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In this latest update we highlight the publication of a draft real-world evidence framework by the UK National Institute for Health and Care Excellence, and describe a press release from Germany’s Institute for Quality and Efficiency in HealthCare outlining how real-world evidence submissions are not following their guidelines. We also discuss whether the lack of adherence to guidelines is due to ignorance of these guidelines on the part of manufacturers, the difficulty in achieving best practices or a failure of guidelines to comprehensively describe best practices.

In this latest update we highlight recent publications from the US FDA and a Canadian Health Technology Assessment collaboration which provide insights into the future role of real-world evidence in market access in terms of health technology management.

Aim: To investigate the comparative effectiveness of trastuzumab emtansine (T-DM1) in a real-world population of HER2+ metastatic breast cancer (mBC) patients. Materials & methods: The Flatiron Health database was used to identify a cohort of HER2+ mBC patients who received first-line trastuzumab treatment and T-DM1 or lapatinib plus chemotherapy as second-line treatment. Overall survival was compared between the two groups. Results: A total of 278 patients with HER2+ mBC received second-line T-DM1 and 34 lapatinib plus chemotherapy. Overall survival was longer in patients treated with T-DM1 than those treated with lapatinib plus chemotherapy (adjusted hazard ratio: 0.56; 95% CI: 0.38–0.85). Conclusion: Real-world data supports the effectiveness of T-DM1 in the second-line treatment of HER2+ mBC patients.

In this latest update we highlight a recent International Society of Pharmacoeconomics and Outcomes Research Good Practice Report on machine learning (ML) for health economics and outcomes research. We specifically discuss use cases of ML that offer opportunities in the generation of evidence using real-world data, including improvements in the identification of study cohorts, confounder identification and adjustment and estimating treatment effect heterogeneity. Barriers to the wider adoption of ML methods are also discussed.

Aim: There are different methods to identify chronic kidney disease (CKD) in Clinical Practice Research Datalink (CPRD)-Hospital Episode Statistics (HES). Methods: Using CPRD-HES, nonvalvular atrial fibrillation patients were classified according to CKD category. Results: Using glomerular filtration rate/estimated glomerular filtration rate tests only to identify patients with CKD resulted in 3.5% stage 2, 2.7% stage 3, 0.3% stage 4 and 0.03% stage 5. Using data from diagnostic codes to identify patients with CKD resulted in 1.4% stage 3, 0.4% stage 4 and 0.3% stage 5. Using test records and codes resulted in 3.5% stage 2, 4.0% stage 3, 0.6% stage 4 and 0.4% stage 5. Conclusion: To identify CKD status in CPRD-HES, a combination of test records and codes should be used. Using diagnostic codes only significantly underestimates CKD prevalence.

Aim: The impact of different strategies to handle patients with data recorded under multiple Clinical Practice Research Datalink (CPRD) identifiers (IDs) is unknown. Patients and methods: Six approaches to handling patients appearing under multiple CPRD IDs were defined. The impact of the approaches was illustrated using a case study describing the clinical characteristics of a population of nonvalvular atrial fibrillation patients. Results: 5.6% of patients had more than one CPRD ID. Across all six approaches implemented, no material difference in the characteristics of nonvalvular atrial fibrillation patients were observed. Conclusion: While strategies which longitudinally append patient registration periods under different CPRD IDs maintain independence while using all available data, their implementation had little impact on the results of our case study.

This month we focus on papers that provide insights into the potential for target trial emulation to be used in health technology assessment, the role of real-world evidence (RWE) in informing additional elements of value and the importance of RWE to European joint clinical assessments.

Highlighting the latest developments in both real-world evidence as it relates to health technology assessment and acceptance of real-world evidence by health technology assessment agencies.

In the latest update we focus on recent publications which have provided insights into the importance of focusing on the development and consideration of a body of real-world evidence, and an approach to evaluating the complex area of treatment sequencing.

In this round up, we cover how COVID-19 has been beneficial for improved access to real-world data, as well as how real-world data can be used to address health inequity, an area of increasing interest for health technology assessment.

In this round up, we discuss a number of recent publications that have utilized real-world evidence to explore the value that innovative treatments have brought to patients.

After decades of warfarin being the only oral anticoagulant (OAC) widely available for stroke prevention in atrial fibrillation, four direct OACs (apixaban, dabigatran, edoxaban and rivaroxaban) were approved after demonstrating noninferior efficacy and safety versus warfarin in randomized controlled trials. Comparative effectiveness research of OACs based on real-world data provides complementary information to randomized controlled trials. Propensity score matching and inverse probability of treatment weighting are increasingly popular methods used to address confounding by indication potentially arising in comparative effectiveness research due to a lack of randomization in treatment assignment. This review describes the fundamentals of propensity score matching and inverse probability of treatment weighting, appraises differences between them and presents applied examples to elevate understanding of these methods within the atrial fibrillation field.

Aim: To compare the risk of stroke, systemic thromboembolism and bleeding, in patients initiating apixaban or acenocoumarol for the treatment of nonvalvular atrial fibrillation. Methods: An observational, retrospective study was performed using medical records of patients who initiated apixaban or acenocoumarol between 2015 and 2017. Propensity score matching was used to match patients; stroke, systemic thromboembolism, major and minor bleeding events were compared between the matched patients. Results: Patients who were prescribed apixaban had a lower rate of systemic embolism/stroke (hazard ratio [HR] = 0.54; 95% CI: 0.38–0.78; p = 0.001), minor bleeding (HR = 0.64; 95% CI: 0.52–0.79; p Conclusion: Patients prescribed apixaban for the treatment of nonvalvular atrial fibrillation had lower rates of thromboembolic events and minor/major bleeding than patients on acenocoumarol.

Aim: Nonvalvular atrial fibrillation (NVAF) requires long-term anticoagulation treatment, which may necessitate frequent primary care visits. Materials & methods: NVAF patients initiating warfarin or apixaban in 2012–2017 were identified from linked primary (Clinical Practice Research Datalink) and secondary care (Hospital Episode Statistics) data. A propensity score matched Cox regression model compared discontinuation risk. Primary care visits were compared via negative binomial regression. Results: A total of 2695 apixaban users were matched to warfarin patients. Discontinuation risk was lower with apixaban than warfarin (hazard ratio: 0.40; 95% CI: 0.35–0.46). Apixaban patients averaged 12.2 annual primary care visits, versus 17.1 for warfarin users (p Conclusion: Apixaban was associated with reduced rates of discontinuation and primary care visits compared with warfarin.

Aim: This study aimed to evaluate the risk of major bleeding among two cohorts of nonvalvular atrial fibrillation patients newly initiating a vitamin K antagonist (VKA) or apixaban in a real-world setting in Italy. Patients & methods: A retrospective study using a large administrative database of Italian local health units was performed, using data from ten local health units and patients were included from the date of new initiation of apixaban or VKAs from January 2012 to June 2015. Results: Risk of major bleeding was calculated using an adjusted Cox regression model. Compared with VKA, apixaban had a significantly lower risk of major bleeding (hazard ratio = 0.44 [95% CI: 0.12–0.97]). Conclusion: In this analysis, apixaban was associated with a lower risk of major bleeding compared with VKA.

Comparative effectiveness research (CER) guidelines have been developed to direct the field toward the most rigorous study methodologies. A challenge, however, is how to ensure the best evidence is generated, and how to translate methodologically complex or nuanced CER findings into usable medical evidence. To reach that goal, it is important that both researchers and end users of CER output become knowledgeable about the elements that impact the quality and interpretability of CER. This paper distilled guidance on CER into a practical tool to assist both researchers and nonexperts with the critical review and interpretation of CER, with a focus on issues particularly relevant to CER in oncology.