The present study confirms that Canadian oncologists are willing to participate in clinical research, but face multiple barriers to trial participation. Those barriers could be mitigated by the implementation of several interventions identified in the study.

Background A significant barrier to conducting clinical trials is their high cost, which is driven primarily by the time and resources required to activate trials and reach accrual targets. The high cost of running trials has a substantial impact on their long-term feasibility and the type of clinical research undertaken. Methods A scoping review of the empirical literature on the costs associated with conducting clinical trials was undertaken for the years 2001–2015. Five reference databases were consulted to elicit how trials costs are presented in the literature. A review instrument was developed to extract the content of in-scope papers. Findings were characterized by date and place of publication, clinical disease area, and network/cooperative group designation, when specified. Costs were captured and grouped by patient accrual and management, infrastructure, and the opportunity costs associated with industry funding for trials research. Cost impacts on translational research and health systems were also captured, as were recommendations to reduce trial expenditures. Since articles often cited multiple costs, multiple cost coding was used during data extraction to capture the range and frequency of costs. Results A total of 288 empirical articles were included. The distribution of reported costs was: patient management and accrual costs (132 articles), infrastructure costs (118 articles) and the opportunity costs of industry sponsorship (72 articles). 221 articles reported on the impact of undertaking costly trials on translational research and health systems; of these, the most frequently reported consequences were to research integrity (52% of articles), research capacity (36% of articles) and running low-value trials (34% of articles). 254 articles provided recommendations to reduce trial costs; of these, the most frequently reported recommendations related to improvements in: operational efficiencies (33% of articles); patient accrual (24% of articles); funding for trials and transparency in trials reporting (18% of articles, each). Conclusion Key findings from the review are: 1) delayed trial activation has costs to budgets and research; 2) poor accrual leads to low-value trials and wasted resources; 3) the pharmaceutical industry can be a pragmatic, if problematic, partner in clinical research; 4) organizational know-how and successful research collaboration are benefits of network/cooperative groups; and 5) there are spillover benefits of clinical trials to healthcare systems, including better health outcomes, enhanced research capacity, and drug cost avoidance. There is a need for more economic evaluations of the benefits of clinical research, such as health system use (or avoidance) and health outcomes in cities and health authorities with institutions that conduct clinical research, to demonstrate the affordability of clinical trials, despite their high cost.

Background: Contract negotiations between academic sites and pharmaceutical companies, which often include contentious issues such as publication rights and indemnification, are perceived to be delaying the initiation of clinical research to the detriment of academic sites and patients. Given the need to improve the contract process in Ontario, the Council of Academic Hospitals of Ontario (CAHO) led an initiative that developed a set of standard principles that Ontario hospitals are recommended to follow when negotiating clinical trial agreements with industry sponsors. Methods: A committee comprising members from academic hospitals and organizations across Ontario was formed. This CAHO Steering Committee on Harmonizing Clinical Trial Agreements set up a working group to draft a principles document based largely on preexisting principles. The draft principles went through several iterations of review and revision by the committee and by the member hospitals. A mechanism to ensure keeping it a live and up-to-date document was developed. Results: The initial hope of the committee was to develop a standard clinical trial agreement for use by all sites and all companies; however, the committee felt that this was unlikely given the diverse interests and head offices of the pharmaceutical companies. As such the committee developed a standard set of principles to be used for contract negotiation; this document started with a superior set of principles, and then addressed a number of issues including publication rights, intellectual property issues, confidentiality, privacy, and indemnification. This document is currently being used widely by Ontario hospitals, and may be useful for other jurisdictions. Interpretation: Publication of the standards for clinical trial agreements increases consistency in the standards applied by teaching hospitals and allows companies to develop or refine their templates to address the principles thought to be important by all Ontario teaching hospitals. Company templates that are in line with these principles are expected to require far less negotiation, if any at all.

219 Background: The 2011 Canadian Cancer Research Alliance (CCRA) report on the State of Cancer Clinical Trials in Canada outlined in detail the threats to the conduct of academic oncology clinical trials caused by increasing complexity and workload resulting from a perceived onerous regulatory environment. The report recommended engaging Health Canada and key stakeholders to foster agreement in appropriate interpretations of the Canadian Food and Drug Regulations Part C Division 5 and ICH Good Clinical Practice (GCP) guidelines. Methods: The ISCT Working Group (ISCT WG) was formed in 2012 to address the CCRA recommendations for academic clinical trials and include experts from multiple therapeutic areas. The primary objective of the ISCT is to develop specific, practical interpretations of current regulations, laws and guidelines to facilitate Canadian clinical trials. Feedback was obtained from interested parties and ISCT members by means of surveys, face-to-face meetings and conference calls. Results: The major areas of concern identified include Health Canada Clinical Trial Applications, Investigational Product supply, monitoring, oversight of equipment and facilities, delegation of duties, validation of electronic systems, source documents and records retention, trial costs, the consistency of interpretation by different divisions of Health Canada, and access to related resources. A subcommittee was established for each area identified above and a series of recommendations to streamline processes with a focus to reduce regulatory burden for academic clinical trials. The ISCT WG used other relevant documents including the OECD framework and FDA Guidance on Risk Based Monitoring to inform its work. Conclusions: The final recommendations of the ISCT have been provided to all stakeholders, presented at international conferences and published on the N2 website. Canadian academic sites have used guidelines during Health Canada inspections with success. Future goals include an ISCT Workshop for academic site leaders to facilitate implementation of the ISCT guidelines, continue to address areas of concern, and track the success of the recommendations in ameliorating the conduct of academic trials.