A national evaluation analysis and expert interview study of real-world data sources for research and healthcare decision-making.

Real-world data (RWD) can provide intel (real-world evidence, RWE) for research and development, as well as policy and regulatory decision-making along the full spectrum of health care. Despite calls from global regulators for international collaborations to integrate RWE into regulatory decision-making and to bridge knowledge gaps, some challenges remain. In this work, we performed an evaluation of Austrian RWD sources using a multilateral query approach, crosschecked against previously published RWD criteria and conducted direct interviews with representative RWD source samples. This article provides an overview of 73 out of 104 RWD sources in a national legislative setting where major attempts are made to enable secondary use of RWD (e.g. law on the organisation of research, "Forschungsorganisationsgesetz"). We were able to detect omnipresent challenges associated with data silos, variable standardisation efforts and governance issues. Our findings suggest a strong need for a national health data strategy and data governance framework, which should inform researchers, as well as policy- and decision-makers, to improve RWD-based research in the healthcare sector to ultimately support actual regulatory decision-making and provide strategic information for governmental health data policies.

Quality Criteria for Real-world Data in Pharmaceutical Research and Health Care Decision-making: Austrian Expert Consensus.

Real-world data (RWD) collected in routine health care processes and transformed to real-world evidence have become increasingly interesting within the research and medical communities to enhance medical research and support regulatory decision-making. Despite numerous European initiatives, there is still no cross-border consensus or guideline determining which qualities RWD must meet in order to be acceptable for decision-making within regulatory or routine clinical decision support. In the absence of guidelines defining the quality standards for RWD, an overview and first recommendations for quality criteria for RWD in pharmaceutical research and health care decision-making is needed in Austria. An Austrian multistakeholder expert group led by Gesellschaft für Pharmazeutische Medizin (Austrian Society for Pharmaceutical Medicine) met regularly; reviewed and discussed guidelines, frameworks, use cases, or viewpoints; and agreed unanimously on a set of quality criteria for RWD. This consensus statement was derived from the quality criteria for RWD to be used more effectively for medical research purposes beyond the registry-based studies discussed in the European Medicines Agency guideline for registry-based studies. This paper summarizes the recommendations for the quality criteria of RWD, which represents a minimum set of requirements. In order to future-proof registry-based studies, RWD should follow high-quality standards and be subjected to the quality assurance measures needed to underpin data quality. Furthermore, specific RWD quality aspects for individual use cases (eg, medical or pharmacoeconomic research), market authorization processes, or postmarket authorization phases have yet to be elaborated.

Economic impact of industry-sponsored clinical trials of pharmaceutical products in Austria.

Aims: Modern pharmaceutical product development is a long and complex process associated with significant investments by pharmaceutical companies. The innovative pharmaceutical industry accounts for the vast majority of expenditures in clinical trials of potential new pharmaceuticals and therefore generates economic activity within a country. The aim was to assess the far-reaching economic impact of industry-sponsored clinical-trials (ISCTs) of pharmaceutical products for the healthcare system and the national economy.Materials and methods: The study approach was based on three analytical steps. First, a survey among 15 pharmaceutical companies in Austria was conducted to evaluate the annual number of ISCTs subdivided according to trial phase, therapeutic areas and associated employees. Second, the monetary value of treatments performed in ISCTs was calculated based on a sample of clinical-trial protocols. Finally, the macroeconomic impact, measured in terms of value-added and jobs created by the conducted ISCTs, was calculated using Input-Output analysis by applying an extended Leontief-model.Results: The study demonstrated that €116.22 million spent in ISCTs generated a total value added of €144 million, €74 million direct, in 2018. Each year a medical treatment value of €100 million was financed through 463 ISCTs, with an average value of medical treatment of €37,068 per recruited patient. This represents a significant 0.3% of annual current health-expenditures. In summary, each Euro invested by the pharmaceutical industry in ISCTs generates €1.95 for the Austrian economy. ISCTs also created and secured employment in the extent of 2,021 full-time-equivalents, thus resulting in an employment multiplier of 1.66.Conclusions: In conclusion, conducting clinical-trials by pharmaceutical industry-beside its importance in its own domain-results in tangible benefits and a positive macroeconomic impact that contribute to the sustainability of the Austrian healthcare system by complementing its limited resources. Furthermore, it is a non-negligible factor in locational and industrial policy.

Phase Ib trial combining capecitabine, erlotinib and bevacizumab in pancreatic adenocarcinoma - REBECA trial.

Background Purpose of this phase Ib trial was to establish the maximum tolerable dose (MTD) of capecitabine and to escalate the dosages of erlotinib and bevacizumab to determine the recommended phase II dose (RP2D) in patients with advanced/metastatic pancreatic adenocarcinoma not pretreated for metastatic disease. Methods Starting doses were capecitabine 500 mg/m2 bid orally continuously, erlotinib 100 mg orally daily, and bevacizumab 5 mg/kg intravenously q 2 weeks. Dose escalation was performed according to a 3 + 3 design for capecitabine until MTD, for erlotinib and bevacizumab until the maximum doses registered by applying a substance-related, toxicity-based scheme accompanied by pharmacokinetic analysis. Circulating tumor cells (CTCs) were determined pretherapeutically by immunohistochemical identification after enrichment with immunomagnetic separation. Results Thirty patients were evaluable at six dose levels. 900 mg/m2 bid were determined as MTD for capecitabine based on dose-limiting toxicities: cutaneous in two patients and vascular in another. The most severe (Grade (G)3/4) drug-related treatment-emergent adverse events (toxicities) belonged to the categories gastrointestinal, vascular, cutaneous, cardiovascular, metabolic/nutritional or hematological. G3 toxicities occurred in 14 (47%), G3 + G4 in a single (3%) patient. 2 out of 28 patients (7%) exerted partial response, 17 (61%) stable disease. Pharmacokinetic evaluation revealed lack of drug-drug interaction between capecitabine and erlotinib and their metabolites. Presence of CTCs was associated with shorter progression-free survival (p = 0.009). Conclusions The study met the primary objective. RP2D was capecitabine 800 mg/m2 bid continuously, erlotinib 150 mg daily, and bevacizumab 10 mg/kg q 2 weeks. The regimen could be applied safely, but demonstrated limited efficacy.

Treatment of osteoporosis with parathyroid hormone and teriparatide.

Nowadays osteoporosis treatment is based primarily on therapy with antiresorptive agents, like the bisphosphonates. Parathyroid hormone (Preotact) and human recombinant parathyroid hormone peptide 1-34 (Teriparatide) are relatively new for the treatment of osteoporosis and belong to the group of anabolic agents. Both agents demonstrated an increase in bone mineral density and a significant reduction in vertebral fractures in postmenopausal women with osteoporosis when given for 18-24 months. Data on nonvertebral fractures are, however, not clear-cut, and so far only bisphosphonates and strontium ranelate have been demonstrated to reduce all types of fractures and therefore remain the front-line option for treatment of osteoporosis. As the safety, tolerability, and cost of the therapy also influence the choice of therapy, Preotact and Teriparatide might be useful additions to the armamentarium for (second-line) treatment of osteoporosis.