Key considerations for outsourcing late phase clinical research Alan Nelson (on behalf of Van Zyl Engelbrecht) Senior Project Director at UBC: An Express Script Company
Layout of presentation My presentation is divided into two sections. 1. The landscape today for late phase research. 2. Key considerations for successfully outsourcing late phase clinical research studies.
Landscape today Cost of clinical development is increasing: On average, requires in excess of $1.2b for a NCE to reach the market(?) Manufacturers need to maximise their return on investment in developing new products: Globalisation: the market for products grows as manufacturers expand into new markets and therapeutic areas. This set against a changing regulatory environment
Landscape today Increased expectations from Regulatory Agencies on manufacturers (manufacturers needing to protect their investment ) Ongoing post marketing safety surveillance Improved risk benefit (efficacy & compliance) Increased scrutiny by payers and for manufactures to show added value in a Real World setting Improved cost effectiveness profiles Set against an environment where Late Phase Expertise and local knowledge largely now represented within CRO sector
Key considerations for outsourcing Late Phase studies Key considerations for pharmaceutical companies to effectively outsource and meet these requirements for late phase research data. 1. Determine the type of late phase study 2. Implementation considerations 3. Select the right partners
Key considerations: 1) Type of late phase study Interventional studies Prospective design mostly, involving an interventional design (patients randomised or require specified diagnostic tests). More well defined regulatory environment. e.g. Clinical Trials, or randomised Phase IV comparator studies Non-interventional (or observational) studies Prospective or retrospective involving an observational design striving to measure real world clinical, economic and/or safety outcomes. Less defined regulatory environment. e.g. Product/ Disease Registries, Chart Review Studies, Time and Motion Studies
Type of late phase study (cont.) Interventional Study Investigational research drug or additional procedures are given/ take place Protocol dictate who receive IMP + what additional procedures take place Harmonised regulatory environment (ICH GCP) Experience researchers Non-Interventional Study Any treatments used as per SmPC and patients are simply following normal care practices Protocol does not dictate what treatment or tests patients will receive Regulatory environment not harmonised Research naive participating sites Methodology defines the type of study and not the scientific objective.
Type of late phase study (cont.) Regulatory and implementation implications Type of late phase study is critical as that will determine the regulatory requirements for the study. What and Where decides the How. What? Prospective study? Retrospective study? Mandated study? Tissue collection? Tissue storage / bio-banking? Genetic analysis? Secondary use of data or tissues? Off label use? Where? Which countries and regions within countries? How? Different submission procedures depending on where. Only notifications? Registration required and to who? Approval required and from who? Insurance requirements? Is patient consent required?
Key considerations: 2) Implementation considerations a. Comprehensive strategic view for late phase studies b. Regulatory environment c. Data collection and quality
Implementation considerations (cont.) a. Comprehensive strategic view of late phase trials Who leads late phase studies? - Research and Development or Clinical Operations Do they have the expertise or resource requirement? - Medical Affairs Can increase profile of a study, and be useful points of escalation by Clinical Operations team - Marketing Must remain objective and not use the study for commercial reasons Each is likely to have their own goals, but a successful partnership is likely to involve all the above for successful study execution
Implementation considerations (cont.) b. Regulatory environment Identify the most appropriate regulatory expert (internal or partnership) to support your study submission. Good local knowledge is essential. Determine how your study will be defined in your target markets. Consider factors as the need to capture off-label use, or request potentially supply discounted product after launch. There are many trapdoors to fall down..
Implementation considerations (cont.) b. Regulatory environment Regulatory environment is not harmonised and will remain a significant challenge for the near future. e.g. some MAH may not agree with the requirements set out CHMP ( / EMA) as part of the Marketing Authorisation Seek early involvement of late phase experts in study and protocol design.
Implementation considerations (cont.) c. Data collection and quality Challenges Late phase studies often require large no. s of patients at research naive sites. Wide geographic spread of sites and language / cultural barriers Reduced monitoring frequency potentially jeopardising data quality Study s may be lengthy, and site & patient motivation and retention can be a challenge Solutions: Streamlined document collection and as needed minimal data collection Respect cultural differences and provide flexible solutions. Thorough site qualification and selection process Remote data monitoring and site management Create user friendly kits and tools to keep the study top of mind
Key Considerations: 3) Right partners The right partner(s) is a critical factor to ensure your study is appropriately designed and you can successfully navigate the changing regulatory and data requirements. Key considerations for you and your partner (internal or external) - Partner(s): Regional resource, relevant study experience and local knowledge - You: Ability to manage and contribute to partnership(s) constructively and continuously Be clear on what you need Remember, it s a team effort, and we all share the same goals.
Right partners (cont.) Key Considerations: If you are outsourcing to a CRO, meet the team you plan to use (Bid Defence Meeting) Assess the strength of their proposed study leadership team Is there a good chemistry within their team, and with your team? Timing of the meeting is important..the team you see should be the team you get Get the buy-in of all stakeholders Establish an effective Governance structure A PARTNERSHIP IS A MUTUAL ARRANGEMENT
Right partners (cont.) The right partner(s), key capabilities - must have knowledge and experience regarding the diverse design of late phase studies, and knowledge of how to implement them at the global and local levels - must have a management team and governance structure that you can trust in IT S ALL ABOUT TEAM WORK
Late phase clinical research studies: In summary Last thought regarding late phase research environment Phase I to III Phase IV
Questions?