Advancing the use of real world evidence in health technology assessment: insights from a multi-stakeholder workshop.

Introduction: Real-world evidence (RWE) in health technology assessment (HTA) holds significant potential for informing healthcare decision-making. A multistakeholder workshop was organised by the European Health Data and Evidence Network (EHDEN) and the GetReal Institute to explore the status, challenges, and opportunities in incorporating RWE into HTA, with a focus on learning from regulatory initiatives such as the European Medicines Agency (EMA) Data Analysis and Real World Interrogation Network (DARWIN EU®). Methods: The workshop gathered key stakeholders from regulatory agencies, HTA organizations, academia, and industry for three panel discussions on RWE and HTA integration. Insights and recommendations were collected through panel discussions and audience polls. The workshop outcomes were reviewed by authors to identify key themes, challenges, and recommendations. Results: The workshop discussions revealed several important findings relating to the use of RWE in HTA. Compared with regulatory processes, its adoption in HTA to date has been slow. Barriers include limited trust in RWE, data quality concerns, and uncertainty about best practices. Facilitators include multidisciplinary training, educational initiatives, and stakeholder collaboration, which could be facilitated by initiatives like EHDEN and the GetReal Institute. Demonstrating the impact of "driver projects" could promote RWE adoption in HTA. Conclusion: To enhance the integration of RWE in HTA, it is crucial to address known barriers through comprehensive training, stakeholder collaboration, and impactful exemplar research projects. By upskilling users and beneficiaries of RWE and those that generate it, promoting collaboration, and conducting "driver projects," can strengthen the HTA evidence base for more informed healthcare decisions.

Measuring the Effectiveness of Real-World Evidence to Ensure Appropriate Impact.

The value of real-world evidence (RWE) in medicines regulation and health technology assessment has been increasingly emphasized. Nevertheless, although RWE is increasingly used, there has been limited systematic evidence of its value. A recent study that examined the role and impact of RWE in regulatory assessments conducted through the European Medicines Agency provided such evidence. Results of the study demonstrated RWE was important to decision making, particularly for certain questions such as the quantification of adverse events, the evaluation of risk minimization measures, and the assessment of product usage. The study suggested, however, that in many of the assessments further RWE would have been valuable and concluded that RWE has, as yet, played a limited role in hypothesis generation and in the assessment of medication effectiveness. This study had been possible only because of the transparency of the European Medicines Agency decision making. Ensuring transparency of RWE evidence collection, study design and conduct, and of decision making based on this evidence will facilitate further development of the uses and value of RWE. Keywords: benefit-risk assessment; medicines regulation; real-world evidence; regulatory decision making.

Management of poor grade sub-arachnoid haemorrhage - clinical judgement v/s a formal model.

OBJECTIVE: The poor grade subarachnoid haemorrhage patients represent a unique cohort with lack of clear treatment protocol. Most neurosurgical units in the UK will manage them at local hospital until they make a significant recovery, this period can put them at higher risk of rebleed while with aggressive treatment a significant subset can achieve a favourable outcome. Identification of this subset is difficult and decision to treat them is associated with significant commitment of neurosurgical and ITU resources. Recent paper by Szklener has come up with a scale for prognostication in this subgroup of patients. We wanted to check the validity of this scale in our patient population and see if this scale can be used to guide early patient transfer and aggressive management at the Neurosurgical unit. METHODS: We retrospectively reviewed our referral database for all poor grade subarachnoid patients referred over 2 years. Demographic information, Fisher and WFNS scores, admitting leucocyte count and outcome information as per MRS were obtained. These were scored as per the scale suggested by Szklener. RESULTS: A total of 115 poor grade subarachnoid patients were referred over the study time frame. 47 of them were accepted for admission . 18/47 patients achieved a favourable outcome (GOS4-5). Only 1 patient managed in peripheral hospital had a good outcome. There was a significant association between Szklener's score and achieving a favourable outcome p = 0.002. CONCLUSION: A selective admission policy could work specially with current economic climate, achieving outcomes comparable to admit-all. However, to optimise outcomes for all patients an aggressive standardised management at peripheral hospitals and a uniform admission policy assisted by Szklener score may be adopted. Szklener's model predicts the outcome better than WFNS and age but more validation is needed.

Making sense of big data in health research: Towards an EU action plan.

Medicine and healthcare are undergoing profound changes. Whole-genome sequencing and high-resolution imaging technologies are key drivers of this rapid and crucial transformation. Technological innovation combined with automation and miniaturization has triggered an explosion in data production that will soon reach exabyte proportions. How are we going to deal with this exponential increase in data production? The potential of "big data" for improving health is enormous but, at the same time, we face a wide range of challenges to overcome urgently. Europe is very proud of its cultural diversity; however, exploitation of the data made available through advances in genomic medicine, imaging, and a wide range of mobile health applications or connected devices is hampered by numerous historical, technical, legal, and political barriers. European health systems and databases are diverse and fragmented. There is a lack of harmonization of data formats, processing, analysis, and data transfer, which leads to incompatibilities and lost opportunities. Legal frameworks for data sharing are evolving. Clinicians, researchers, and citizens need improved methods, tools, and training to generate, analyze, and query data effectively. Addressing these barriers will contribute to creating the European Single Market for health, which will improve health and healthcare for all Europeans.

Prognostic Factors in Lobar World Health Organization Grade II Astrocytomas.

BACKGROUND: World Health Organization grade II astrocytomas (AII) are the commonest low-grade glioma subset, but their prognostic factors are subject to debate. This institutional study aimed to identify prognostic factors in lobar AII. METHODS: Retrospective review of newly diagnosed, lobar AII between 2006 and 2012. Patient demographics, imaging, and treatment data were obtained. Isocitrate dehydrogenase-1 (IDH1) status was assessed via immunohistochemistry. Multivariate analysis was performed with Cox regression to identify prognostic factors for overall survival (OS) and progression-free survival (PFS). RESULTS: A total of 92 adult patients were identified with a median age of 42 years (range 20-73 years) and median follow-up period of 45 months (range, 7-98 months). Seizures were the commonest mode of presentation (75%). IDH1 immunopositivity was seen in 46 of 83 patients (55%). Radiology diagnosis agreed with histology in 76% of cases, and 28% of tumors had documented evidence of some degree of contrast enhancement. Surgical management was either resection (51%) or biopsy (49%) and postoperative radiotherapy was used in patients with unfavorable prognostic features. The median OS and PFS were 85 months (range 2-98 months) and 36 months (95% confidence interval [95% CI] 27-45 months), respectively. Surgical resection (P < 0.001; hazard ratio [HR] 5.072; 95% CI 2.050-12.550), absence of contrast enhancement (P = 0.006; HR 3.180; 95% CI 1.403-7.206), and IDH1 immunopositivity (P = 0.006; HR 3.310; 95% CI 1.416-7.738) were associated with improved OS. Good performance status (P = 0.005; HR 5.965; 95% CI 1.710-20.804) and absence of contrast enhancement (P < 0.001; HR 3.446; 95% CI 1.883-6.304) were associated with improved PFS. CONCLUSIONS: Patients with World Health Organization grade II astrocytomas have better overall survival if their tumor is nonenhancing, amenable to surgical resection, and exhibits the IDH1 mutation. These factors should be used to guide patient management and inform prognosis.

Diagnostic challenges, management and outcomes of midline low-grade gliomas.

INTRODUCTION: Low-grade gliomas (LGGs) are slow-growing and diffusely infiltrating tumours constituting 25-30 % of adult gliomas. Rarely, these tumours may arise in the cerebral midline, including the thalamus, hypothalamus, tectum and brainstem. Here we present a contemporary experience with midline LGGs. METHODS: Midline LGGs were identified from a retrospective database of adult patients who received a histological diagnosis of WHO grade II glioma between 2006 and 2012 at a single institution. Location, radiological data and clinical outcomes were collected. IDH1 status was assessed by immunohistochemistry. RESULTS: Eighteen patients with midline LGGs were identified, with a median age of 45. Most received biopsy upon diagnosis, though asymptomatic patients with tectal tumours underwent active surveillance. Oligodendroglial tumours were much less common than in a comparable group of lobar tumours (6 vs. 38 %, Fisher's exact test, p = 0.007). Only one tumour was immunopositive for IDH1 (1/17). Radiological diagnosis correlated with histology in only 71 % of patients. Median survival of midline LGGs was 48 months (3-90 months) and radiological features such as contrast enhancement, size and radiological diagnosis did not predict survival in this cohort. Median overall survival of midline LGGs was less than lobar LGGs (log-rank, p = 0.006), though differences became insignificant when considering only biopsied astrocytomas in both locations (log-rank, p = 0.491). CONCLUSIONS: Diagnosis of midline LGGs is complicated by both limitations of biopsy and imaging. Midline tumours have a poorer prognosis compared to lobar equivalents and survival differences are probably due to the absence of significant surgical intervention in midline locations.