FDA Dispute Resolution Process (CDRH)

Regulatory science is often considered a tricky subject since it mostly involves absolutes or issues that are not distinctively black or white. In such cases, regulators make decisions based on the basis of their best judgements formed in the context of the law, implementing regulations, and previous decisions on similar cases. In some cases, regulations are not sharply drawn and can lead to more than one conclusion. These can lead to strong differences in viewpoints between the FDA's decision and the officials of the medical device industry.

Such disputes with the FDA decision can be reviewed or reconsidered by the Dispute Resolution Processes. These processes are explained in Title 21 of the Code of Federal Regulations (CFR). These processes are applicable to resolve disputes involving 510k, PMA, IDE or PDP. The primary processes are often informal involving submission of a petition requesting change or internal review. The advantages and disadvantages of these processes are seen in the image below.

Other, more formal processes can be considered. These are often time-consuming and involve hearings either in a court, or before a board of scientists, an advisory committee, or the FDA Commissioner. The advantages and disadvantages of these processes are seen in the image below.

Other specific appeal processes are available for issues involving:
*Premarket Notification
*Investigational Device Exemption
*Product Development Protocol
*Premarket Approval
*Humanitarian Device Exemption
*Post-Market Surveillance Issues
*Regulatory Compliance Issues
*Product Designation Issues and other
*Miscellaneous Issues
These appeal processes can be seen explained in the "Medical Device Appeals and Complaints" document of the FDA. (http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM094523.pdf)

Clinical Trials

Clinical trials are defined by the FDA as, "trials to evaluate the effectiveness, safety and toxicity of medications or medical devices by monitoring their effects on large groups of people". Clinical trials have to be approved by the IRB and they are an essential part of PMAs. Good Clinical Practices (GCPs) are employed to maintain a regulated approach to clinical trials.

Clinical trials can be categorized into different types based on what they are done for.
1. Treatment trials - These seek to find new treatment approaches or compare to identify the most effective treatment available.
2. Prevention trials - They are done to identify approaches to prevent a specific type of disease from developing in people not exposed to it previously.
3. Early detection/screening trials - They are done to find new ways to identify a specific disease/problem in people even before they develop symptoms.
4. Diagnostic trials - These are done to figure out how new tests or procedures can be used to identify a specific disease in suspected population.
5. Quality of life/ supportive care trials - These trials try to identify ways of improving the comfort and quality of life for people with a disease/problem.

The results of a clinical trial is of much significance. Irrespective of the number of subjects or data involved in a clinical trial, the outcome is usually one of the following four types (in case of treatment trial):

Positive trial ‐ Superior (new treatment is better than standard treatment)
Non‐inferior trial ‐ Equivalence (new treatment is equivalent to standard treatment)
Inconclusive trial ‐ Neither superior nor inferior (new treatment is not clearly better nor clearly worse than the standard treatment)
Negative trial ‐ Inferior (new treatment is worse than the standard treatment)

A clinical trial usually starts with a clear investigational plan and an IRB approval for the study. Some components to be considered in the investigational plan are:
– Clinical study protocol - Study, hypothesis and design; Primary and secondary endpoints; Inclusion/exclusion criteria; Sample size and statistical analysis. It is essential to have a clearly defined and firm study protocol that cannot be changed during the course of the study.
– Risk analysis
– Informed consent form
– Case report forms
– Investigator agreement
– Clinical sites (number of sites / investigators / IRBs)
– Bibliography
– Instructions for Use
– Clinical study duration