged from 5,829 to 30,413 SGD per QALY in sensitivity analyses. The model driver is inpatient cost which was the least robust based on Tornado analysis. The intervention is cost-effective in the short-term, although its long-term cost-effectiveness remains to be evaluated.

Population Impact of Drug Interactions with Warfarin: A Real-World Data Approach.

To investigate the population impact of previously reported interactions between warfarin and other drugs on international normalized ratio (INR) levels. Using The Health Improvement Network (THIN), a United Kingdom primary care database, a cohort of warfarin users between 2005 and 2013 (N = 121,962) was followed until the first qualifying prescription for the potential interacting drugs was evaluated. Sixteen sub-cohorts, one for each study drug, and a control sub-cohort of warfarin were ascertained. Short-term changes in INR levels were assessed by comparing INR values measured before and after initiation of the interacting drug with paired Student's t-test. We also evaluated the proportion of patients with INR values outside the therapeutic range (INR: 2-3). Miconazole use was associated with the highest mean increase in INR (+3.35), followed by amiodarone (+1.28), fluconazole (+0.79), metronidazole (+0.75) and nystatin (+0.65). After subtracting the natural INR variation observed in the control sub-cohort, supra-therapeutic levels (INR > 3) were found in 53.2% (miconazole), 45.5% (amiodarone), 23.3% (metronidazole), 23.2% (fluconazole) and 17.6% (nystatin) of patients initiating treatment with these drugs. Carbamazepine use was associated with a mean INR decrease of -0.63 and infra-therapeutic levels (INR < 2) were observed in 46.2% of patients initiating carbamazepine. For all other drugs, the change was small to moderate, in absolute INR units (+0.23 to +0.55) and in the proportion of patients with INR levels out of therapeutic range (<16%). Clinically potentially important interactions were observed in several study drugs. The majority of them, although confirmed, had little impact after adjusting for standard INR variability in the general population of warfarin users.

Efficient Bayesian Inference for Multivariate Factor Stochastic Volatility Models

ABSTRACTWe discuss efficient Bayesian estimation of dynamic covariance matrices in multivariate time series through a factor stochastic volatility model. In particular, we propose two interweaving strategies to substantially accelerate convergence and mixing of standard MCMC approaches. Similar to marginal data augmentation techniques, the proposed acceleration procedures exploit nonidentifiability issues which frequently arise in factor models. Our new interweaving strategies are easy to implement and come at almost no extra computational cost; nevertheless, they can boost estimation efficiency by several orders of magnitude as is shown in extensive simulation studies. To conclude, the application of our algorithm to a 26-dimensional exchange rate dataset illustrates the superior performance of the new approach for real-world data. Supplementary materials for this article are available online.

Designing and incorporating a real world data approach to international drug development and use: what the UK offers

Assessments of the safety, efficacy and appropriate use of new medicines lie at the heart of treatment development and subsequent adoption in clinical practice. Highly controlled randomised clinical trials routinely inform decisions on the approval, coverage and use of a medicine. Researchers and decision makers have become increasingly aware that these experimental data alone are insufficient to address those decisions fully. Real world data recorded from routine healthcare delivery by healthcare professionals and patients help provide a more complete picture of care. The UK, with its connectivity and rich longitudinal patient records, accumulated research and informatics experience and National Health Service, provides an exemplar of how real world data address a wide range of challenges across drug development.

An approach for real world data modelling with the 3D terrestrial laser scanner for built environment

Capturing and modelling 3D information of the built environment is a big challenge. A number of techniques and technologies are now in use. These include EDM, GPS, and photogrammetric application and also remote sensing applications. In this paper, we discussed 3D laser scanning technology, which can acquire high density point data in an accurate, fast way. Besides, the scanner can digitize all the 3D information concerned with a real world object such as buildings, trees and terrain down to millimetre detail Therefore, it can provide benefits for refurbishment process in regeneration in the Built Environment. A series of scans externally and internally allows an accurate 3D model of the building to be produced. This model can be sliced through different planes to produce accurate 2D plans and elevations. This novel technology improves the efficiency and quality of construction projects such as maintenance of buildings or group of building that are going to be renovated for new services in the Built Environment. In addition, the laser scanner technology can be used in integration with differential GPS for terrain modelling for the analysis and inspection of terrain structure accurately. In this paper, two case studies are introduced to demonstrate the use of laser scanner technology in Built Environment. These case studies are the Jactin House Building in East Manchester and the Peel building in the campus of University Salford. Through these case studies, while use of laser scanners are explained, the integration of it with various technologies and systems are also explored for professionals in both Built and Natural Environment.