StageBio clients often ask for expert guidance when it comes to developing a protocol for the pathology work of their medical device studies. Senior Pathologist Lynette Phillips, DVM, PhD, DACVP, held a live webinar event to demystify several preclinical pathology operations which are crucial to a study’s success.

The webinar, titled “Key Pathology Considerations for Successful Preclinical Medical Device Studies, from Protocol to Report,” is now available for on-demand viewing.

The key considerations Dr. Phillips shares during the 60-minute webinar are designed to help you add clarity and specificity to protocol instructions. Among the topics covered are:

• The protocol role in study pathology success
• A systematic approach to understanding and planning pathology work
• Common pathology evaluation strategies

Watch the full webinar for an in-depth explanation of each consideration. You can also continue reading for a quick summary of select sections.

The protocol: A blueprint for pathology success

During the webinar, Dr. Phillips describes the protocol as the study’s blueprint for study success. As such, the protocol spans both pathology-adjacent and pathology-specific sections.

Pathology-adjacent sections define the study context and its determinants:

• Study objectives
• Study endpoints
• Success (acceptance) criteria
• Regulatory compliance
• The test system
• Study design
• Test articles and controls
• Reporting

Pathology-specific sections define the technical pathology work:

• Necropsy examination, sample handling
• Histology work (slide preparation)
• Histopathology evaluation
• Ancillary pathology tasks (e.g., histomorphometry, specialized imaging)

How do you know when pathology is required?

When medical device study objectives include keywords like safety, efficacy, tissue response, or performance, a pathology evaluation is commonly required. A study will require pathology work if endpoints include tasks such as necropsy, histopathology, or histomorphometry, for example.

Developing effective success criteria for pathology

As Dr. Dr. Phillips explains, highly limiting conditions for success criteria increase the chances that your study may face unrealistic standards. She recommends the use of unambiguous, defined criteria tailored to study conditions. Examples of phrases commonly used include:

• Comparable to
• Better than
• Not observed

Conversely, rigid standards such as “equivalent to” should be avoided.

To evaluate pathology results in the appropriate context, Dr. Phillips encourages use of the phrase, “As expected in this model,” for success criteria, especially for studies where model limitations may negatively influence results.

Study-defining activities

Dr. Phillips states that certain study conditions influencing the pathology evaluation are predetermined; these include the animal model (test system) and the study design (test/control articles or treatments, cohort designations, numbers, and timepoints).

Control selection

Dr. Phillips recommends selecting a control with a healing profile comparable to your test article whenever possible. For biodegradable devices, it's preferable that the control article has a similar resorptive mechanism.

If quantitative assessment of residual biodegradable material is a required evaluation for the test/control articles, then a baseline implant sample may be necessary.

When selecting a control for your study, you should assess any confounding risks by asking yourself these questions:

• Is it a true control?
• By use of this control, can the test effects be isolated?

The ability of a study design to isolate test effects is a focus for regulatory agencies, making the latter question especially important.

Dr. Phillips recommends avoiding historical controls in preclinical studies. Regulatory agencies, including the FDA, prefer the control used in a medical device study to be contemporary with the environment in which the testing is being conducted.

However, what if a study doesn’t have a control? Absence of a control article is common with early investigative studies or those testing innovative technology. When no control is present, Dr. Phillips stresses the importance of developing appropriate non-comparative (absolute) scoring and success criteria appropriate for your test article.

Watch the on-demand webinar and learn the other key pathology considerations for successful preclinical medical device studies

In the webinar, Dr. Phillips continues to unpack key considerations regarding pathology-directed activities, including:

• Creating specific, directed tasks as a best practice
• Providing valid data and drawing contextual study conclusions
• Avoiding nonspecific pathology instructions in the protocol

She also explains common pathology nomenclature, activities, and pathology tasks for both implant and non-implant medical device studies.

Access the on-demand webinar here, and learn sampling and histology considerations, best practices for macroscopic examinations, tips for selecting slide stains, histopathology evaluation types, and more.