Real-world Evidence Research Articles

Supplementing systematic review findings with healthcare system data: pilot projects from the Agency for Healthcare Research and Quality Evidence-based Practice Center program

ObjectivesThe US Agency for Healthcare Research and Quality, through the Evidence-based Practice Center (EPC) Program, aims to provide health system decision makers with the highest-quality evidence to inform clinical decisions. However, limitations in the literature may lead to inconclusive findings in EPC systematic reviews (SRs). The EPC Program conducted pilot projects to understand the feasibility, benefits, and challenges of utilizing health system data to augment SR findings to support confidence in healthcare decision-making based on real-world experiences. Study Design and SettingThree contractors (each an EPC located at a different health system) selected a recently completed SR conducted by their center and identified an evidence gap that electronic health record (EHR) data might address. All pilot project topics addressed clinical questions as opposed to care delivery, care organization, or care disparities topics that are common in EPC reports. Topic areas addressed by each EPC included infantile epilepsy, migraine, and hip fracture. EPCs also tracked additional resources needed to conduct supplemental analyses. The workgroup met monthly in 2022-2023 to discuss challenges and lessons learned from the pilot projects. ResultsTwo supplemental data analyses filled an evidence gap identified in the SRs (raised certainty of evidence, improved applicability) and the third filled a health system knowledge gap. Project challenges fell under three themes: regulatory and logistical issues, data collection and analysis, and interpretation and presentation of findings. Limited ability to capture key clinical variables given inconsistent or missing data within the EHR was a major limitation. The workgroup found that conducting supplemental data analysis alongside an SR was feasible but adds considerable time and resources to the review process (estimated total hours to complete pilot projects ranged from 283 to 595 across EPCs), and that the increased effort and resources added limited incremental value. ConclusionSupplementing existing SRs with analyses of EHR data is resource intensive and requires specialized skillsets throughout the process. While using EHR data for research has immense potential to generate real-world evidence and fill knowledge gaps, these data may not yet be ready for routine use alongside SRs.

"Real-world Evidence Requirements with Respect to External Control Arms of Single-arm Clinical Trials by Major Regulatory and HTA Agencies – Comparative Review of Guidelines and Identification of Trends Based on Seven Recent Case Studies"

"Real-world Evidence Requirements with Respect to External Control Arms of Single-arm Clinical Trials by Major Regulatory and HTA Agencies – Comparative Review of Guidelines and Identification of Trends Based on Seven Recent Case Studies"

Utilization of Real-World Data to Facilitate Clinical Trials for Patients with Lymphoma

The future directions in leveraging real-world evidence (RWE) and real-world data (RWD) in the field of lymphoma, as compared to traditional experimental clinical trials, are poised to significantly impact research methodologies, treatment strategies, and patient care. Current methods of clinical trials involve a well-controlled design and patient selection bias. Integrating RWE and RWD with experimental clinical trials offers a multifaceted approach to understanding lymphoma and enhancing patient outcomes. In this review, we discuss how RWE has helped shape lymphoma clinical trials, and we compare and evaluate evidence obtained from real-world lymphoma studies/databases with that obtained from clinical trials. We also discuss methods for utilizing surrogate endpoints to facilitate clinical trials and expedite drug development. RWE can be leveraged to bridge the gap between data obtained from clinical trial populations and the broader patient population encountered in clinical practice, by highlighting differences in outcomes and the need for effective treatment strategies across diverse patient groups.

First-Line Combination with Proteasome Inhibitor-Based Treatment and Zoledronic Acid Is Effective in Reducing Later Fractures in Multiple Myeloma Irrespective of Multiple Myeloma Bone Disease at Diagnosis.

The present study provides real-world evidence on the treatment of multiple myeloma (MM) bone disease with various bisphosphonates combined for different myeloma-specific treatments as no validated data regarding the best combination treatment for bone disease associated with MM are available. We examined retrospectively 345 MM patients treated with autologous stem cell transplantation in Finland during 1996-2020. The median age of the patients was 60 years with a median follow-up time of 50 months (1-339). At diagnosis, 72.1% of the patients had myeloma-associated bone disease and 45.8% had fractures. Most patients (58.8%) received proteasome inhibitor (PI)-containing treatment at first line. MM bone disease was treated in 91.6% of the patients; 49.9% received zoledronic acid (ZA) and 29.9% pamidronate. Inferior overall survival was associated with MM bone disease at diagnosis (p = 0.005) or a fracture at diagnosis (p = 0.003). A later fracture was identified in 29% of the patients, and in those patients without MM bone disease at diagnosis later fractures were less common after ZA treatment (p = 0.049). PI-based treatment plus ZA (p = 0.019) seemed to be the best combination to prevent later fractures, even though the same patient subgroup was more likely to experience relapse (p = 0.018), and also when excluding patients with previous induction therapy without novel agents (p = 0.008). To conclude, this study suggests that the best therapy to prevent later fractures in MM might be PI-based treatment combined with ZA.

Estimation of the Clinical, Economic, and Social Burden of Stage IV Non-Small Cell Lung Cancer in Mexico.

Lung cancer continues to be the leading cause of death among cancer patients worldwide. This study aimed to estimate the clinical, economic, and social burdens of stage IV non-small cell lung cancer (NSCLC) in private and public healthcare centers in Mexico, utilizing real-world evidence. The study population included patients >18 years of age diagnosed with stage IV NSCLC who received cancer treatment at the Centro Médico Nacional Siglo XXI (IMSS), the Centro Médico Nacional "20 de Noviembre" (ISSSTE), the Mexican Institute of Respiratory Diseases (INER), and the Medical Center ABC (American British Cowdray) from 1 January 2019 to 31 December 2020. The analysis included evaluation of epidemiological data, treatment regimens, and clinical outcomes, and emphasized pharmacological and non-pharmacological treatments, including detailed follow-up investigations, as part of comprehensive clinical management. Additionally, the study assessed the social burden through variables such as working-age absenteeism and presenteeism and caregiver productivity loss, as well as economic burden, considering both clinical and social components, with costs adjusted to 2022 Mexican pesos (MXN) values. A total of 188 patients with metastatic NSCLC were studied. The main type of NSCLC tumor found in the sample was adenocarcinoma (81%). Treatment regimens included pharmacological treatments (78%), non-pharmacological treatments (25%), and palliative care (24%). Complications were present in 73% of the cohort, while 60% presented adverse events. Clinical management costs of up to MXN1,001,579 per patient in the public sector and MXN2,140,604 in the private sector were reported. It was estimated that working-age patients lose 84-335 days yearly due to absenteeism and presenteeism, while caregivers report a productivity loss equivalent to 13-30 days due to the management of NSCLC patients. These indirect costs of NSCLC contribute to the social burden. A working-age patient with stage IV disease is associated with an average indirect cost of MXN49,731-178,287 in public institutions, while in private institutions, the cost elevates to MXN438,103. This study highlights the substantial clinical, economic, and social burdens of stage IV NSCLC in Mexico, revealing significant disparities between public and private healthcare sectors. It underscores the urgent need for standardized practices and equitable care across all systems.

Development and validation of an individual risk prediction tool for severe respiratory syncytial virus infection among children under five years in China

Objective: To construct a predictive model to assess the risk of severe respiratory syncytial virus infection among children under five years in China, conduct preliminary validation of this model by using external data, and develop an individual risk assessment tool available for their parents. Methods: The admission after RSV infection was used as a marker of severe infection. Based on the evidence of RSV hospitalization-related risk factors and real-world data, such as the prevalence of various risk factors in children under five years old in China, a Monte Carlo-based individual RSV hospitalization risk prediction model for children under five years old was constructed. Taking Suzhou City as an example, the model was externally validated, and an interactive risk prediction tool (RSV HeaRT) was developed on the WeChat mini-program platform. Results: The estimation model showed that in children under five years old in China if the population did not have any risk factors for severe RSV infection, the RSV annual hospitalization rate was 2.2/1 000 (95%CI: 0.9/1 000-7.5/1 000). Based on this baseline hospitalization rate and the prevalence of related risk factors in Suzhou, the model predicted an RSV hospitalization rate of 8.0/1 000 (95%CI: 4.6/1 000-24.4/1 000) for children under five years old annually in Suzhou, which was close to the reported RSV hospitalization rate in literature (10/1 000-20/1 000). In the developed RSV HeaRT WeChat mini-program, target users (such as parents of children) could input basic information, disease history, and social environmental factors of the child into the mini-program, and the tool could provide real-time feedback on the following predicted results: First, the relative risk of hospitalization due to RSV infection in current children compared to general children; Second, the probability of hospitalization due to RSV infection within the next year; Third, the relative risk of adverse outcomes during hospitalization in the event of RSV infection. Conclusion: This study is based on real-world evidence related to RSV hospitalization risk and constructs an RSV hospitalization risk prediction model suitable for Chinese children based on the combination of the current prevalence of risk factors in children under five years old in China. The accuracy of the prediction model results has been preliminarily demonstrated. Based on this design, the RSV HeaRT developed can facilitate parents to evaluate the hospitalization risk of children.

Effectiveness of acupuncture in treating patients with pain and mental health concerns: the results of the Alberta Complementary Health Integration Project.

This study presents real-world evidence on the clinical outcomes of the Alberta Complementary Health Integration Project (ABCHIP), which utilized acupuncture to address pain and mental health issues in two vulnerable populations in Alberta: youth (aged 24 and below) and elderly (aged 55 and above). Over 282 days, a total of 606 patients received 5,424 acupuncture treatments. Tailored to each patients' specific pain and mental health concerns, an individualized treatment plan was selected, following a standard treatment protocol lasting 1 to 3 months. Patients were evaluated at least twice: initially and upon completing therapy. Primary treatment outcomes were assessed using various measures, including the Brief Pain Inventory (BPI), Pittsburgh Sleep Quality Index (PSQI), Patient Health Questionnaire 9 (PHQ9), PROMIS Anxiety 8a and its pediatric form PROMIS Anxiety-Pediatric, PROMIS Short Form v1.0 Fatigue 8a and its pediatric counterpart PROMIS Pediatric Short Form v2.0 Fatigue 10a, PROMIS Short Form v1.1 Anger 5a and its version PROMIS SF v2.0 5a, and EQ-5D-5L. These measures gauged pain reduction, improved sleep quality, reduced depression, anxiety, fatigue, anger, and quality of life, respectively. Analysis of data from 500 patients who received at least 6 acupuncture sessions through ABCHIP showed statistically significant improvements in clinical outcomes. Among this group, the subgroup of 235 patients who received at least 12 sessions demonstrated the most favorable treatment outcomes, including an 75.5% reduction in pain severity, a 53.1% improvement in sleep quality, a 78.4% drop in depression, a 41.1% decline in anxiety, a 43.7% decrease in fatigue, a 38.2% decrease in anger, and a 42.6% improvement in overall quality of life. Integrating acupuncture with usual care demonstrates promise in enhancing mental health, alleviating chronic and general pain, and improving overall quality of life. The findings suggest that integrative programs, such as ABCHIP, present an effective approach to addressing pain and mental health concerns in vulnerable populations, providing valuable insights for future healthcare interventions.

Pembrolizumab in Patients with Advanced Urothelial Carcinoma with ECOG Performance Status 2: A Real-World Study from the ARON-2 Project.

The benefit of immune checkpoint inhibitors (ICIs) for poor performance status patients with advanced urothelial carcinoma (UC) remains unknown. In the present sub-analysis of the ARON-2 study, we investigated the role of pembrolizumab for advanced UC patients with ECOG (Eastern Cooperative Oncology Group) performance status (ECOG-PS) 2. Patients aged ≥18 years with a cytologically and/or histologically confirmed diagnosis of advanced UC progressing or recurring after platinum-based therapy and treated with pembrolizumab between 1 January 2016 to 1 April 2024 were included. In this sub-analysis we focused on patients with ECOG-PS 2. We included 1,040 patients from the ARON-2 dataset; of these, 167 patients (16%) presented an ECOG-PS 2. The median overall survival (OS) was 14.8 months (95% confidence interval (CI) 12.5-16.1) in the overall study population, 18.2 months (95% CI 15.8-22.2) in patients with ECOG-PS 0-1, and 3.7 months (95% CI 3.2-5.2) in subjects with ECOG-PS 2 (p<0.001). The median progression-free survival (PFS) in the overall study population was 5.3 months (95% CI 4.3-97.1), 6.2 months (95% CI 5.5-97.1) in patients with ECOG-PS 0-1, and 2.8 months (95% CI 2.1-3.4) in patients with ECOG-PS 2. Among the latter, liver metastases and progressive disease during first-line therapy were significant predictors of OS at both univariate and multivariate analyses. For PFS, univariate and multivariate analyses showed a prognostic role for lung metastases, liver metastases, and progressive disease during first-line therapy. This large real-world evidence study suggests the effectiveness of second-line pembrolizumab for mUC patients with poor performance status. The presence of liver metastases and progressive disease during first-line therapy is associated with worse clinical outcomes and, thus, should be taken into account when making treatment decisions in clinical practice.

Real-world pharmacovigilance analysis of galsulfase: a study based on the FDA adverse event reporting system (FAERS) database.

Associated with enzyme deficiencies causing glycosaminoglycans (GAGs) accumulation, mucopolysaccharidosis type VI (MPS VI) is lysosomal storage disorder. In the treatment of MPS VI, galsulfase (Naglazyme) is commonly used as an enzyme replacement therapy (ERT). There remains a need for comprehensive real-world data on its safety and associated adverse events (AEs). An analysis of the FDA Adverse Event Reporting System (FAERS) database will be conducted to identify potential risks and adverse reactions associated with galsulfase in real-life settings. The FAERS database was used to extract data from Q2 2005 to Q4 2023. A total of 20,281,876 reports were analyzed after duplicate elimination, with 3,195 AE reports related to galsulfase identified. The association between galsulfase and AEs was investigated by utilizing four algorithms: reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS). The analysis focused on the timing of onset, signs of AEs, and clinical significance. Twenty seven organ systems were involved, and significant system organ classes (SOCs) included respiratory, thoracic and mediastinal disorders, and infections and infestations. At the PT level, 72PTs corresponding to 15 SOCs were identified, with some AEs not previously mentioned in the product label. AEs associated with galsulfase had a median onset time of 1,471days, with over half of the cases occurred within the first 5years of treatment initiation. This investigation delivers an exhaustive and indicative assessment of galsulfase's safety profile, grounded in authentic, real-world evidence. The findings emphasis the importance of continuous safety surveillance and the emergence of new AEs. The identification of previously unreported urologic adverse events, such as glomerulonephritis membranous and nephritic syndrome, warrants further investigation. The study emphasizes the need for enhanced pharmacovigilance to ensure patient safety and the effectiveness of galsulfase treatment.

A large-scale observational comparison of antidepressants and their effects

BackgroundSelective Serotonin Reuptake Inhibitors (SSRIs) represent a diverse class of medications widely prescribed for depression and anxiety. Despite their common use, there is an absence of large-scale, real-world evidence capturing the heterogeneity in their effects on individuals. This study addresses this gap by utilizing naturalistic search data to explore the varied impact of six different SSRIs on user behavior. MethodsThe study sample included ∼508 thousand Bing users with searches for one of six SSRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline) from April–December 2022, comprising 510 million queries. Cox proportional hazard models were employed to examine 30 topics (e.g., shopping, tourism, health) and 195 health symptoms (e.g., anxiety, weight gain, impotence), using each SSRI as a reference. We assessed the relative hazard ratios between drugs and, where feasible, ranked the SSRIs based on their observed effects. We used Cox proportional hazard models in order to account for both the likelihood of users searching for a particular topic or symptom and the associated time to that search. The temporal aspect aided in distinguishing between potential symptoms of the disorder, short-term medication side effects, and later appearing side effects. ResultsDifferences were found in search behaviors associated with each SSRI. E.g., fluvoxamine was associated with a significantly higher likelihood of searching weight gain compared to all other SSRIs (HRs 1.85–2.93). Searches following citalopram were associated with significantly higher rates of later impotence queries compared to all other SSRIs (HRs 5.11–7.76), except fluvoxamine. Fluvoxamine was associated with a significantly higher rate of health related searches than all other SSRIs (HRs 2.11–2.36). ConclusionsOur study reveals new insights into the varying SSRI impacts, suggesting distinct symptom profiles. This novel use of large-scale, naturalistic search data contributes to pharmacovigilance efforts, enhancing our understanding of intra-class variation among SSRIs, potentially uncovering previously unidentified drug effects.

Use of Sensitivity Analyses to Assess Uncontrolled Confounding from Unmeasured Variables in Observational, Active Comparator Pharmacoepidemiologic Studies: A Systematic Review.

Understanding the potential for, direction, and magnitude of uncontrolled confounding is critical for generating informative real-world evidence. Many sensitivity analyses are available to assess robustness of study results to residual confounding, but it is unclear how researchers are using these methods. We conducted a systematic review of published active comparator cohort studies of drugs or biologics to summarize use of sensitivity analyses aimed at assessing uncontrolled confounding from an unmeasured variable. We reviewed articles in five medical and seven epidemiologic journals published between January 1, 2017, and June 30, 2022. We identified 158 active comparator cohort studies, 76 from medical and 82 from epidemiologic journals. Residual, unmeasured, or uncontrolled confounding was noted as a potential concern in 93% of studies, but only 84 (53%) implemented one or more sensitivity analysis to assess uncontrolled confounding from an unmeasured variable. The most common analyses were E-values among medical journal articles (21%) and restriction on measured variables among epidemiologic journal articles (22%). Researchers must rigorously consider the role of residual confounding in their analyses and the best sensitivity analyses for assessing this potential bias.

Real-World Data and Real-World Evidence in Healthcare in the United States and Europe Union.

The use of real-world data (RWD) for healthcare decision-making is complicated by concerns regarding whether RWD is fit-for-purpose or is of sufficient validity to support the creation of credible RWE. An efficient mechanism for screening the quality of RWD is needed as regulatory agencies begin to use real-world evidence (RWE) to inform decisions about treatment effectiveness and safety. First, we provide an overview of RWD and RWE. Data quality frameworks (DQFs) in the US and EU were examined, including their dimensions and subdimensions. There is some convergence of the conceptual DQFs on specific assessment criteria. Second, we describe a list of screening criteria for assessing the quality of RWD sources. The curation and analysis of RWD will continue to evolve in light of developments in digital health and artificial intelligence (AI). In conclusion, this paper provides a perspective on the utilization of RWD and RWE in healthcare decision-making. It covers the types and uses of RWD, data quality frameworks (DQFs), regulatory landscapes, and the potential impact of RWE, as well as the challenges and opportunities for the greater leveraging of RWD to create credible RWE.

Tele-Assisted Home-Based Palliative Care Reduces Health Care Costs for Terminal Cancer Patients: Real-World Evidence From a Regional Hospital in Taiwan.

Background: Tele-assisted home-based palliative care (THPC) usually fulfills the desire of terminal patients to pass away at home. The overall costs of such a service deserve evaluation. Objectives: This study aims to determine health care utilization and costs for cancer patients at the end of life, stratified by THPC service. Design: Patients who received THPC were matched 1:1 based on age, gender, year of death, and propensity score with those who did not receive THPC. Setting/Subjects: A total of 773 cancer patients passed away in a regional hospital in Taiwan during the period of 2012-2020, of which 293 received THPC. Measurements: We measured the rates and costs of outpatient clinic visits, emergency department (ED) visits, hospitalizations, and intensive care unit (ICU) admissions during the last week, the last two weeks and the last month before death. In addition, we estimated the driving times and expenses required for transportation from each cancer patient's home to the hospital using Google Maps. National Health Insurance (NHI) reimbursements and out-of-pocket expenses were also calculated. Results: In comparison with patients without THPC, those who received THPC had a 50% lower likelihood of visiting the ED or being hospitalized, a more than 90% reduced chance of ICU admission, but were four times more likely to obtain their medicines from outpatient clinics. THPC patients had similar out-of-pocket expenditures, approximately half of the NHI costs, and lower rates and costs for ambulance transportation to the ED. Conclusions: THPC reduced health care costs for terminal cancer patients in the last week, the last two weeks, and the last month before death, while also increasing the likelihood of patients being able to rest and pass away at home.

Palbociclib in HR-Positive, HER2-Negative Advanced/Metastatic Breast Cancer: A Systematic Scoping Review of Real-World Evidence from Countries Outside of Western Regions that Are Underrepresented in Clinical Trials.

Limited awareness exists regarding real-world data (RWD) for palbociclib in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced/metastatic breast cancer in populations from certain countries outside of Western regions. A systematic scoping review was conducted using PubMed and Embase to evaluate RWD for palbociclib from countries outside of Western regions that are underrepresented in clinical trials. Search criteria were aligned with our research question for relevant English-language publications, without restrictions on publication date, followed by Phase 1 (title and abstract) and Phase 2 (full-text) screening of retrieved citations as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data analyses of eligible studies were done separately for abstracts and full-text publications to enhance the precision and reliability of the results. Database search yielded 1485 non-duplicate records, 46 qualified for inclusion, of which 47.8% were published as full text. The analysis of outcomes, based exclusively on full-text publications that collectively included 2048 patients treated with palbociclib, revealed the median progression-free survival (PFS) of 20.2-36.7months, overall survival (OS) of 39.9months (reported in one publication) and objective response rate (ORR) of 45.3-80.0% with first-line treatment. In ≥ second line, the median PFS, OS and ORR ranged from 7.0 to 24.2months, 11 to 19.6months, and 13.9% to 47.9%, respectively. The safety profile of palbociclib was similar to that reported in pivotal clinical studies, and no new safety concerns were identified. A comprehensive volume of evidence demonstrates that palbociclib's effectiveness and safety profile in real-world settings align with those observed in clinical trials, offering valuable insights for clinical decision-making in countries outside of Western regions underrepresented in clinical trials.

Effects of concurrent optical and magnetic stimulation in hard-to-heal wounds: a real-world evidence case series.

This work explores concurrent optical and magnetic stimulation (COMS) effects on hard-to-heal wounds in real-world settings. In this case series, participants received COMS 1-3 times per week for up to 12 weeks alongside standard wound care. A total of 27 patients (18 female and nine male) were included. Mean age was 72 years. Participants' wounds that were unresponsive to standard wound care included: venous leg ulcers (VLUs, n=13); mixed leg ulcers (MLUs, n=4); diabetic foot ulcers (DFUs, n=1); pressure ulcers (PUs, n=5); and traumatic wounds (TWs, n=4). On average, COMS was applied twice a week, resulting in an overall mean wound area reduction of 69%. In 24 participants, COMS was used primarily to achieve wound closure by the end of the 12-week period, of which: 12 were classified as complete wound closure (50%; VLUs=8, PUs=3 and TW=1); four as likely-to-heal (17%; VLUs=2 and MLUs=2); four as 'improved' (17%; MLU=1, DFU=1 and TWs=2); and four as 'non-responding' (17%; VLUs=3 and MLU=1). The best results were achieved in PUs and VLUs (respectively 100% and 62% categorised as completely healed). When used in participants where its purpose was other than that of achieving wound closure, COMS was successfully used to debride two PUs, and for wound bed preparation in one TW. In this case series, COMS showed positive effects and appeared to be beneficial in healing different types of hard-to-heal wounds in community health and homecare settings. Novel COMS therapy aspects emerged: (1) positive outcomes for PU and VLU treatment; (2) COMS as a potential debridement tool when sharp debridement is unfeasible; and (3) COMS as a promising method to prepare wound beds for subsequent skin grafting or skin replacement procedures.

Real-world evidence to support regulatory submissions: Alandscape review and assessment of use cases.

Real-world evidence (RWE) has an increasing role in preapproval settings to support the approval of new medicines and indications. The main objectives of this study were to identify and characterize regulatory use cases that utilized RWE and other related observational approaches through targeted review of publications and regulatory review documents. After screening and inclusion/exclusion, the review characterized 85 regulatory applications with RWE. A total of 31 were in oncology and 54 were in non-oncology therapeutic areas. Most were for indications in adults only (N = 42, 49.4%), while 13 were in pediatrics only (15.3%), and 30 were in both (35.3%). In terms of regulatory context, 59 cases (69.4%) were for an original marketing application, 24 (28.2%) were for label expansion, and 2 (2.4%) were for label modification. Most also received special regulatory designations (e.g., orphan indication, breakthrough therapy, fast track, conditional, and accelerated approvals). There were 42 cases that utilized RWE to support single-arm trials. External data to support single-arm trials were utilized in various ways across use cases, including direct matching, benchmarking, natural history studies as well as literature or previous trials. A variety of data sources were utilized, including electronic health records, claims, registries, site-based charts. Endpoints in oncology use cases commonly included overall survival, progression-free survival. In 13 use cases, RWE was not considered supportive/definitive in regulatory decision-making due to design issues (e.g., small sample size, selection bias, missing data). Overall, RWE is utilized in regulatory approval processes for new indications/label expansion across various therapeutic areas with wide range of approaches. Multifaceted cross-sector efforts are needed to further improve the quality and utility of RWE in regulatory decision-making.

Intrathecal ziconotide for the treatment of chronic pain: a collection of clinical experiences and literature review.

Despite the wide use of ziconotide in the USA for treating refractory cancer- and noncancer-related pain, this agent is little used in Europe, even if licensed by the European Medicines Agency (EMA). The reason could be attributed to the high, fixed starting dose required for ziconotide, as stated in the EMA Summary of Product Characteristics (SmPC). This dosage recommendation is based on the results of pivotal clinical studies of ziconotide, which utilized aggressive titration schedules. Thus, a reappraisal of the available evidence, as well as a reflection on real-life clinical experiences, might be useful to identify practice adjustments to improve the clinical application of ziconotide in the European scenario. In line with this need, this paper reports some clinical experiences of patients with chronic pain treated with ziconotide intrathecal (IT) therapy in Italy, particularly focusing on long-term treatment to further characterize and improve the use of this agent in real practice. Moreover, a literature review of the available data on the effectiveness and safety of IT ziconotide is provided. Collected clinical experiences suggested that the use of IT ziconotide represents a valuable option, particularly in cases where other treatments have been ineffective or poorly tolerated. Ziconotide was shown to not cause severe side effects in the long-term treatment, leading to a constant pain relief effect at stable doses, without adverse events that caused therapy interruption. The overall constant ziconotide dosages also suggest the absence of a tolerance effect. In parallel, the evidence in the literature aligns with real-world evidence and further supports the use of IT ziconotide as an important option for the management of chronic pain. IT ziconotide represents a valuable addition to the armamentarium of pain management strategies, offering hope for improved quality of life for patients suffering from chronic, treatment-resistant pain. Continued research and clinical experience will further elucidate its optimal use and role in comprehensive pain care.

RWE ready for reimbursement? A round up of developments in real-world evidence relating to health technology assessment: part 16.

In this update, we discuss recent US FDA guidance offering more specific guidelines on appropriate study design and analysis to support causal inference for non-interventional studies and the launch of the European Medicines Agency(EMA) and the Heads of Medicines Agencies (HMA) public electronic catalogues. We also highlight an article recommending assessing data quality and suitability prior to protocol finalization and a Journal of the American Medical Association-endorsed framework for using causal language when publishing real-world evidence studies. Finally, we explore the potential of large language models to automate the development of health economic models.

Methods of a cluster-randomized, type II hybrid implementation effectiveness trial to prospectively assess extended-duration thromboprophylaxis for at-risk medical patients being discharged to prevent hospital-associated venous thromboembolism

BackgroundVenous thromboembolism (VTE) is the third leading cause of preventable hospital-associated (HA) death. Most HA-VTE, including fatal pulmonary emboli, occur among medically ill patients. The rate of symptomatic VTE more than doubles over the first 21 days after hospital discharge. Trials have demonstrated that the burden of HA-VTE may be reduced with postdischarge thromboprophylaxis; however, few patients receive this therapy. We formerly validated the ability of eVTE (eVTE is the abbreviation for a risk assessment tool constituted by 2 calculations: one predicts 90-day VTE and the other predicts 30-day major bleeding derived from only elements of the complete blood count and basic metabolic panel and age) to identify medical patients being discharged with both an elevated risk of VTE and a low risk of bleeding. ObjectivesImplement a cluster-randomized, stepped wedge, type II hybrid implementation/effectiveness trial generating an alert among select at-risk patients upon discharge for implementation of thrombosis chemoprophylaxis in a 23-hospital not-for-profit healthcare system. MethodsWe use the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework to guide implementation and outcomes reporting. ResultsThe primary outcome for aim 1 (implementation) is the prescription of rivaroxaban 10 mg daily for 30 days as postdischarge thromboprophylaxis among at-risk patients. The primary efficacy and safety outcomes (effectiveness) are the 90-day composite of symptomatic VTE, myocardial infartcion, nonhemorrhagic stroke, all-cause mortality, and 30-day major bleeding. ConclusionThe eVTE trial will provide high-quality, real-world evidence on the effectiveness and safety of a pragmatic intervention to implement targeted postdischarge thromboprophylaxis using decision support embedded in the electronic health record.

Developing PRISM: A Pragmatic Institutional Survey and Bench Marking Tool to Measure Digital Research Maturity of Cancer Centers.

Multicenter precision oncology real-world evidence requires a substantial long-term investment by hospitals to prepare their data and align on common Clinical Research processes and medical definitions. Our team has developed a self-assessment framework to support hospitals and hospital networks to measure their digital maturity and better plan and coordinate those investments. From that framework, we developed PRISM for Cancer Outcomes: PR: agmatic I: nstitutional S: urvey and benchM: arking. The primary objective was to develop PRISM as a tool for self-assessment of digital maturity in oncology hospitals and research networks; a secondary objective was to create an initial benchmarking cohort of >25 hospitals using the tool as input for future development. PRISM is a 25-question semiquantitative self-assessment survey developed iteratively from expert knowledge in oncology real-world study delivery. It covers four digital maturity dimensions: (1) Precision oncology, (2) Clinical digital data, (3) Routine outcomes, and (4) Information governance and delivery. These reflect the four main data types and critical enablers for precision oncology research from routine electronic health records. During piloting with 26 hospitals from 19 European countries, PRISM was found to be easy to use and its semiquantitative questions to be understood in a wide diversity of hospitals. Results within the initial benchmarking cohort aligned well with internal perspectives. We found statistically significant differences in digital maturity, with Precision oncology being the most mature dimension, and Information governance and delivery the least mature. PRISM is a light footprint benchmarking tool to support the planning of large-scale real-world research networks. It can be used to (i) help an individual hospital identify areas most in need of investment and improvement, (ii) help a network of hospitals identify sources of best practice and expertise, and (iii) help research networks plan research. With further testing, policymakers could use PRISM to better plan digital investments around the Cancer Mission and European Digital Health Space.