“Wait a minute, what did you just say?” More than once we’ve paused a conversation with clients to ask that question because hints about potential study-impacting changes were hidden within routine conversations or off-handed remarks.
The trickle-down effects of change are often underestimated, and the impacts on clinical study timelines and budgets can range anywhere from modest to significant. Let’s review a few scenarios involving changes to product design, site-related logistics, and sponsor business locations, and we’ll wrap up with a few tips for ensuring a systematic process for study change impact assessment (CIA).
Product Design
All medical device manufacturers who comply with FDA design control regulations have written CIA processes to ensure a systemic method for evaluating product and process changes. A variety of functional groups are usually involved in the assessment, and if the product requires clinical validation, the clinical team should definitely be in the loop.
The CIA process should assess impact on the clinical study, whether the study is in the planning stage or already in progress. Here are a few examples to illustrate potential impacts of proposed design changes on the clinical study:
- If a product design change requires FDA pre-approval before use in an ongoing study, the regulatory review process could add several months to the project timeline. Several documents will need to be updated, reviewed, and approved, including the study protocol and investigator’s brochure.
- If a literature review identifies new risks, this may drive updates to the risk assessment, product labeling (e.g., IFU), study protocol, and the informed consent form. It might take several weeks or even longer to review and approve the document changes, and more importantly, the FDA and IRBs will likely need to approve several of these documents.
- If product labeling needs to be updated to include new contraindications or warnings, this may delay the availability of investigational product inventory, which may impact subject enrollment rates. In addition, updates would likely be needed to several sections within the study protocol (e.g., exclusion criteria, list of potential adverse events, and treatment procedures) and the informed consent form, both of which may require FDA and IRB approval.
- If a new product design will be implemented during the study, this may have an impact on sample sizes, which could have significant impacts on the study budget and timeline. The study protocol and statistical analysis plan would need to be updated, and you know the drill by now about regulatory approvals for these documents.
- Note: Clinical studies must be performed using investigational devices that are representative of the commercial product. If the product design changes mid-study, be prepared to provide rationale on why the clinical data collected on the previous design is considered representative of the design that will be commercialized.
Site-Related Logistics
During the study design stage, careful thought goes into numerous logistical and procedural details to support smooth, efficient enrollment and robust compliance with the study protocol. Even seemingly small changes should go through a thoughtful impact assessment to prevent unintended hiccups with site logistics. Below are a few examples of site-related impacts.
- If a principal investigator (PI), sub-investigator, or research coordinator leaves a site mid-study, either temporarily (e.g., parental leave) or permanently, several impacts will need to be assessed and addressed. At minimum, you’ll need to train replacement personnel, update site contact lists, and update access privileges within the electronic data capture (EDC) system. For PIs and sub-investigators, you’ll also need to execute agreements, obtain financial disclosures, and get copies of their CVs.
- If a sponsor decides mid-study to add an eConsent platform, that might seem like a simple streamline; however, make sure the data management team weighs in on behind-the-scenes logistics. The FDA and IRBs need to pre-approve any patient-facing materials, and this topic is complex enough that FDA has issued a document entitled “Use of Electronic Consent: Questions and Answers.” As suggested within that document, before you invest time in developing an eConsent platform, talk with IRBs about your plans to ensure they agree this format may be used for your study.
Sponsor Business Locations
When a business changes location (especially for the investigational product manufacturing facility), study-related documentation can be easily overlooked amidst the myriad logistical details that need to be managed. Remember, though, that the sponsor address is listed on several study-related documents, including the study protocol, investigator’s brochure, IFU, and product labels. Changes to these documents may require FDA and IRB submission or notification.
While most of our examples are focused on assessing the impact of changes, here’s an insider tip: It’s a wise approach to anticipate potential change management burdens when you design your clinical document templates. Do not include superfluous information, which means only include the sponsor address on documents where it is necessary. If the address changes, your document change paperwork load will be less burdensome.
Study CIA Checklist
To ensure a thorough, systematic process for evaluating study-impacting changes, we recommend that you create a thoughtfully designed study CIA checklist. Our Bright checklist has more than 40 line items that identify key study-related documents, plus sections to assess regulatory and statistical impacts. The checklist includes documents related to study design, investigator and site qualification, safety committees, core labs, start-up logistics, launch preparation, enrollment, on-going study management, and close-out.
Whew! It would take a photographic memory to remember all the inter-connected documents and logistics summarized on the study CIA checklist. You’ll be glad to have this tool ready the next time you hear hints of study-impacting change. Wait a minute, what did you just say? Oh, you’re welcome; we’re happy to help.
