Real-World Evidence to Reinforce Clinical Trial Evidence in Health Technology Assessment: A Critical Review of Real-World Evidence Requirements from Seven Countries and Recommendations to Improve Acceptance.

BACKGROUND: Real-world evidence (RWE) can reinforce clinical trial evidence in health technology assessment (HTA). OBJECTIVES: Review HTA bodies' (HTAbs) requirements for RWE, real uses, and acceptance across seven countries (Brazil, Canada, France, Germany, Italy, Spain, and the United Kingdom) and outline recommendations that may improve acceptance of RWE in efficacy/effectiveness assessments and appraisals processes. METHODS: RWE requirements were summarized based on HTAbs' guidelines. Acceptance by HTAbs was evaluated based on industry experience and case studies. RESULTS: As of June 2022, RWE methodological guidelines were in place in three of the seven countries. HTAbs typically requested analyses based on local data sources, but the preferred study design and data sources differed. HTAbs had individual submission, assessment, and appraisal processes; some allowed early meetings for the protocol and/or results validation, though few involved external experts or medical societies to provide input to assessment and appraisal. The extent of submission, assessment, and appraisal requirements did not necessarily reflect the degree of acceptance. CONCLUSION: All the countries reviewed face common challenges regarding the use of RWE. Our proposals address the need to facilitate collaboration and communication with industry and regulatory agencies and the need for specific guidelines describing RWE design and criteria of acceptance throughout the assessment and appraisal processes.

The burden of neutropenic sepsis in patients with advanced non-small cell lung cancer treated with single-agent docetaxel: A retrospective study.

OBJECTIVES: To describe rates of confirmed and suspected neutropenic sepsis (NS) and associated hospital resource utilisation in patients with non-small cell lung cancer (NSCLC) treated with docetaxel monotherapy following relapse after ≥1 line of chemotherapy in routine UK clinical practice. MATERIALS AND METHODS: A multi-centre, retrospective, observational research study was conducted in seven centres across England and Wales. Adult patients with stage III/IV NSCLC initiated on docetaxel monotherapy between 2010 and 2016 in routine clinical practice (aged ≥18 years at initiation) following failure of first-line chemotherapy were eligible. Data were collected from hospital medical records between May 2016 and July 2016, on all episodes of confirmed or suspected NS related to docetaxel monotherapy, including patient characteristics. Episodes of confirmed NS were defined as documented absolute neutrophil count <1.0×109/L, plus temperature >38°C or other signs/symptoms of sepsis, otherwise episodes were classified as suspected NS. RESULTS: 121 patients were included (median age 65.5 years; 57.9% male; median 4.0 cycles of docetaxel; 19.8% treated with prophylactic granulocyte-colony stimulating factor). Episodes of confirmed or suspected NS were recorded in 21/121 (17.4%) patients (11 confirmed episodes in 11 [9.1%] patients and 11 suspected episodes in 10 [8.3%] patients). Resource utilisation data were available for 21/22 episodes; the mean length of stay for confirmed NS admissions (n=11) was 9.2 (SD: 9.2) days and for suspected NS admissions (n=10) was 4.7 (SD: 4.6) days. The most commonly prescribed treatment for NS was piperacillin/tazobactam therapy (46.5% of all documented treatments). The mean total costs of managing patients with confirmed NS (n=11) and suspected NS (n=9) were £3163 (SD: £2921) and £1790 (SD: £1585) per patient, respectively. CONCLUSION: Rates of confirmed NS in UK clinical practice were broadly similar to those reported in clinical trials; however, the burden of suspected NS, not routinely reported elsewhere, is also substantial.

The economic burden of complications occurring in major surgical procedures: a systematic review.

OBJECTIVES: On the basis of a systematic review, we aimed to establish the cost and drivers of cost and/or resource use of intra- and perioperative complications occurring as a result of selected major surgical procedures, as well as to understand the relationship between costs and severity of complication and, consequently, the economic burden they represent. We also assessed the clinical and economic methodologies used to derive costs and resource use across the studies with a view to providing guidance on reporting standards for these studies. METHODS: We searched EMBASE, MEDLINE and Econlit (from 2002 to 2012) for study publications including resource use/cost data relating to surgical complications. RESULTS: We identified 38 relevant studies on pancreatic (n = 14), urologic (n = 4), gynaecological (n = 6), thoracic (n = 13) and hepatic surgery (n = 1). All studies showed that complications lead to higher resource use and hospital costs compared with surgical procedures without complications. Costs depend on type of complication and complication severity, and are driven primarily by prolonged hospitalisation. There was considerable heterogeneity between studies with regard to patient populations, outcomes and procedures, as well as a lack of consistency and transparency of reporting of costs/resource use. Complication severity grading systems were used infrequently. CONCLUSIONS: The overall conclusions of included studies are consistent: complications represent an important economic burden for health care providers. We conclude that more accurate and consistent data collection is required to serve as input for good-quality economic analyses, which in turn can inform hospital decisions on cost-efficient allocation of their limited resources.