US patients wait on average a full two years longer than their European counterparts for many lifesaving and life-enhancing technologies made by US medical device and diagnostics companies because of growing regulatory delays and inefficiencies, according to a new study. And while there is some controversy as to whether the study represents a true picture of the problem, it highlights some recurring themes and attempts to quantify what has been up to now only anecdotal reports.

"The data show that the US is at risk of losing its global leadership position in medical technology innovation,” said Josh Makower, MD, a consulting professor of medicine at Stanford University and a medical device entrepreneur. Makower, who is one of the co-authors of the study, said that the unpredictability and inefficiencies in the US regulatory process are making it difficult for companies to get life-changing medical products into the hands of clinicians and patients.

“The global financial crisis has created a tremendous pressure on small companies in the United States. Venture Capital funding is very difficult to get right now. And the challenges that have been reported on the regulatory process are making this worse and really pose serious threats to medical innovation and therefore threats to advancing patient care,” said Makower.

Makower and coauthor Aabed Meer, with the support of the Medical Device Manufacturers Association and the National Venture Capital Association, surveyed more than 200 small- and medium-sized medical technology companies to evaluate the impact of the current FDA regulatory processes on innovation. The study used Europe as a benchmark. The study found that for low- and moderate-risk devices, the process to navigate the FDA took companies between three months to two years longer for clearance or approval than it did for a similar approval from European regulators. For higher-risk devices, the discrepancy was greater—the process in the United States took three- and- a- half years (five times as long as Europe) to grant approval.

By overwhelming majorities, the companies surveyed reported that European regulatory authorities were more predictable and more transparent than FDA. Almost half the companies reported that key FDA personnel responsible for reviewing their product changed during the course of the review, and one-third reported that appropriate staff were not present at meetings between the companies and FDA to discuss review issues.

Speaking at the annual FDA update at the Mass. Medical Society sponsored by Massachusetts Medical Device Industry Council, CDRH director Jeffrey Shuren, MD, discounted the results of the findings, calling the sample too small and the assessment of the agency unfair.

But Makower points to a recurring theme from the surveyed companies: changing reviewers leads to changing requirements and more delays. “As you look at where the issues are coming from,” said Makower, they stem from several inefficiencies to the process and tremendous turnover at FDA. This creates a lot of uncertainty.” He said that companies that have an agreed-upon protocol, execute the clinical trial, and then return to find that the reviewing group at FDA is no longer the same. “That group may no longer agree with the group that was there when the study was agreed to,” he said. “They find themselves in the very difficult position of being asked to do another study, even thought they thought they were doing the one FDA wanted.” He said that this scenario happens about 44% of the time.

Of particular concern for small companies is the financial impact, said Makower. “Small companies are such a great candidate for study because their survival on a month-to-month basis is really provided by the capital that they’re able to raise,” he said. “The amount that it costs to keep everyone employed and all the right engineers, scientists, and so on in place, over that period of time is a fixed variable that cannot change. But if the time changes for navigating the process, then the expense greatly increases. They have to raise more money.”

The survey data showed that the average total cost for participants to bring a low- to moderate-risk 510(k) product from concept to clearance was approximately $31 million, with $24 million spent on FDA-dependent or related activities. For a higher-risk PMA product, the average total cost from concept to approval was approximately $94 million, with $75 million spent on stages linked to the FDA.

"The current regulatory environment is putting our nation's fragile medical innovation infrastructure at risk," Makower said. "FDA and innovators share the common goal of improving patient care. To achieve this objective, FDA and industry must work together towards a reasonable and balanced regulatory process for new innovations. This will ensure that patients and clinicians have timely access to safe and effective products. Only then will the most cost effective advances in medical care be delivered; and only then will the public health and our economy be best served."

Whether the study is a truly representative sampling of industry is still up for debate. But for this group, the problems are real and deserve the agency’s attention.