Medical Device Blog – QA & Regulatory Updates from Emergo Group

Guidance published by the FDA in late 2011 intends to update regulatory requirements for medical device manufacturers responding to public and non-public requests for off-label information about their products.

Now that online forums, email, social networking sites and other more advanced communication methods have become more widely used, the FDA has revised its approach to off-label information requests to take into account these new electronic communication methods.

The guidance reiterates the agency’s longstanding policy that a manufacturer’s responding to unsolicited requests for off-label information in such a way that suggests an unapproved intended use for the device in question is prohibited.

Public requests for off-label information
The FDA distinguishes between public unsolicited requests for off-label information—those made in public forums and directed either to an individual firm or to a wider forum—and non-public requests, which are directed privately to individual firms using one-on-one communication methods.

The guidance includes electronic communications under the public request category; consumers more often conduct online research on medical products and technologies, and off-label use questions from consumers are often seen by other online consumers as well as firms. Concerned that manufacturers may respond to individual requests for off-label data via online, public methods—particularly if those responses include intended use information that does not square with FDA approval—the agency recommends responding privately to any public request for such information. In the event that a firm opts to respond publicly, however, the FDA guidance provides the following suggestions:

• A firm should only reply to online public unsolicited off-label information requests in terms of specific information regarding its own products—not competitors’ products
• A firm’s public  response to an information request should only consist of the firm’s contact details, not any off-label data
• Any representatives of manufacturers responding publicly to questions regarding off-label information should fully disclose their relationship to those manufacturers
• Public responses to such requests should not promote or market the device or manufacturer in question

Compliance issues
Medical device industry participants have until March to submit comments on the FDA guidance. Assuming the guidance is implemented, what will manufacturers need to do in order to comply? An analysis by MDDI suggests firms revise standard operating procedures and policies regarding electronic communications, as well as potentially rope in regulatory affairs departments for any online and social media campaigns that could result in unsolicited off-label information requests—and FDA scrutiny. 

The Obama Administration has announced plans to require medical device and pharmaceutical companies to report payments they make to US doctor and other health care providers for research, consulting and travel.

According to a recent New York Times report (tiered subscription required), the new rules are designed to tackle influence these payments have on doctors’ treatment decisions; payment from a medical device manufacturer to a doctor has the potential to make it likelier that that doctor will prescribe that manufacturer’s device instead of cheaper alternatives, evidence suggests.

The new rules will require companies with at least one product covered by Medicare or Medicaid to disclose all payments to doctors who are not their own employees. Payment data they provide will be published online.

Types of payments falling under these requirements include compensation for development, assessment or promotion of new products as well as royalty payments to inventors, payments to teaching hospitals for research and even “$25 worth of bagels and coffee to a doctor’s office for a meeting.” Companies’ chief executives, chief financial officers and/or chief compliance officers must attest to each report’s accuracy.

Administration officials believe more than 1,100 firms will be impacted by the new rules; failure to comply will incur penalties of up to $10,000 for each payment a firm fails to disclose. Knowingly failing to report payments will incur penalties of up to $100,000 per violation, capped at $1 million per year.

The Centers for Medicare & Medicaid Services (CMS) is accepting public comment on the rules through February 17^th, after which final rules will be implemented. 

New draft guidance from the US Food and Drug Administration recommends improvements to medical device manufacturers’ clinical study designs in order to better assess safety and effectiveness of their products according to gender.

The guidance aims to suggest methods to enroll more women in clinical studies in order to better represent demographic distributions of particular diseases; identify statistical analyses of study data that take into account gender differences; emphasize the need to consider gender differences during manufacturers’ study design phases; and spell out expectations of the Center for Devices and Radiological Health (CDRH) for reporting of sex- and gender-related information in study summaries and labeling for approved or cleared devices.

“Certain medical products elicit different responses in women compared to men,” the guidance states, citing ventricular assist devices and cardiac resynchronization therapy defibrillators as examples of devices with significant differences in effectiveness between male and female patients.

“Many clinical studies do not enroll proportions of women that reflect the underlying disease distribution in the affected population… This has contributed to a substantial lack of available data regarding the risks and benefits of medical device use in women.”

Historical barriers to enrollment of women in clinical studies, according to the FDA, include fears of fetal consequences, avoidance of female subjects by study sponsors, and study inclusion or exclusion criteria that inadvertently exclude women. To reduce these challenges, study sponsors and manufacturers should examine screening logs in order to track reasons for non-enrollment of women as subjects.

What to include in submission documents
The guidance recommends inclusion of information such as sex-specific prevalence of the disease in question, sex-specific diagnosis and treatment patterns, identification of proportions for women included in past clinical studies, and identification of any known clinically significant sex differences in outcomes regarding safety or effectiveness.

For new and ongoing studies, manufacturers and sponsors should include the afore-mentioned data as components of the risk analysis sections of their investigational plans. Firms should also summarize this information in their study protocols and training materials.

For completed studies, this data should be included as part of your marketing application under clinical investigation results. A draft PMA Summaries of Safety and Effectiveness or 510(k) Summary should also include this information.

Finally, for postmarket studies, this information should be included in interim reports as well as the results sections of final reports.

Other Recommendations
In addition, the FDA guidance recommends clinical study investigators take into account how the influence of subjects’ sex affects primary endpoints for safety and effectiveness. Analysis of subgroups and testing for interaction or heterogeneity may also be necessary, according to the agency.

Statistical analysis must also address sex-specific issues, recommends the FDA. Any clinically significant sex differences should be reported and discussed with FDA personnel to see whether further investigations are required based on those findings. Sex-specific information should also be reflected more thoroughly in study summaries and labeling, according to the guidance.

US medical device manufacturers dealing with lower market demand and rising pricing pressure will rely more on acquisitions and stock maneuverings to offset challenging growth prospects.

Moody’s Investor Service (via MarketWatch) anticipates slow sales for medical device firms over the next 12 to 18 months—especially for devices such as orthopedics used in elective procedures and cardiac products drawing more regulatory scrutiny due to safety and effectiveness concerns.

A weak global economy will necessitate share buy-backs, acquisitions and dividends by many firms in order to minimize losses, according to Moody’s. The ratings agency expects manufacturers to primarily borrow capital in order to fund such activities, which could negatively impact their credit standing.