Real Word Evidence Research Articles

Health and economic impact of subcutaneous allergen immunotherapy in patients with pollen-induced allergic rhinoconjunctivitis: real-word evidence from the Czech Republic.

Background: The prevalence of allergic rhinoconjunctivitis (AR) has been increasing over the years, and allergen immunotherapy (AIT) remains the only disease-modifying treatment. However, cost-effectiveness data remain scarce. Methods: In this single-arm, noninterventional, prospective, multicenter study, we describe the effectiveness, safety and costs of subcutaneous AIT for pollen-induced allergic rhinoconjunctivitis. Results: Of 471 new AIT users, 317 completed three courses of treatment, and symptoms improved in 96%; no serious adverse reactions were reported. The cost of symptomatic medication decreased by 49% and the cost of unscheduled specialist visits decreased by 73%. Except for AIT administration, total healthcare costs decreased by 54% compared with the baseline pollen season without AIT. Conclusion: In clinical practice, subcutaneous AIT is an effective treatment generating savings on symptomatic medication and unscheduled consultations.

Health Canada Usage of Real World Evidence (RWE) in Regulatory Decision Making compared with FDA/EMA usage based on publicly available information.

Between January 2020 and December 2021, Health Canada provided a Summary Basis of Decision (SBD) for each of 110 products approved, including 29 oncology products and 21 non-oncology orphan drugs. This review sought to gain insight into how Real Word Evidence (RWE) impacts regulatory decision making. SBDs for oncology drugs and non-oncology orphan drugs were reviewed for evidence of use of the RWE or historical data to support regulatory decisions. This information was compared with both FDA and EMA reviews. For the 29 Health Canada-approved oncology products, 11 were approved with Notice of Compliance with Conditions (NOCc) status. Two NOCc approvals received extensive RWE reviews, while two other approvals briefly mentioned the use of RWE/historical data. Of the 12 NOC approvals, one received RWE reviews. FDA also approved all 29 drugs, 14 of which received extensive comments on RWE and/or historical data and 8 of which mentioned RWE or historical data. EMA approved 25 of the 29 products and provided extensive comments on 10. Four products received a mention of RWE review. The percentages of submissions with RWE/historical reviews conducted by Health Canada, FDA and EMA were 24.1, 75.9 and 56.0 respectively. Of the 21 non-oncology orphan drugs, Health Canada provided priority review status to 11, with extensive RWE comments in 5 and the mention of RWE in 2 of the regular approvals. Two approvals that used third-party data were not included in the comparison. FDA approved 19, and provided extensive RWE assessment on 5 and mentioned use of historical data in 8. EMA approved 17 and provided extensive RWE and historical comments in 7 and mentioned historical data in 4. The percentages of submissions with RWE/historical reviews by Health Canada, FDA and EMA were 36.8, 68.4 and 64.7 respectively. Use of Real World Data is common among FDA/EMA reviews and Health Canada used RWE in recent NOCc and orphan drug approvals.

Real-word evidence in patients treated with pazopanib for advanced/metastatic renal cell carcinoma (mRCC): The APOLON study.

299 Background: The efficacy and safety of pazopanib (PZP) have been evaluated in pivotal randomized, clinical trials Real-world evidence (RWE) is required to further assess its use, effectiveness and safety in mRCC in clinical routine practices. Methods: APOLON is a non-interventional, multicentric prospective study with mRCC patients who receive frontline PZP treatment. The study is designed to assess PZP Progression-Free Survival (PFS) (under treatment), Overall Survival (OS), Objective Response Rate (ORR) assessed by investigators, tolerability and subsequent post-pazopanib therapy sequences. Impact of COVID-19 on patient’s care was also assessed. Eligible patients were recruited from Nov 2017 to Jan 2019 in 55 participant sites in France. This interim analysis presents results 30 months (mo) after last patient was enrolled in the study. Results: The 217 patients were 71.1% males, with a median age of 69.6 years and had mRCC with a favourable (27.1%), intermediate (52.1%) or poor (20.8%) IMDC risk score according to physician. ECOG-PS was 0, 1 and ≥2 in respectively 43.3%, 39% and 17.6% of patients. Metastases were mainly located in lungs (64.1%), bones (28.6%), mediastinal (18%)/abdominal (17.1%). Patients had an history of partial/total nephrectomy in 54.8% of cases and previous local treatments for metastases in 27.6%. Median PFS, assessed by investigator, was 10.5 mo (95%CI: 9-12.4), similarly in patients < 65-year-old (YO) with 11.3 mo (95%CI: 7-16.3) and in those ≥ 65 YO with 9.9 mo (95%CI: 8.9-12). When assessed according to the IMDC risk score, mPFS was 18.1 mo (95%CI: 9.9-23.3) in favourable, 11.5 mo (95%CI: 8.7-14.4) in intermediate and 6.2 mo (95%CI: 3.5-9.5) in poor mRCC. The median OS was 27.3 mo (95%CI: 24.3 - ND). Investigator-assessed ORR was 48.3% with a CR in 6 patients (3.5%) and a PR in 77 (44.8%). After a median treatment duration of 10.1 mo, 190 patients (87.6%) discontinued PZP and 67.9% received at least one post-PZP line. Second line post-PZP consisted in nivolumab (71.3%), cabozantinib (14.7%), sunitinib (7%) or other (7%). Adverse Event (AE) leading to PZP dose reduction and discontinuation were reported in 42% and 40.9% of patients and treatment-related serious AE in 22.2% of patients. No safety signal was newly identified. The impact of the Covid 19 pandemic was limited on patients’ cares and study follow-up. Visits during the pandemic included 84.1% of tumour evaluation. For 29 patients (14.1%), follow-up visits were carried out as a teleconsultation. Few patients (5,7%) had no visits during the pandemic. Conclusions: The APOLON study confirms PZP effectiveness and safety in patients with mRCC in real-life setting. The efficacy of pazopanib remains significant in patients aged 65 years and older. It is highly associated with risk score. The COVID pandemics had limited impact on patients’ cares.

Characterizing Mild and Moderate Hemophilia A Patients in the Real World: A Patient-Centric Approach

Characterizing Mild and Moderate Hemophilia A Patients in the Real World: A Patient-Centric Approach

Standardizing registry data to the OMOP Common Data Model: experience from three pulmonary hypertension databases

BackgroundThe Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM) can be used to transform observational health data to a common format. CDM transformation allows for analysis across disparate databases for the generation of new, real-word evidence, which is especially important in rare disease where data are limited. Pulmonary hypertension (PH) is a progressive, life-threatening disease, with rare subgroups such as pulmonary arterial hypertension (PAH), for which generating real-world evidence is challenging. Our objective is to document the process and outcomes of transforming registry data in PH to the OMOP CDM, and highlight challenges and our potential solutions.MethodsThree observational studies were transformed from the Clinical Data Interchange Standards Consortium study data tabulation model (SDTM) to OMOP CDM format. OPUS was a prospective, multi-centre registry (2014–2020) and OrPHeUS was a retrospective, multi-centre chart review (2013–2017); both enrolled patients newly treated with macitentan in the US. EXPOSURE is a prospective, multi-centre cohort study (2017–ongoing) of patients newly treated with selexipag or any PAH-specific therapy in Europe and Canada. OMOP CDM version 5.3.1 with recent OMOP CDM vocabulary was used. Imputation rules were defined and applied for missing dates to avoid exclusion of data. Custom target concepts were introduced when existing concepts did not provide sufficient granularity.ResultsOf the 6622 patients in the three registry studies, records were mapped for 6457. Custom target concepts were introduced for PAH subgroups (by combining SNOMED concepts or creating custom concepts) and World Health Organization functional class. Per the OMOP CDM convention, records about the absence of an event, or the lack of information, were not mapped. Excluding these non-event records, 4% (OPUS), 2% (OrPHeUS) and 1% (EXPOSURE) of records were not mapped.ConclusionsSDTM data from three registries were transformed to the OMOP CDM with limited exclusion of data and deviation from the SDTM database content. Future researchers can apply our strategy and methods in different disease areas, with tailoring as necessary. Mapping registry data to the OMOP CDM facilitates more efficient collaborations between researchers and establishment of federated data networks, which is an unmet need in rare diseases.

26588 Patient-reported outcomes from a large, North American-based cohort, highlight a greater disease burden for generalized pustular psoriasis vs plaque psoriasis: Real-world evidence from the Corrona Psoriasis Registry

Generalized pustular psoriasis (GPP) is a rare, systemic disease characterized by recurrent flares of painful neutrophilic aseptic pustules. There is limited real-word evidence characterizing patients with GPP. Establishing the distinguishing characteristics of GPP relative to plaque psoriasis may help inform future treatment and improve patient outcomes. Adults with GPP (n = 60) or plaque psoriasis (n = 4894) identified from the North American-based Corrona Psoriasis Registry were included in descriptive analyses.

Prevalence of Avoidable and Bias-Inflicting Methodological Pitfalls in Real-World Studies of Medication Safety and Effectiveness.

Many real-word evidence (RWE) studies that utilize existing healthcare data to evaluate treatment effects incur substantial but avoidable bias from methodologically flawed study design; however, the extent of preventable methodological pitfalls in current RWE is unknown. To characterize the prevalence of avoidable methodological pitfalls with potential for bias in published claims-based studies of medication safety or effectiveness, we conducted an English-language search of PubMed for articles published from January 1, 2010 to May 20, 2019 and randomly selected 75 studies (10 case-control and 65 cohort studies) that evaluated safety or effectiveness of cardiovascular, diabetes, or osteoporosis medications using US health insurance claims. General and methodological study characteristics were extracted independently by two reviewers, and potential for bias was assessed across nine bias domains. Nearly all studies (95%) had at least one avoidable methodological issue known to incur bias, and 81% had potentially at least one of the four issues considered major due to their potential to undermine study validity: time-related bias (57%), potential for depletion of outcome-susceptible individuals (44%), inappropriate adjustment for postbaseline variables (41%), or potential for reverse causation (39%). The median number of major issues per study was 2 (interquartile range (IQR), 1-3) and was lower in cohort studies with a new-user, active-comparator design (median 1, IQR 0-1) than in cohort studies of prevalent users with a nonuser comparator (median 3, IQR 3-4). Recognizing and avoiding known methodological study design pitfalls could substantially improve the utility of RWE and confidence in its validity.

The real-word evidence of first-line treatment of pembrolizumab in advanced NSCLC.

e18731 Background: For advanced non-small cell lung cancer (NSCLC), evidence from clinical trials indicates the superiority of pembrolizumab (P) than chemotherapy (C) in PD-L1 positive patients and superiority of P+C than C among PD-L1 unselected patients. Meta-analysis from different clinical trials stated P+C failed to improve overall survival (OS) or progression-free survival (PFS) compared with P alone. This study used real-world data of PD-L1+ patients with advanced NSCLC to compare treatment effect of P with P+C. Methods: A retrospective analysis of adult patients diagnosed between 2015-2020 with stage IV NSCLC with PD-L1+ and without EGFR/ALK mutation was examined using de-identified Syapse Learning Health Network(LHN). We compared the patients with first-line (1L) treatment of pembrolizumab + carboplatin + chemo (P+C) and patients with 1L treatment of P only (P). Patient characteristics and survival outcomes including real-world OS (rwOS) and real-world time to next treatment (rwTTNT) were collected. Results: 485 patients were included: 231 on P+C and 254 on P. The two groups are similar in race, primary tumor histology and ECOG, and P are older in age and have more female. The median rwOS for P+C is longer than P (13.2 vs 11.0 month), 1 year survival probability is higher (55% vs 49%), but 2 year survival probability is lower (34% vs 39%). Coxph model shows no significant difference between two groups (HR=0.89, 95% CI 0.69-1.14, p=0.34). Subgroup analysis of patients age≥75 shows median rwOS for P+C is shorter than P (8.7 vs 13.2 month), 1 year survival probability is lower (46% vs 51%). Coxph model shows no significant difference between two groups (HR=1.32, 95% CI 0.81-2.16, p=0.27). In each treatment group, the median rwOS for female is longer than male (13.2 vs 7.9 month in P, 15.8 vs 12.2 month in P+C), and 1 year survival probability is higher (52% vs 45% in P, 59% vs 53% in P+C). Coxph model shows no significant difference between female and male (HR=0.81, 95% CI 0.58-1.15, p=0.23 in P; HR=0.90, 95% CI 0.62-1.30, p=0.57 in P+C). Conclusions: Among patients with PD-L1+ advanced NSCLC, there is no significant difference in rwOS for patients with 1L treatment of P+C or P alone.[Table: see text]

Advantages of Metformin Therapy for the Prevention and Mitigation of Diabetic Foot Ulcer in Patients With Diabetic Kidney Disease: A Real-Word Evidence From Large-Scale Cohort

Background: Diabetic foot ulcer (DFU) and diabetic kidney disease (DKD) are diabetes-related microvascular complications strongly correlated with high morbidity and mortality. While metformin potentially confers a wound-healing advantage, there is no well-established clinical evidence. This study investigates the effect of metformin on DFU from large DKD cohort for the first time. Methods: This retrospective cohort study enrolled DKD patients from two South Korean tertiary-referral centers between 2001 and 2016. Primary outcomes were all-cause mortality and DFU events; secondary outcomes included hospitalization, amputation, composite of amputation or vascular intervention, and Wagner Grade≥3. Multivariate cox analysis and propensity score matching (PSM) were used to balance baseline intergroup differences between metformin users and metformin non-users. Findings: Among 10,832 patients (4,748 metformin users; 6,084 metformin non-users), the 117·5±66·9 months follow-up period, all-cause mortality rate and DFU incidence were 37·1%, and 5·2%, respectively. Fully adjusted multivariate Cox analysis showed that metformin users had lower all-cause mortality (adjusted hazard ratio 0·63; 95% confidence interval 0·58–0·68; p<0·001) and DFU events (0·39; 0·31–0·48; p<0·001). After PSM, metformin users showed lower all-cause mortality (0·61; 0·55–0·67; p<0·001), DFU events (0·42; 0·32–0·56; p<0·001), and secondary outcomes. Interpretation: Metformin therapy in DKD patient can lower all-cause mortality, DFU incidence, and DFU progression. Funding Information: This work was partly supported by Institute of Information & Communications Technology Planning & Evaluation project funded by Korean government (Ministry of the Interior and Safety; no.2021-0-01177) and public clinical research grant-in-aid from Seoul Metropolitan Government-Seoul National University Boramae Medical Center (no.04-2021-0042). Declaration of Interests: All authors declare that they have no conflict of interest. Ethics Approval Statement: This study protocol was approved by the Institutional Review Board of SNUH (No. J-2010-119-1166) and BRMH (No. 30-2020-128). The requirement for informed consent was waived by the approving authority due to the study design. All clinical investigations were conducted in accordance with the principles of the Declaration of Helsinki and its 2013 amendment.

Real word evidence on rituximab utilization: Combining administrative and hospital-pharmacy data.

To describe patterns of utilization, survival and infectious events in patients treated with rituximab at the University Hospital of Siena (UHS) to explore the feasibility of combining routinely collected administrative and hospital-pharmacy data for examining the real-world use of intravenous antineoplastic drugs. A retrospective, longitudinal cohort study was conducted using data from the Hospital Pharmacy of Siena (HPS) and the Regional Administrative Database of Tuscany (RAD). Patients aged ≥18 years with ≥1 rituximab administration recorded between January 2012 and June 2016 were identified in the HPS database. Anonymized patient-level data were linked to RAD. Rituximab utilization during the first year of treatment was described using HPS. Hospital diagnoses of adverse infectious events that occurred during the first year of follow-up and four-year survival were observed using RAD. A total of 311 new users of rituximab were identified: 264 patients received rituximab for non-Hodgkin's lymphoma (NHL) and 47 were treated for chronic lymphocytic leukemia (CLL). Among new users with one complete year of follow-up (n = 203) over 95% received rituximab as the first-line treatment, and approximately 70% of them received 5-8 doses. No patient in the CLL group received >8 administrations. Four-year survival was approximately 70% in both CLL and NHL patients. Sepsis was the most frequent infectious event observed (5.1%). HPS and RAD provided complementary information on rituximab utilization, demonstrating their potential for future pharmacoepidemiological studies on antineoplastic medications administered in the Italian hospital setting. Overall, this general description of the real-world utilization of rituximab in patients treated for NHL and CLL at UHS was in line with treatment guidelines and current knowledge on the rituximab safety profile.

Short-Term and Long-Term Results of Endovascular and Open Repair of Abdominal Aortic Aneurysms in Germany

Introduction - Endovascular aortic repair (EVAR) has emerged as a standard of care for abdominal aortic aneurysm repair (AAA). However, real word evidence is limited to compare this technology to open repair (OAR). Major gaps exist related to long-term outcomes of therapies worldwide.

Access to pain management for cancer patients treated under the Brazilian private healthcare system

Objective: To reflect about current pain management in cancer patients treated under the Brazilian Private Healthcare System, considering legal boundaries, access to essential drugs and involved ethical issues. Panelists aimed to reach a consensus about recommendations to increase access to proper analgesia for patients with cancer secondary pain. Methods: Four Brazilian specialists, being a radiation oncologist (and bioethicist), an oncologist, a pain specialist and a CEO of a private healthcare plan, met after the 2019 American Society of Clinical Oncology (ASCO) meeting, held in Chicago, and discussed the aforementioned subjects. A consensus was reached and is described below. Results: Cancer pain is prevailing in our country, probably undertreated, and may be a prevalent cause of medical services overuse, which may increase healthcare costs. Thus, there may be an opportunity to improve patient’s quality of life, with a positive budget impact for private healthcare plans, if this treatment becomes mandatorily reimbursed. There are several studies in the literature showing similar results, but this should be prospectively studied, preferable using real word evidence, at the Brazilian scenario. Cancer pain treatment protocols, designed by specialists, should be designed in agreement with all stakeholders. Conclusion: Panelists agreed that pain treatment, which must be considered a human right, is a clear priority in Brazil. All stakeholders should collaborate in designing protocols to improve patient’s quality of life, consequently improving health insurance’s budgets. If so, this would have clear consequences in access to innovative cancer treatments, as those discussed during the 2019 ASCO meeting.

PRO9 A SYSTEMATIC REVIEW OF THE CLINICAL BURDEN OF IDIOPATHIC MULTICENTRIC CASTLEMAN'S DISEASE

Idiopathic multicentric Castleman’s disease (iMCD) is a rare lymphoproliferative disorder associated with considerable patient suffering and potentially life-threatening complications. Current treatments are limited with the international Castleman Disease Collaborative Network (CDCN) guidelines recommending siltuximab, tocilizumab or rituximab. To identify the clinical burden of disease in adults with MCD who are not infected with HIV and HHV-8, a systematic review was conducted. Medline, Embase and the Cochrane library were searched in December 2018. There were no limits on publication language or study inclusion timeframe. Two reviewers screened articles against pre-defined criteria, a third reviewer resolved discrepancies. One analyst extracted data and another quality-controlled it. The DistillerSR Systematic Review Software was used in the studies selection process. Three clinical trials met inclusion criteria, all using siltuximab. Overall survival (OS) with siltuximab ranged between 100% (year one) and 86-100% (year six). Complete tumour response with siltuximab was between 4-6%, and 25% of siltuximab patients achieved complete symptom response. No placebo-treated patient achieved a complete response. 34% of siltuximab-treated patients and 0% of placebo-treated patients achieved partial durable tumour and symptomatic response. Partial tumour response was reported in 34-48% of siltuximab-treated patients and 0-4% in the placebo arm. For responding subjects, median time to durable tumour and symptomatic response was 155 days vs 65 days (siltuximab vs. placebo, respectively). 38% of patients using placebo discontinued due to adverse events vs. 0-33% of patients on siltuximab. In the three real word evidence studies included, OS varied from 75-100% among tocilizumab-treated patients. 33.3% siltuximab-treated patients with relapsed/refractory iMCD achieved complete response, whereas 25% of tocilizumab-treated patients had complete resolution of symptoms. Studies relating to the treatment adults with MCD who are not infected with HIV and HHV-8 are limited. Of the three CDCN recommended treatments, siltuximab’s use is supported by the strongest evidence in iMCD.

Cost-effectiveness and budget impact analysis of viscosupplementation with hylan G-F 20 for knee and hip osteoarthritis.

PurposeTo estimate the cost-effectiveness and budget impact of viscosupplementation with one intra-articular (IA) injection of 6 mL hylan G-F 20 (Synvisc-One®) and with three injections of 2 mL hylan G-F 20 (Synvisc®3×2) in knee osteoarthritis (OA) patients compared with conventional support therapy (CST – eg, NSAIDs and acetaminophen) and the cost-effectiveness of one IA injection of 2 mL hylan G-F 20 (Synvisc®1×2) in hip OA patients compared with CST from an Italian Health System perspective.MethodsThe model used was a Markov model with states for stages II–IV on the Kellgren–Lawrence scale and runs on 6-month cycles over a 5-year time horizon. A 3.5% discount was applied to both costs and utilities. Direct costs were determined from the perspective of the Italian National Health Service. A one-way and probabilistic sensitivity analysis was conducted for both comparisons.ResultsHylan G-F 20 1×6 mL and hylan G-F 20 3×2 mL for knee OA were very likely to be cost-effective when compared to acetaminophen (ICER = €3,160.61 and €3,845.81 per QALY, respectively) and NSAIDs as both ICERs are below €25,000. The hip OA treatment by hylan G-F 20 1×2 mL was dominant compared to NSAIDs and very likely compared to acetaminophen. The results of the cost-effectiveness analysis were confirmed by one-way sensitivity analysis. The budget impact analysis for knee and hip OA showed a small increase in expenditure during 5 years.ConclusionsHylan G-F 20 1×6 mL/hylan G-F 20 is a cost-effectiveness treatment compared to NSAIDs and acetaminophen in the treatment of knee/hip OA in Italy. The treatment of hip and knee OA resulted in cost-saving with hylan G-F 20 1×2 mL and economically sustainable with hylan G-F 20 1×6 mL. However, Real Word Evidence studies should be conducted in order to estimate costs associated with both prosthetics and to understand the reduction of physiotherapy and medication due to hylan G-F 20.

PDB72 RESOURCES USE AND ECONOMIC IMPACT OF PATIENTS WITH GOUT: REAL WORD EVIDENCE

Determine the resources use and economic impact of patients with gout at the population level. Observational design made from records belonging to 6 primary care centers and 2 hospitals. We included patients’ ≥18 years with an acute episode of gout. The patient follow-up was 2 years. It produced two study groups: patients with 1-2 attacks / acute recurrences and 3 or more. Main variables: demographic, co-morbidity, metabolic syndrome (MS), and resource use and health costs / non-health. Statistical analysis: logistic regression-model ANCOVA, P <0.05. 3,130 with gout were included. Prevalence: 3.3%, mean age: 55.8 years male: 81.1%. For groups: 68.4% had 1-2 acute attacks and 31.6% with 3 or more, p <0.001. The prevalence of MS was 28.8% (confidence interval [CI] 95% CI 27.2 to 30.4%). The average / unit cost was €2,228.6 (direct costs: 96.9%), 90.8% in primary care (visits: 23.5%; drugs: 57.7%). For groups, the average corrected model / unit total cost per patient was €2,130.6 vs. €2,605.4, respectively (P<0.001). In all cost components, the results were higher in the group with ≥3 attacks. The subgroup of diabetic patients (N=641, 20.5%) had a higher cost (compared to €3,124.8€ vs. €1,997.8, P<0.001). Gout is associated with substantial morbidity, presence of MS and resource consumption. The study provides useful data on the cost of the disease, being the costs of outpatient follow the highest.

OP106 The Xpert™ Clostridium difficile Kit Incorporation: Conducting a Local Clinical Study as Part of Hospital Health Technology Assessment

IntroductionThe Xpert™ Clostridium difficile kit is a nucleic acid amplification test indicated after discrepant results from an enzymatic test; was submitted for incorporation in a teaching hospital in Brazil. In order to evaluate the potential for improvement with Xpert™ incorporation, the performance of the available technology (enzymatic test) was assessed using a real word evidence approach. Additionally, the association between enzymatic test results and the agreement to the Infectious Diseases Society of America (IDSA) recommendations for stool test submission (≥ 3 unformed stools in 24 hours without laxatives) for Clostridium difficile were evaluated.MethodsThis is a retrospective cohort study conducted at a tertiary teaching hospital. We included all consecutive tested patients that were submitted for enzyme immunoassay – glutamate dehydrogenase (GDH) plus toxin detection from 15 March to 8 May 2018. Data referent to episodes of unformed stools in 24 hours and use of laxatives were recorded. Statistical significance was tested by Fisher Exact test (α = 0.05).ResultsOne hundred and thirty-eight consecutive patients were tested: 4 (2.9 percent) were positive for GDH and toxin (group III); 114 (82.6 percent) were negative for both (group I). Twenty (14.5 percent) cases were discrepant, all being positive to GDH and negative for toxin (group II). There were not negative GDH and positive toxin cases. The IDSA guidelines were followed in 33 (28.9%), 3 (15%) and 3(75%) test orders in groups I, II and III, respectively (p = 0.03).ConclusionsOnly a minority of patients had discrepant results in enzymatic tests and would be candidates for the Xpert™ test. The low adherence to IDSA guidelines could explain the low positivity rate of enzymatic tests at the hospital. Considering the uncertainty about the potential of the new test for changing infection control practices, Xpert™ was not recommended for incorporation. Using real world evidence data is important for contextualized health technology studies in hospitals.

PCP54 - OVERVIEW OF METHODS FOR ASSESSING COMPARATIVE EVIDENCE FOR TREATMENTS EVALUATED IN EARLY PHASE TRIALS IN ONCOLOGY

For orphan indications and breakthrough therapies, single-arm trials have been used for registration and reimbursement purposes. The use of early phase I studies for comparative effectiveness analyses to support registrational purposes poses a challenge for reimbursement both in terms of selection of data sources for comparators and appropriate methods for analyses. There is no standard analytical approach/methodology for comparative effectiveness analyses in this situation. The first step is determining whether suitable comparative data already exists. This can be accomplished via systematic literature review to identify relevant publications, data sources, and review of available sponsor’s data from older randomised clinical trials on relevant comparators. Administrative databases, electronic medical records, and registries in the United States, Europe, and Asia can be leveraged, however, important data limitations need to be understood and addressed for reliable comparison. The type and number of existing data sources will differ by indication and country and the robustness of the information they can offer is impacted by variability in documentation practices for key outcome measures such as response, progression free, and overall survival. Chart review studies alone, or in combination with secondary data sources, can help overcome data gaps and offer flexibility of collecting additional relevant clinical data to enrich comparisons. Once the data source is identified, the type of analysis can be determined. Matching-adjusted indirect comparison or simulated treatment comparison methods can be leveraged to perform analyses for comparators for which aggregate published data are available. Propensity score matching, or alternatively, regression methods can be used for analyses of pooled patient level data from clinical trial and real word evidence sources. With a rise in number of regulatory and reimbursement submissions using early-phase single arm trials, it is important to understand variety of available methods and the strengths and limitations of each approach for establishing comparative effectiveness.

Real-Word Evidence of Improvement in Quality-of-Life Score, New York Heart Association Class and Tolerability of Valsartan/Sacubitril in Patients with Heart Failure

The PARADIGM-HF study demonstrated that valsartan/sacubitril (Entresto) decreases heart failure (HF) hospitalisation, cardiovascular mortality, and all-cause mortality in patients with HF with reduced ejection fraction [ [1] McMurray J.J.V. Packer M. Desai A.S. Gong J. Lefkowitz M.P. Rizkala A.R. et al. Angiotensin–neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014; 371: 993-1004 Crossref PubMed Scopus (3943) Google Scholar ]. Since the addition of Entresto to the Pharmaceutical Benefit Scheme in June 2017, there has been considerable uptake of this drug. The aim of this study was to assess efficacy, tolerability, and complications of Entresto with real-word evidence. We identified patients who were commenced on Entresto from 1 June 2017 to 30 November 2017 at a tertiary centre in Victoria via pharmacy dispensing database. In total, 33 patients were commenced on Entresto with median age of 65 years, median EF was 31% with 57% secondary to ischaemic cardiomyopathy. Twenty-seven of 33 patients were followed up via telephone/clinic/patient records with three deaths in the time period. There was strong correlation in improvement in quality-of-life scores (EQ-5D), pre versus post: 50 vs 65 (p < 0.05), New York Heart Association (NYHA) class (p < 0.05), and average blood pressure reduction from 119 (range 101–137) to 110 (range 95–125) mmHg since the commencement of Entresto. Starting dose of Entresto was 24/26 mg in 60% of patients and was uptitrated in 37%. Only 14% were able to able to achieve recommenced maximal dose (97/103 mg). The most common side effect was symptomatic hypotension, which led to dose reductions or complete cessation. Our study provides evidence that Entresto results in symptom improvement in addition to blood pressure reduction in patients with heart failure with reduced ejection fraction, as well as common side effects of this drug. Further research is required to demonstrate whether these outcomes are sustained in the longer term.

Economic burden of varicella in children 1\u201312\xa0Years of age in Hungary, 2011\u20132015

BackgroundAlthough live-attenuated varicella-zoster virus (VZV) vaccines have been proven to be safe and effective in preventing varicella and real-word evidence shows routine childhood immunization programs are effective in dramatically reducing varicella associated morbidity and mortality, varicella vaccine is not included in the National Immunization Program (NIP) in Hungary. The purpose of this study was to evaluate the clinical and economic burden associated with varicella in Hungary.MethodsThis was a multicenter, retrospective, chart review study of patients aged 1–12 years with a primary varicella diagnosis between 2011 and 2015. Healthcare resource utilization (HCRU) associated with varicella, unit costs, and work loss were used to estimate direct and indirect costs. All costs are presented in 2015 HUF / Euros (€).Results156 children with varicella were included (75 outpatients, 81 inpatients), with a mean age of 4.4 (SD: 2.0) and 3.7 (SD: 2.1) years, respectively. One or more complications were reported by 12.0% of outpatients and 92.6% of inpatients, the most common being dehydration, skin and soft tissue infections, pneumonia, keratoconjunctivitis, and cerebellitis. HCRU estimates included use of over-the-counter (OTC) medications (96.0% outpatients, 53.1% inpatients), prescription medications (9.3% outpatients, 70.4% inpatients), tests/procedures (4.0% outpatients, 97.5% inpatients), and consultation with allied health professionals (2.7% outpatients, 30.9% inpatients). The average duration of hospital stay (inpatients) was 3.6 (95% CI: 3.2, 4.1) days. The total combined direct and indirect cost per varicella case was 228,146.7 Hungarian Forint (HUF)/€ 736.0 for inpatients and 49,790.6 HUF/€ 106.6 for outpatients. The overall annual cost of varicella in Hungary for children aged <15 years in 2015 was estimated at 1,903,332,524.3 HUF/ € 6,139,980.4.ConclusionVaricella is associated with substantial clinical burden in Hungary, resulting in the utilization of a significant amount of healthcare resources. These results support the need for routine vaccination of all healthy children to reduce the varicella-associated disease burden.

VP02 Are Journal Editors A Barrier To Publication Of Real World Evidence?

INTRODUCTION:Health technology assessment (HTA) bodies often rely heavily upon evidence from peer-review publications to inform their recommendations. Since journal editors attitudes likely influence the types of study designs that are accepted through the peer-review process and on to publication, journal editors serve as gatekeepers to translation of evidence, including real word evidence (RWE), into practice. Given past skepticism of RWE study designs, journal editors perceptions of and possible biases toward RWE are important to understand as they may impact dissemination and, therefore, uptake of research findings. The objective of this study was to examine current views of journal editors regarding the: (i) value of RWE studies and (ii) challenges editors face in managing, reviewing, and publishing RWE manuscripts.METHODS:Journal editors representing general medicine (GM), specialty medicine (SM), health policy/services research (HSR) were invited to participate in a telephone interview, a survey, and an in-person, roundtable discussion.RESULTS:In total, seventy-nine journals were approached, resulting in: 15 interviews (GM = 2; SM = 5; HSR = 8), 17 survey responses (GM = 2; SM = 6; HSR = 9) and 8 roundtable participants. RWE was viewed favorably by interviewed editors (n = 15). Characteristics of high-quality RWE manuscripts included: research question novelty/relevance, rigorous methodology, alignment of data with question, and the extent data-source advantages are optimized. Similar manuscript review processes and challenges were voiced for RWE and other study designs. HSR editors were more likely than SM or GM editors to participate, potentially indicating these researchers are more comfortable or interested in RWE. A possible study limitation was that editors favorable toward RWE may have been more likley to participate.CONCLUSIONS:Peer-review journal editors appear to have favorable views regarding RWE studies and can be accelerators to dissemination of RWE findings. However, they do report that studies and processes could be improved. One suggested improvement included a checklist for editors to speed rejections and improve communications with authors.