Getting a medical device to market is not easy. The Food and Drug Administration (FDA) approval process alone can take years and millions of dollars. In 2011, the FDA and the Centers for Medicare and Medicaid Services (CMS) noted another lengthy procedure: “It has come to our attention that innovators have generally focused solely on obtaining FDA approval, only to later realize that Medicare payment may not automatically be forthcoming.” Indeed CMS’s national coverage determination (NCD) for a product or service can add significant time and cost.
FDA and CMS solicited comments from industry on the concept of a “parallel review process” in 2010. In 2011, they officially launched the Pilot Program for Parallel Review of Medical Products. “The parallel review program has the potential to increase patient access to innovative devices that improve clinical outcomes," noted Patrick Conway, M.D., CMS chief medical officer. "Our goal is to reduce regulatory burden and improve patient outcomes,”
FDA stated that “[b]y reducing the interval between FDA marketing approval and Medical coverage, this process will facilitate the development of innovative products and shorten the time it takes to bring these important products to patients.”
The agencies note that during the parallel review "pilot phase," they will offer to perform parallel review for up to five innovative devices per year. Appropriate candidates for the pilot are medical devices that meet one of the following criteria:
- New technologies that would require an original or supplemental application for premarket approval (PMA) or a petition for de novo review.
- New technologies for which the sponsor/requester has a pre-investigational device exemption (IDE) or an approved IDE application designation.
- New technologies that fall within the scope of a Part A or Part B Medicare benefit category and are not subject to a national coverage decision (NCD).
Initial critique of the parallel process focused on the fact that the agencies have always worked independently. During the comment period in 2010, industry noted a number of concerns, including that companies could be at risk for a possible breach of confidentiality and company trade secrets due to Medicare’s practice of making information publically available for comment. Others noted that problems may arise due to the distinct roles of FDA’s requirement that products be “safe and effective” and CMS’s concern that they be “medically necessary.”
Despite the comments, the first device has successfully made its way through the parallel review. The FDA's announcement details the device named "Cologuard":
The U.S. Food and Drug Administration today approved Cologuard, the first stool-based colorectal screening test that detects the presence of red blood cells and DNA mutations that may indicate the presence of certain kinds of abnormal growths that may be cancers such as colon cancer or precursors to cancer.
Using a stool sample, Cologuard detects hemoglobin, a protein molecule that is a component of blood. Cologuard also detects certain mutations associated with colorectal cancer in the DNA of cells shed by advanced adenomas as stool moves through the large intestine and rectum. Patients with positive test results are advised to undergo a diagnostic colonoscopy.
In a clinical trial, Cologuard detected 92% of colorectal cancers and 42% of advanced adenomas, which are large polyps that are more likely than small polyps to lead to cancer. A traditional stool test was less accurate, detecting 74% of cancers and 24% of advanced adenomas.
Last week, MedDevice Online detailed the parallel review process, and spoke to many of the key stakeholders involved:
[T]he linchpin of parallel review is increased interaction between the primary stakeholders, ideally leading to a clinical trial design that meets the needs of all parties involved. “These conversations are very different and in the past have been very disconnected,” said Michael Tarnoff, M.D., Covidien’s corporate chief medical officer and moderator of the AdvaMed panel. “You can end up spending millions of dollars on a clinical trial only to have Medicare say that your endpoints are relevant to the regulator, but they are not as relevant to the payer.”
The parallel review model endeavors to avoid this scenario by bringing everyone together during the very early stages — starting with (or even before) an investigational device exemption (IDE) submission. For example, CMS may attend a pre-IDE meeting in what CMS’s Syrek Jensen called “listening mode” to get a better idea of what the proposed trial will look like. Then, it will provide its input and have conversations with the device maker and FDA later, often via email or over the phone. Suggestions might include enrolling older patients in the study or taking into account endpoints that you normally wouldn’t in a safety/efficacy-focused trial, like quality-of-life and economic measures.
Kevin Conroy of Exact Sciences, the company behind the Cologuard, spoke to how the collaborative approach brought about a much better result than going through two processes independently. “It was pretty straightforward--FDA gave its inputs on the clinical trial design, and CMS gave its inputs. They were really logical, and we incorporated them fairly quickly,” he said. “We ended up enriching the patient population for Medicare, which actually had the unintended consequence of shortening the trial.”
The article concluded:
That’s the appeal of the parallel review concept. Everyone benefits from a more efficient process. Manufacturers avoid additional clinical trials and realize quicker returns on their product development investments. CDRH achieves its vision statement by providing U.S. patients with high-quality, safe, and effective medical devices — “first in the world.” And CMS delivers new technologies that have a meaningful impact on health outcomes to its population.
While the pilot program was originally intended to run through the end of 2013, FDA and CMS announced last December that it would continue through December 18, 2015. In addition to the Cologuard from Exact Sciences, the only other known parallel review participant is Medtronic’s Symplicity renal denervation system. In January of this year, however, Medtronic announced that the device's Phase III trial had not met its primary efficacy endpoint (Regulatory Affairs). This setback potentially could have derailed the FDA-CMS pilot program going forward.
Cologuard is thus a welcome success for both industry and the government. We will continue to follow updates to this collaborative process.