Development of ‘Core Outcome Sets’ for meningioma in clinical studies: The COSMIC project

Aims To date, meningioma clinical trial activity has been limited, but a number of high-quality studies are underway, with more in development. There is heterogeneity in the outcomes reported in meningioma clinical trials. The COSMIC Project will develop two ‘Core Outcome Sets’ (COS) through comprehensive, transparent, consensus methodology; to ensure outcomes relevant to key stakeholders are reported within and across future meningioma clinical studies. The first will be for use in clinical effectiveness trials (COSMIC: Intervention), the second will be for use in clinical studies of incidental meningioma (COSMIC: Observation). Method Three systematic literature reviews will be performed to generate a long-list of outcomes potentially relevant to meningioma patients, healthcare professionals, researchers, and other stakeholder groups. The first systematic review will present the outcomes reported in published and ongoing meningioma clinical effectiveness trials. The second systematic review will present patient-reported outcomes (PRO) from the measurement tools utilised in meningioma PRO studies. The third systematic review will present the outcomes reported in published and ongoing clinical studies of untreated meningioma. Outcomes will be deduplicated, unique outcomes categorised according to the taxonomy presented by COMET, and the lists combined. The long-list of outcomes will be prioritised through two, 2-round, modified eDelphi surveys including meningioma patients, healthcare professionals, researchers, and other stakeholder groups. Undecided outcomes from both eDelphi surveys will be ratified at two, one-day consensus meeting, with representation from all key stakeholder groups. Results We have formed a study advisory group with international representation from key organisations. The project already has confirmed support from the International Consortium on Meningioma (ICOM), the European Association of Neuro-Oncology (EANO), the Response Assessment in Neuro-Oncology Patient-Reported Outcome group (RANO-PRO), the Society for Neuro-Oncology (SNO), British Neuro-Oncology Society (BNOS), Society of British Neurological Surgeons (SBNS), The Brain Tumour Charity (TBTC), and Brainstrust. Conclusion Standardising minimum outcome reporting in meningioma clinical effectiveness trials and meningioma clinical studies, through the development of these two COS will ensure outcomes reported are relevant to key stakeholder groups, including patients, whilst reducing research waste for a disease with increasing clinical trial activity. We seek to raise awareness of this project and invite participation from a wide range of stakeholders to ensure that the final COS reflects the opinion of the neuro-oncology community. Registration will take place via the study website www.thecosmicproject.org between June-August 2021.

924The landscape of clinical trial activity focusing on Indigenous health in Australia from 2008-2018

Background There are major health disparities between Indigenous and non-Indigenous Australians. To address this, it is vital to understand the landscape of Indigenous trial activity. Methods We extracted data from all Australian trials registered between 2008-2018 on the Australian New Zealand Clinical Trials Registry or ClinicalTrials.gov. Indigenous-focused trials were identified by searching for relevant terms such as ‘Indigenous’ and ‘Aboriginal’. Indigenous versus non-Indigenous trials and Australian trials overall were compared by conditions studied, intervention type, study design and funding. Results Of the 9206 included trials, 139 (1.5%) focused on Indigenous health, and these were mostly in ‘Public Health’ (n = 69, 50%), ‘Mental Health’ (n = 35, 25%) and ‘Cardiovascular’ (n = 25, 18%) (Figure). Compared to other Australian trials, Indigenous trials more frequently studied ear conditions (OR 16.47, 95%CI=8.43-29.99) and public health (OR 4.87, 95%CI=3.65-6.41), and were more likely to focus on screening (OR 3.57, 95%CI=2.10-5.70) and prevention (OR 2.24, 95%CI=1.61-3.08) rather than treatment (OR 0.40, 95%CI =0.30-0.52). They were less likely to be blinded (OR 1.72, 95%CI=1.20-2.49), or have any industry involvement (OR 2.52, 95%CI=1.54-4.43). Conclusions Indigenous trials differed from other Australian trials in health conditions studied, intervention focus, blinding and industry involvement. Relative to population size and burden of disease, the number of trials focusing on Indigenous health is low. Key messages Trial registries can be used to explore whether research appropriately addresses diverse populations such as Indigenous Australians. This can inform future research prioritisation.

A Database of Drug Repurposing Clinical Trials in Oncology

Drug repurposing is an expanding field in medicine but to date there has been little analysis on the degree of clinical trial activity in oncological repurposing. Such analysis is hampered by the lack of a single unified source of clinical trial data. Utilising publicly available registry data, we report on the construction of an online database of clinical trials assessing the use of licensed non-cancer drugs as therapeutic agents against cancer. We outline the methodology for the construction and maintenance of the database, called the ReDO_Trials_DB (https://www.anticancerfund.org/en/redo-trials-db). Summary statistics are reported and also discussion of the research questions arising from the data.

The Disclosure Decision of Foreign Clinical Trials in China: Moderating Effects of Firms’ Contingencies

Result disclosure of clinical trial posts a conflicting logic between private secrecy and public interest. Despite ethical and legal requirements for disclosing clinical trial results, clinical trials’ sponsors tend to withhold the results. We explored the location, timing, and rationale behind the withheld clinical trial results. Based on the entrepreneurial orientation (EO) perspective, we propose that organizational EO contingencies moderate the disclosure decision. We used the completed clinical trial projects in China by foreign and domestic sponsors. First, we found that a unit increase in the sponsor’s experience can increase the disclosure about 1.01 times. Second, we found that industrial enterprises disclose results about 3.7 times more than universities do. Third, we found that foreign clinical trial projects in China tend to disclose 3.9 times more than domestic projects. We link these findings to two types of audience. First, we inform the academic community on the theory and empirics regarding risk-taking behavior in the biopharmaceutical industry’s clinical trial activity. Second, we address the general audiences concerned about the ethical and socioeconomic wellbeing of the public.

Medicines development in the Asia Pacific region

The Asia Pacific region is an extremely diverse region, characterized by heterogeneity from a number of aspects, including culture, religion, economics, landscapes, and languages. This also applies to the standard of medical care and the regulatory requirements for approval of drugs in the region. Developed economies such as Japan and Australia have requirements which are not dissimilar to those of the EU and USA, but still have their own unique requirements. The developing economies all have their own requirements. In the ASEAN region there is harmonization of the dossier format, but each country still has local requirements. The region has seen significant growth in clinical trial activity, both to satisfy local registration and safety requirements and to help accelerate global trial patient recruitment. There is a clear need for training in all aspects of medical, regulatory, clinical and safety aspects of medicines development, which is being addressed through several organizations and at different locations in the region.