Biomedical product development is an expensive, resource intensive process that requires extensive planning to ensure the product achieves market authorization within a defined timeline. Your clinical data may provide the most influential support for that market authorization, and therefore, your clinical study requires a development process that is as carefully planned and robust as your overarching product development process.
While clinical studies are usually initiated after most other design verification and validation (DV&V) tests have been completed, they are the ultimate validation test and should never be handled as an afterthought. Rather, the planning for clinical studies needs to start early in DV&V planning stages.
At Bright, we follow a 6-step clinical study development process. Let’s dive in to review this process, and along the way we’ll share several well-honed tips that will increase the likelihood for smooth and successful execution of your clinical study.
Define Your Strategy
If a clinical study is required by your DV&V plan (to support the eventual market authorization application), clinical study planning should occur in conjunction with the following activities: risk analysis, creation of DV&V test plans, and drafting of proposed labeling, especially the indications, contraindications, and potential adverse events.
Here are a few tips to keep in mind during the strategy phase:
- Led by a clinical literature review that assesses comparable devices, your risk management program will help identify possible clinical study endpoints and potential adverse events you may expect to encounter during your own clinical study.
- Engage with marketing, clinical, and regulatory team members to help define the user inputs (or clinical needs), and make sure to obtain input from key opinion leaders and medical advisors in your clinical space. These user inputs will help you define and refine clinical endpoint measures, assessments, and labeling claims.
- By planning verification and validation together, you may find smart ways to meet user requirements. For example, some human factors requirements can be evaluated in the clinical study, thereby eliminating the need for a separate usability study. Similarly, some clinical endpoints may best be evaluated in a well-established animal model.
Refine Your Study Design
Heard of “fail fast, fail cheap”? At Bright, we say “engage FDA early and often (and for free).” The FDA pre-submission process is a free, informal, and non-binding way to build a relationship with FDA while you introduce your device and obtain feedback on your development approach.
During the pre-submission process, FDA can confirm that your proposed suite of bench, biocompatibility, sterilization, and pre-clinical animal tests appropriately challenges your product, supports your proposed indications, and meets their expectations with respect to current standards and market authorization requirements. A solid battery of non-clinical tests paves the way toward product use in humans.
The pre-submission process is free and relatively fast, but if your product is novel or particularly complex, ensure your plan allows for multiple rounds with FDA to negotiate and iterate on those test plans before you execute them. Think of it as “going slow to go fast.” You’re doing this testing anyway, so do it right and avoid a costly scenario of repeat tests that delay your clinical study for months. Fact: Repeating chronic GLP animal studies is not in your plan, your timeline, your budget, or anyone’s interest.
While you wait for FDA’s feedback, engage with potential investigators and sites to survey and characterize their interest and capability to participate in the study. This is a low-cost and potentially high-reward activity that accelerates site qualification, start-up, and activation when the time is right.
Freeze Your Study Design
With FDA feedback in hand, update affected DV&V plans and begin the non-clinical tests with confidence. Meanwhile, prepare the clinical deliverables that will be needed for your investigational device exemption (IDE) submission, including final drafts of the study protocol, informed consent, and case report forms. Plan to submit final drafts in the IDE, as FDA may have final requirements or recommendations you’ll need to incorporate. You can also start the IDE application with placeholders for the pending non-clinical verification results.
As the verification data comes in, there may be failures or other unexpected details to address. Be sure that any updates made to risk analyses, product design, or test plans are assessed for impact on the clinical development process and associated documentation. For example, if product dimensions or materials change, you may need to update the clinical protocol device description. If new potential adverse events are identified, incorporate that information into the protocol, informed consent, and product labeling.
Many sites can negotiate clinical study agreements or prepare Institutional Review Board (IRB) submissions in advance of IDE approval. Take advantage of this wherever possible, as contract and budget negotiations and IRB approvals are often the longest lead time items for site activation.
(Semi) Conclusion
This is a good spot to freeze the blog too. Please stay tuned for part 2 in which we’ll discuss study launch, maintenance, and closure. In the meantime, happy defining, refining, and freezing, and always planning!
