Drugs: Late Stage Clinical Development
Late-stage clinical development primarily aims at demonstrating efficacy, safety, and cost-effectiveness. It corresponds to Phases 2b and 3 confirmatory studies. The product is tested in larger clinical studies, often as compared with the therapeutic ‘gold standard’ or standard-of-care (SoC), if any. The collection of safety data on a larger scale enables the confirmation of the product’s safety profile.
Phase 3 trials are conducted in a large number of countries in view of supporting approval in broader markets. Health economics data are also gathered to demonstrate the product’s value to payers and support post-approval reimbursement.
Upcoming developments are initiated in parallel to late-stage clinical testing. Early access programs (US expanded access / EU compassionate use) provide an initial commercial opportunity to facilitate clinician experience and early product awareness. Manufacturing is often transferred to larger facilities to prepare for commercial-scale production. Dialogue with regulators and payers intensifies, both on ongoing clinical trials as well as on upcoming registration and launch. Clinical and economic data are packaged in a value proposition that is tested with payers (endpoints, target population, choice of comparators, patient outcomes) in preparation for reimbursement applications.
Key challenges encompass:
- How to obtain endorsement from regulators on the late-stage clinical development strategy?
- How to articulate a development plan across multiple regions, with potentially different requirements?
- How to confirm/improve the products benefit/risk ratio?
- Which clinical endpoints would address both regulators' and payers' requirements?
- How to validate manufacturing processes and methods?
- How to design/ adapt manufacturing for commercial launch (upscaling)?
- Which data will the payers require?
- Develop essential documents (protocol, IND/IMPD, IB, consent forms)
- Assemble and submit IND/CTA packages tailored to local requirements, obtain approval from regulatory authorities to conduct studies (coordinate international regulatory processes)
- Oversee execution and ensure regulatory compliance of clinical trials (protocol, IB amendments)
- Manage and report safety cases (expedited & periodic reporting)
- Monitor product safety profile, organize DSMBs or clinical expert panels
- Draft development risk management plan
- Anticipate the adaptation of the clinical safety system and database to a post-marketing pharmacovigilance setting
- Assess opportunities to generate pre-NDA/BLA/MAA awareness and, potentially, revenue
- Design and implement named-patient or cohort expanded access /compassionate use programs (design protocols for therapeutic use, obtain approval from regulatory authorities, ensure product distribution, fulfill safety reporting obligations)