FDA Issues Two Final Guidances on Communications Not Included In Product Labeling
Last month, FDA issued two final guidances on medical product communications, including communications by medical device companies about unapproved uses of approved/cleared medical products: “Medical Product Communications That Are With the FDA-Required Laveling—Questions and Answers” (CWL Guidance) and “Drug and Device Manufacturer Communications With Payors, Formulary Committees, and Similar Entities—Questions and Answers” (Payor Guidance). Taken together, these guidances provide considerable additional flexibility for medical device manufacturers to communicate truthful and non-misleading information about their products to health care professionals, payers, and other customers.
Although the final guidances are largely consistent with the draft guidances, issued in early 2017 (available here and here), they provide answers to some questions left open by the draft guidances and new insights into FDA’s thinking on these issues.
The CWL Guidance outlines three factors that must be satisfied to be considered consistent with FDA-required labeling:
- The conditions for use expressed in the communication must be consistent with labeling with respect to the (a) indication, (b) patient population, (c) limitations and directions for handling/use, and (d) dosing or use regimen/administration;
- The representations/suggestions in the communication should not increase the potential for harm to health relative to information provided in the labeling; and
- The directions for use in the labeling should enable the product to be safely and effectively used under the conditions represented/suggested in the communication.
Information not included in the FDA-required labeling, but that could nonetheless be consistent with the labeling might include, among other things:
- Information about safety and efficacy from a head-to-head study with another medical product for the approved indication;
- Additional context about adverse reactions associated with approved uses;
- Information about long-term safety and/or efficacy of products approved for chronic use;
- Information about effects in specific patient subgroups included in the approved patient population;
- Information about effects in the approved patient population, for example if a prosthetic hip, approved to treat mobility-limiting joint disease, also decreases hip pain; and
- Information about convenience, for example if the product requires less time to administer as compared to another product approved for the same indication.
FDA instructs that “simply analyzing whether there is a conflict between the information in the communication and the FDA-required labeling is not always sufficient to determine whether a communication is consistent with the FDA-required labeling.” For example, a communication about Medical Product B that suggests a patient can be switched immediately from Medical Product A to Medical Product B may not be in direct conflict with the labeling for Medical Product B, and yet the communication would still be “inconsistent” with FDA-required labeling if some characteristic of Medical Product A makes switching from Medical Product A dangerous.
In addition, FDA indicates that it will not generally regard communications consistent with the labeling as establishing a new intended use. However, these communications may be considered evidence of a new intended use if “there is other evidence of a new intended use for a product.” In 2017, FDA announced that it would delay implementation of a final rule that would have altered the agency’s definition of “intended use” for drugs and devices. Critics of the final rule had argued that it included significant changes from the proposed rule, including that the agency would consider the “totality of the evidence” when assessing intended use. The implications of the statements in the final guidance regarding evidence of intended use will depend in part on how FDA ultimately resolves the suspended rulemaking, and whether FDA retains a “totality of the evidence” approach to determining intended use.
Further, the CWL Guidance makes clear that communications need not be based on evidence satisfying the “substantial evidence” standard necessary for approval/clearance of medical products. Instead, communications consistent with labeling must be supported by evidence that is “scientifically appropriate and statistically sound.” This lower standard requires disclosure of the “limitations of the strength of the evidence and the conclusions that can be drawn from it.” For example, FDA states that where data are not adequately powered or controlled for false positives, the firm could not include a claim or p-value (viewed as an indirect claim) but could present the data with context and material limitations. Such context could include an explanation “that because these analyses were not prespecified and appropriate multiplicity adjustments were not applied, the results on the individual components need cautious interpretation and could represent chance findings.”
FDA’s Payor Guidance addresses how manufacturers can communicate information to payors. The Food, Drug, and Cosmetic Act (FDCA) provides that manufacturers may communicate “health care economic information” to a “payor, formulary committee, or other similar entity with knowledge and expertise in the area of health care economic analysis” so long as the information “relates to” an approved indication and “is based on competent and reliable scientific evidence, and includes, where applicable, a conspicuous and prominent statement describing any material differences between the health care economic information” and the approved labeling. The statutory language applies on its face to drugs, not devices, but the final guidance makes clear that the recommendations set forth in the guidance apply to communications of health care economic information to payors regarding devices as well.
A noteworthy omission in the draft guidance was any discussion of whether or under what circumstances manufacturers may communicate health care economic information about unapproved uses of approved products. The final guidance expressly acknowledges that communicating such information may serve the agency’s public health goals because “payors, in some situations, need to plan for and make coverage and reimbursement decisions for medical products and uses far in advance of the effective date of such decisions.” The final guidance also makes clear that the statutory provision for “other similar entit[ies]” to which health care economic information may be communicated, is quite broad, and includes pharmacy benefit managers, third party administrators, technology assessment committees, and “other multidisciplinary entities.”
When communicating health care economic information to payors (and related entities) about unapproved products or about unapproved uses of approved/cleared/licensed products, FDA recommends that manufacturers include certain information intended to make clear that the products have not been determined to be safe and effective for the use discussed (or, for unapproved products, for any use).
The type of information about unapproved uses that FDA contemplates manufacturers sharing with payors includes information about the product and indication sought, anticipated timeline for approval/clearance, pricing information, patient utilization projections, patient services and programs, and clinical and preclinical data.