How To Design A Clinical Trial Protocol With Patient And FDA Collaboration
By Clinical Leader Editorial Staff
In a recent Clinical Leader Live! episode hosted by Life Science Leader Chief Editor Ben Comer, clinical trial experts Mitchell Katz, SVP, global clinical operations at Kyowa Kirin; Jessica Powell, VP, clinical operations at Alto Neuroscience; and Michael Krams, chief quantitative medicine officer at Exscientia, sat down with Comer to discuss current best practices for designing clinical trials that secure FDA approval and provide significant benefit to the patient. The wide-ranging discussion produced several key takeaways, including direct insights into how these seasoned drug developers have approached protocol design, collaboration with patient advocacy groups, and FDA relationship-building.
Determine What To Include (And What To Leave Out) Of Your Phase 2 Clinical Trial
Designing a protocol requires thoughtful consideration of what should be included and what can be left out. To help you navigate this process, the expert panel recommends building a strong relationship with regulators and collaborating with other sponsors to gain insight into what components are critical to include and what might be overkill.
According to Katz, “The beauty of drug development is the fact that it gives us an opportunity to share with colleagues across the industry and… look at the competitive landscape to see what other organizations are doing. If we have a good relationship with regulators, we have a good sense of what we want to do as far as our regulatory and clinical strategy. They guide you and make recommendations as to what [at a minimum] you should put into a protocol to help you ask the questions you want [to answer] as an organization.”
Leverage A Model-Informed Drug Discovery And Development Program
One innovative mechanism for intelligent trial design is using physiologically based pharmacokinetic (PBPK) models to anticipate how drugs will react in different physiological states. The results of these simulations can be used to identify and implement thoughtful methodologies that account for any potential obstacles. Krams, a proponent of PBPK modeling, outlined his recommended strategy as such, “I personally subscribe to the philosophy of model-informed drug discovery and development. I want to integrate all available information through modeling. I have been trying to engage my colleagues in early development and Phase 2 studies to routinely take appropriate PK sampling to enable modeling that would otherwise not be possible.”
Secure Buy-in For Biomarkers In Trial Protocol
Per the FDA, a biomarker is, “a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or biological responses to a therapeutic intervention.”1 When considering biomarkers in your trial protocol design, it is important to be cognizant of what the FDA deems acceptable to ensure you are using them effectively. Powell noted, “There are very few biomarkers that are truly validated and accepted by the regulatory agencies currently, so having their buy-in is critical… There are a lot of drugs in development right now that have a particular mechanism of action that may not translate into measurable clinical improvement for the patient. You have to understand the agency’s position for the particular division that you're working with; it is going to vary across the regulators.”
Understand FDA Expectations Early
To improve your chances of securing FDA approval, you need an early understanding of FDA expectations. Some sponsors opt to work with former FDA investigators who are now private consultants; this enables drug development teams to understand how FDA members are assessing drugs in different therapeutic areas. Powell also recommends taking advantage of the pre-IND meeting: “You get to understand what they are thinking about, [including] their concerns about not only your development pathway but your safety profile before you ever file anything. It is worth the time to put your package together to get this early feedback from the FDA before you start development.” Though it may seem obvious, it is critical to heed their advice and implement it into your activities; by demonstrating that you value their feedback and guidance, you place yourself in a strong position for approval.
Engage Patients & Investigators To Improve Trial Performance
Effective trials incorporate the patient perspective from the earliest stages of development. This can be done in a variety of ways, including engaging patients directly, working with patient advocacy groups to develop protocols, and gaining insight from clinical sites and their principal investigators. By creating trials that accommodate a diverse patient pool, you enable safety and efficacy across an array of populations. From Katz’s point of view, “Getting [patients] involved and working with advocacy groups has really enabled us to understand what the unmet medical need is from a patient perspective.”
Reference Best Practices For Trial Control Arms
When it comes time to make decisions about clinical trial control arms, consult with regulatory authorities who can advise on the specifics, including which comparator to use and the number of patients needed for a given study arm. Katz describes his experience of collaborating with regulators on trial control arms as such: “[Regulators] are anxious to get new meds to meet unmet medical needs, so they are very supportive. They give us recommendations on what control arm we should be using and what we should compare against. It has helped us tremendously on the development side.”
Creating a successful clinical trial takes a collaborative effort between sponsors, regulators, patient advocacy groups, and patient stakeholders. If you’re ready to gain more insight into the do’s and don’ts of clinical trials, click here to view the full webinar.
References:
- Amur, S. (2015, January 5). From our perspective: Clinical biomarker qualification. U.S. Food and Drug Administration. https://www.fda.gov/drugs/news-events-human-drugs/our-perspective-clinical-biomarker-qualification