Review Of Real-world Data Research Articles

Where do patients die when there is no hospice? Real-world data.

235 Background: The role of real-world data has been shown to be of vital importance in cancer clinical research in recent years. Furthermore, palliative and end of life care is rarely studied outside the real world setting. Lastly, Greece lacks any significant palliative care or services and the law does not recognize advance directives. Methods: We conducted a retrospective review of real world data derived from the medical files of the deceased patients of our group, in order to assess where patients in Greece die given the lack of hospice facilities. We routinely collect the cause and place of death for all patients as well as the source of the information of the patient's passing prospectively. We then retrospectively collected the date of diagnosis and cancer type. Results: Between 04/01/2019 and 01/30/2022, we collected information regarding the cause and place of death of patients that had been under clinical care in our oncology department. During this time period, 454 patient deaths occurred, of which 54.67% were male and 45.33% female. The median age of death was 63.85 years and the most frequent cause of death was disease progression (76,21%), with only 1,98% of our patients having lost their lives due to toxicity of anticancer treatment. Importantly, the majority of our patients were hospitalized at the time of death in contrast to 23.79% that passed away at home. Data regarding cancer type and overall survival since diagnosis are being processed. Conclusions: Because of the lack of specialized facilities providing end of life care in Greece, most of our patient choose or are forced to spend the last days of their life in general tertiary care hospitals, a situation which might be indicative of both the socio-economic characteristics of our country and the lack of awareness of the necessity of this healthcare infrastructure. Further analysis is pending regarding associated parameters.

Effects of GLP-1RAs on cardiovascular outcomes in patients with type 2 diabetes mellitus: review of real-world data on target populations from diabetes registry in Russian Federation

RATIONALE. Over the past 20 years the prevalence of type 2 diabetes in Russia has more than doubled and reached 4.43 million people in 2020, while the growth rate keeps increasing. Most patients with T2DM are at a higher risk of developing major adverse cardiovascular events (MACE) associated with significant mortality. There is a strong evidence base that the drugs belonging to GLP-1RA class contribute to reducing the risk of cardiovascular events and renal outcomes. At the same time, the current prescribing rates of these treatments in Russia are quite low - only about 0.1% of patients are prescribed GLP-1RAs, according to Diabetes Registry data.AIM. Review the results of several randomized clinical trials (RCTs) concerning effects of GLP-1RA treatments on prevention of primary and secondary cardiovascular events and estimate the number of diabetic target population.MATERIALS AND METHODS. We examined the data from clinical trials on GLP-1RA treatments registered in Russia and used in routine clinical practice (ELIXA, EXSCEL, LEADER, SUSTAIN-6 and REWIND) and data from two meta-analyzes published as of December 1, 2020. The task was to evaluate the inclusion criteria, patient profile, and the clinical efficacy and safety profiles of the studied therapies. Also, the analysis of clinical information from the Diabetes Registry (DR) was performed to estimate the number of target T2DM patients meeting RCTs inclusion criteria that could benefit from prescribing of GLP-1RAs.RESULTS. The reviewed clinical trials demonstrated a statistically significant reduction (p <0.05) in the risk of serious cardiovascular events in patients treated with Liraglutide [RR 0.87 (95% CI, 0.78-0.97)], Semagltuide [OP 0.74 (95% CI 0.58-0.95)] and Dulaglutide [RR 0.88 (95% CI 0.79-0.99)]. Meta-analyzes utilizing data from 6 RCTs with the total number of 56,004 T2DM patients, also, confirmed a statistically significant reduction in the risk of developing MACE (by 12%) in the studied population, and a 17% reduction in the risk of combined renal outcomes [RR 0.83 (95% CI 0.78-0.89), p <0.0001]. The DR patient population that met the RCTs inclusion criteria amounted to 538.6 thous. subjects in case of REWIND and 432.4 thous. in case of LEADER and SUSTAIN-6. The key differences between FDR patients and patients engaged in RCTs included gender and age characteristics. The DR patients were generally older and the bulk of them were women, which has to do with overall Russian demographic trends. The proportion of DR patients with established CVD was 26%, which closely matched the profile of patients from REWIND study (31.5%). According to DR data, the number of patients in whom the treatment was intensified following prescription of basal insulin was 7612 per year, which is close to a potential cohort eligible for alternative treatment with GLP-1RAs.CONCLUSION. All the drugs belonging to GLP-1RA class are clinically effective in reducing the risk of cardiovascular and renal outcomes, while demonstrating a favorable safety profile including with respect to lower risk of developing hypoglycemia. The decreased risk of complications was recorded both in patients with existing cardiovascular risks and patients with established CVD. Of all GLP-1RA treatments available in Russia at this point, the greatest clinical effectiveness is achieved by Liraglutide, Semaglutide and Dulaglutide. The estimated patient population from DR, meeting RCTs inclusion criteria and matching RCTs patient profile was over 500, 000 people with the largest number of patients meeting the REWIND criteria. The target population of patients with T2DM who may potentially benefit from the administration of GLP-1RAs is over 500, 000 people. Out of that number at least 7.5 thousand are patients, whose treatment is intensified following prescription of basal insulin (with an aim of improving glycemic control, but without consideration of cardiovascular risks).Currently, if we take the real world clinical setting in Russia, the number of patients receiving GLP-1RA treatments is substantially lower than the estimated figures (less than 1%), which requires reconsideration of the approach toward their prescribing as is recommended by state-of-the-art clinical guidelines prioritizing prevention of cardiovascular risks.

FDA Oncology Center of Excellence Review of Real World Data Submissions Supporting Drug Development in Hematologic Malignancies

BackgroundAligning with 21st Century Cures legislation, FDA is exploring methodologies to advance appropriate uses of Real World Data (RWD) to generate Real World Evidence (RWE). RWD to support regulatory decision making has markedly increased in oncology. This review specifically focused on the analysis of RWD containing submissions for medical products in development for the treatment of hematological malignancies and associated treatment related conditions (e.g., Cytokine Release Syndrome (CRS), Graft Versus Host Disease (GVHD).MethodsA systematic search was conducted using internal FDA databases to identify RWD submissions from 2010 to 2020. Search terms included: real world evidence, real world data, electronic health record, cancer registry, administrative claims, external control arm, observational cohort, historical control arm, real world Overall Survival (rwOS) , real world Response Rate (rwRR), real world Overall Response Rate rwORR and real world Complete Response (rwCR). Regulatory submissions specific to malignant hematology and associated treatment related conditions were reviewed, and pre-defined common data elements were extracted and validated by independent dual review. Descriptive statistics were calculated.ResultsA total of 142 regulatory submissions included RWD from 2011-2020. A subset of 94 RWD submissions met the criteria for further evaluation, of which 20 (21%) submissions corresponding with 14 molecular entities were for hematologic malignancies or treatment related conditions (e.g., CRS, GVHD). RWD submissions increased substantially over time, with 14 (70%) of submissions received between 2019-2020. Specific evaluation for pediatric indications was referenced in 15% of submissions. The most commonly referenced RWD source was EHR data (55%), followed by use of multiple sources (20%), and registry data (15%). Approximately 90% of the submissions aimed to support treatment effectiveness. Primary RWD study objectives included supporting approval of a new molecular entity (NME) (40%), expanding an approved indication (25%), conversion from accelerated to regular approval (15%), and providing data to inform postmarketing safety evaluation (20%). Among RWD submissions, response endpoints (e.g., rwORR, rwCR, rwPR, Partial Response) and overall survival (e.g., rwOS) were most frequently selected as primary outcomes for 50% and 20% of proposals respectively; however, these outcomes were included as any endpoint in 65% and 75% of submissions.ConclusionThis review demonstrates increasing use of various RWD sources to support evidence generation for drug development in hematologic malignancies and associated treatment related conditions with the primary objective of supporting demonstration of effectiveness using rwOS or real world response measures as primary endpoints. Given the increased inclusion of RWD in regulatory submissions, further methodological development is needed, including in the selection and validation of rwEndpoints. Appropriate study design must be aligned with a clear regulatory objective to ensure that RWD can be adequately evaluated. Additionally, the development of standardized metrics for data characterization and transparency in reporting of RWD are foundational steps to the evaluation of fit for purpose RWD to support regulatory decision making. DisclosuresNo relevant conflicts of interest to declare.

Myocarditis as a rare, yet serious adverse event associated with immune checkpoint inhibitors in patients with non-small cell lung cancer: Case series from a large community-based cancer center.

e21047 Background: Patients (pts) with lung cancer and other cancers treated with immune checkpoint inhibitors (ICI) may experience immune related adverse events (irAE). These can present with variable severity and with single- or multi-organ involvement including pneumonitis, colitis, hepatitis, and myocarditis/pericarditis. The incidence of myocarditis has been reported between 0.06% and 2.4% and is associated with a high mortality (25% to 50%). This retrospective review of real-world data (RWD) investigates myocarditis as a high-grade adverse event in pts with lung cancer treated with ICIs. Methods: Pts were identified and characterized using RWD in the Syapse Learning Health Network platform from 2010 to 2020 at Advocate Aurora Health Care. Eligible pts included: ≥18 years old; histologically confirmed NSCLC; and myocarditis diagnosis by ICD codes. Additional chart review was performed to confirm timing of ICI treatment and myocarditis. All pts identification and review were performed after IRB review. Results: 12,686 pts with non-small cell lung cancer were eligible for review. The median age at diagnosis was 70; 54% were female; 86% were White and 12% were Black; 1,975 (15.6%) were treated with an ICI and of those 4 cases (0.2%) of myocarditis were identified. All 4 pts were White females, ages 46, 59, 65, and 74 years. Pathology included lung adenocarcinoma (3) and an undifferentiated lung carcinoma (1). All pts had metastatic disease, and none had a prior history of cardiac disease. ICIs were pembrolizumab (2), durvalumab (1), and nivolumab (1). Median time from initial dose of ICI to diagnosis of myocarditis was 62 days [range: 42-185]. All 4 pts presented with chest pain and elevated troponin T [median 0.07 ng/ml (range: 0.06-0.08)]. All pts had echocardiography at the time of diagnosis, and 2 pts had cardiac MRI that confirmed myocarditis. 3 pts were treated with a prednisone taper. 1 pt died of recurrent congestive heart failure and ventricular tachycardia despite rescue attempt with high dose corticosteroids. 2 pts had additional concomitant irAEs of hypothyroidism/colitis, and thyroiditis/pneumonitis, respectively. Conclusions: Many irAEs are reversible. This RWD analysis confirms that clinically evident myocarditis is a rare but serious adverse event of ICI therapy. Early consideration, diagnosis, and intervention may help prevent poor outcomes. Termination of ICI therapy along with initiation of corticosteroids constitute the current standard of management. Further research is warranted to better identify high risk groups, surveillance measures, and improved management of ICI associated myocarditis.