FDA Transparency Initiative: Draft Disclosure Policies

In addition to the recently published Nation Institutes of Health (NIH) transparency Guidelines, the Food and Drug Administration (FDA) this month released a report regarding the “FDA Transparency Initiative: Draft Proposals for Public Comment Regarding Disclosure Policies of the U.S. FDA.”

 

The Transparency Initiative, which was launched in June 2009 by FDA Commissioner Dr. Margaret Hamburg, was overseen by a Task Force representing key leaders of FDA, and was chaired by Joshua M. Sharfstein, M.D., Principal Deputy Commissioner of the FDA.  Since last June, the Task Force has held two public meetings.

 

At the first public meeting, an eight hour session was held, in which the Task Force solicited comments from thirty five individuals during the meeting on how the Agency could improve transparency overall. The second meeting solicited comments on three specific issues related to transparency at the Agency:

 

(1)  Early communication about emerging safety issues concerning FDA-regulated products;

(2)   Disclosure of information about product applications that are abandoned (no work is being done or will be undertaken to have the application approved) or withdrawn by the applicant before approval; and

(3)  Communication of Agency decisions about pending product applications. The Task Force also launched an online blog that has more than 1,500 comments, and opened a docket.

 

The Task Force carried out the Transparency Initiative in three phases.

 

Phase I: FDA Basics

 

The first phase was intended to provide the public with basic information about FDA and how the Agency does its work. This phase was unveiled in early January 2010 with the launch of a web-based resource called FDA Basics (www.fda.gov/fdabasics), which includes:

(1)  126 questions and answers about FDA and the products that the Agency regulates,

(2)  Nine short videos that explain various FDA activities, and

(3)  Ten conversations with FDA officials about the work of their Offices. Each month, senior officials from FDA product centers and offices host online sessions about a specific topic and answer questions from the public about that topic.

 

Phase II: Public Disclosure

 

The second phase relates to FDA’s policy on disclosure, in which the Task Force report offered 21 draft proposals for public comment regarding changes in the policy.

 

Phase III: Transparency to Regulated Industry

 

The third phase of the Transparency Initiative addresses ways FDA can become more transparent to regulated industry, in order to foster a more efficient and cost-effective regulatory process. The Task Force solicited comments from the public on this topic and draft proposals from this phase are expected in the summer of 2010.

 

Proposals for Comment

 

1)  FDA should expand the areas in which it provides the public with online access to public information from adverse event reports about FDA-regulated products submitted to FDA, in a format that is searchable and allows users to generate summary reports of this information, including, if known and as applicable, the trade name and/or established name of the product, dosage, route of administration, description of the adverse event, and the health outcome.

 

2)  In the weekly FDA publication, FDA Enforcement Report, FDA should disclose when the U.S. Department of Justice files a case seeking enforcement action on FDA’s behalf in a court of law and the final determination of that case, if known.

 

3)  FDA should post on its Web site all Agency Workplans (i.e., the annual Office of Regulatory Affairs Annual Field Workplan) that are older than five years, starting with the FY 2001 Workplan.

 

4)  FDA should disclose the outcome of the filer evaluation for importers or third parties working on behalf of importers.

 

5)  FDA should disclose the name and address of an entity that is inspected, the date(s) of inspection, type(s) of FDA-regulated product involved, and the final inspectional classification—Official Action Indicated (OAI), Voluntary Action Indicated (VAI), or No Action Indicated (NAI)—for inspections conducted of clinical trial investigators, Institutional Review Boards (IRB), and facilities that manufacture, process, pack, or hold an FDA-regulated product that is currently marketed.

 

6)  FDA should generate, and share with the public, information about the most common inspectional observations of objectionable conditions or practices that are made during inspections of FDA-regulated establishments and post that information online on a regular basis.

 

7)  FDA should disclose/confirm the existence or non-existence of investigational applications, which should include the name of the application sponsor, the date the application was received, the proposed indication(s) or intended use(s) of the product, and the proposed proper and/or trade name of the product, if available.

 

8)  FDA should disclose: (1) whether an investigational new drug application (IND) has been placed on hold, terminated, or withdrawn, whether an investigational device exemption (IDE) has been terminated or withdrawn and (2) if an IND has previously been placed on hold, whether and when the hold is lifted. A statement should be included that such actions may be taken for various reasons, only some of which relate to safety or effectiveness.

 

9)  FDA should disclose the fact that an NDA, NADA, ANDA, ANADA, BLA, PMA, or 510(k) application or supplement was submitted (or resubmitted) to the Agency at the time the application is received by FDA, and should include the name of the application sponsor, the date the application was received, the proposed indications or intended use of the product, and the proposed proper and/or trade name of the product, if available.

 

10) FDA should disclose that an unapproved NDA, ANDA, NADA, ANADA, BLA, or PMA, or uncleared 510(k) has been withdrawn or abandoned by the sponsor. If the drug, biological product, or device is associated with a significant safety concern, FDA should provide a brief description of the product, the use for which approval was sought or obtained, and the identified safety concern.

 

11) When an application for a designated orphan drug has been withdrawn, terminated, or abandoned, FDA should disclose, if it determines, based on its review, that the application was not withdrawn, terminated, or abandoned for safety reasons and the product, if approved, could represent a significant therapeutic advance for a rare disease. A disclaimer of FDA’s expressed views about the product should accompany the disclosure of this information.

 

12) FDA should disclose an issued refuse-to-file or complete response letter, which contains the reasons for issuing the letter, in response to an original NDA, BLA, or an efficacy supplement for an NDA or BLA at the time the refuse-to-file or complete response letter is issued.

 

13) FDA should disclose an issued refuse to approve letter, which contains the reasons for issuing the letter, in response to a NADA, or a supplemental NADA to add a new species or indication, at the time the refuse to approve letter is issued.

 

14) FDA should disclose an issued “not approvable” letter in response to a PMA for a medical device and an issued “additional information (AI)” letter in response to a 510(k) submission. Both letters must contain the reasons for issuing the letter.  

 

15) FDA should disclose relevant summary safety and effectiveness information from an investigational application, or from a pending marketing application, if the Agency concludes that disclosure is in the interest of the public health (e.g to correct misleading information about a product that is the subject of the application.)

 

16) FDA should convene a group of internal and external stakeholders to discuss the possible uses of non-summary safety and effectiveness data from product applications, the circumstances under which it would be appropriate for sponsors to disclose non-summary safety and effectiveness data from applications submitted to FDA, and if appropriate, the format and method disclosure should occur.

 

17) FDA should require companies to submit certain information to the Agency when they initiate an action to recover or correct a product that is in the chain of distribution. FDA should disclose this information when a system is set up.

18) If FDA determines that a recall is terminated (all reasonable efforts have been made to remove/correct the product), the Agency should disclose that information.

 

19) FDA should post untitled letters on the FDA Web site, and, if requested by the recipient of the letter, the response to the untitled letter, as appropriate.

 

20) FDA should keep trade secrets confidential, and where such trade secrets exist in the documents proposed for public disclosure, the Task Force supports their redaction from the documents before the documents are disclosed.

 

To advocate their report, the New England Journal of Medicine (NEJM) published an article by Dr. Sharfstein and FDA attorney Afia Asamoah, who believe that implementing some of the proposals “would accelerate the development process for medical products by allowing companies to learn from the successes and failures of other products.” In the case of orphan drugs, newly disclosed information, according to their article, “could also encourage additional investment for development of that drug or provide another company with the incentive to purchase and continue with the application.”

They also believe that “if a report that is published by a sponsor were to contain an incomplete picture about the safety or efficacy of a product, the FDA would be able to provide its analysis to contribute to the scientific discussion.”

The article also notes that further public discussions will be held on the appropriate release of certain raw data, without patient identifiers, to allow for additional study of, and new insights into, the safety and efficacy of drugs and devices.

Conclusion

 

While FDA believes transparency helps the Agency to more effectively protect and promote the public health, the administrative and financial burden associated with all of these proposals will be significant.  This kind of investment is problematic because it is not evident that any research has been conducted to show how patients, physicians, or industry will benefit from this increased transparency.  In fact the report itself states that the Task Force did not “consider the feasibility of implementing the proposals.”

 

Since FDA already makes substantial amounts of information about the regulatory process for medical products publicly available, what will these new proposals add for patients and consumers?  Will the public even be able to comprehend the information being published?  Has anyone ever studied the impact of the present public information FDA posts on patient outcomes?

 

Although it is useful that information regarding certain drugs will be made public for the benefit of public health and safety, this kind of transparency may worry many companies enough to prevent them from investing in and carrying out the riskiest kinds of research, which are usually the studies that have the most significant impact on serious diseases like cancer.

 

If transparency at FDA can foster investment in the life sciences and medical product innovation, where is the evidence of this success or progress?  Time and money spent disclosing information, instead of surveillance, reviewing and approving medical therapies will leave patients continuing to wait for new treatments.  The main goal of FDA and any researcher or health official is to produce information to the public about the safety and effectiveness of treatments in a timely manner.  Proposals contrary to this goal should be avoided, unless FDA is prepared to tell patients they must wait for a medicine because staff at the Agency was too busy disclosing information.

 

The Task Force is soliciting comments from the public on the draft proposals for 60 days. Comments can be submitted  until July 15, 2010 at www.fda.gov/transparency