The FDA is charged with ensuring that the new medical devices it allows onto the market in the United States are safe and effective, and can reach the public in a timely way. By statute, safety and effectiveness must be based on valid scientific evidence. However, the FDA is not necessarily responsible for ensuring that the process is cost-effective when companies are working to prove that their devices will produce clinically significant results when used for their intended purposes. It is a necessarily tough process that can be expensive and time consuming, but there are some considerations that can be taken into account to mitigate the difficulty of getting a new device to market.
An examination of the orthopedic and spine PMAs shows that approvals can typically take an average of 26 months, but range anywhere from 9 to 42 months. (However, there are outliers. In 2009, one hip device was cleared after 74 months of review.) To further break it down, spine approvals averaged 18.3 months in review, while the orthopedic approvals averaged 29.6 months in review. Additionally, the review times have been trending higher in recent years, while the number of cleared PMAs has grown smaller at the same time.
The reason for this is that the standards for clinical evidence have been growing more stringent over the past 10 years. Up to 2006, the approval process simply focused on the following questions:
- Did you “win” the study by demonstrating non-inferiority?
- Was the proper indication studied, and was the control group correctly matched to the treatment group?
- Was patient accountability high?
- Was a simple, but proper, statistical plan utilized?
- Were adverse events understood, and is a plan to mitigate them properly implemented?
- Were there quality study sites?
- Are good manufacturing processes in place?
When comparing spine and general orthopedic PMA approval timelines, it is clear that the answers to these questions play a large role in affecting outcomes. A side-by-side comparison of some areas where these PMAs differ is revealing:
Newer PMA applications also are seeing a greater rigor, which has already been reflected in many of the spine PMAs approved by the FDA, thus explaining why spine PMAs have a smaller average review time. The agency now demands a greater emphasis on:
- Data analysis independence- elimination of bias
- Study safety measures- implementation of stopping rules
- Radiographic protocol- determine what is happening at the biomechanical level
- Good manufacturing processes- scrutiny of cleaning and sterilization processes
- New concerns- materials, radiographic “safety”, and mechanism of action
There are also more detailed risk-benefit determinations. Reviewers now expect peri-operative measurements, amongst other metrics, as part of the data package accompanying PMA applications. This is simply because the FDA is seeking the highest scientific rigor, in order to maximize patient safety.
How can companies optimize their navigation of the PMA process? The recipe is simple:
- Have adequate pre-clinical testing
- Demonstrate non-inferiority
- Maintain high patient accountability
- Ensure development of a positive risk/benefit profile
- Minimize “unexpected” adverse events and observations
- Clearly demonstrate the device’s mechanism of action
- Eliminate potential sources of bias during data gathering and analysis
- Maintain a validated manufacturing process
While the PMA process will be getting more and more difficult in the coming years, there are certainly ways to effectively and affordably bring medical devices through the PMA process. It takes careful planning, and knowledge of what the FDA is looking for.