FDA Debuts OpenFDA Database

paradiseLGjpg_1On June 2, 2014, the Office of Informatics and Technology Innovation (OITI) within the Food and Drug Administration (FDA) announced the launch of OpenFDA, a searchable, online public health database containing drug adverse event information compiled between October 2004 and June 2013.  The FDA press release reports that OpenFDA employs

a search-based Application Program Interface (API) to collect large amounts of existing publicly available data, offering developers the ability to search through text within that data, ranking results much like a search using Google would do.  This method then allows them to build their own applications on top of OpenFDA, giving them a large amount of flexibility to determine what types of data they would like to search and how they would like to present that data to end-users.

Currently, OpenFDA consists of approximately three million drug adverse events, though the FDA plans to expand the amount of adverse events, along with product recalls and labeling information, as they increase their capacity.

For various reasons, U.S. governmental agencies have developed open data initiatives in a number of contexts.  Perhaps the most long-standing database relevant to the FDA approval process is the clinical trials database maintained by the National Institutes of Health (NIH).  NIH has maintained the clinical trials reports and results database since 2000 as directed by Congress in legislation. Recent amendments in 2007 imposed additional requirements on NIH and clinical trial sponsors. Several other governmental initiatives to provide open data across such topics as health, agriculture, climate, and education, can be found here.

The move by FDA follows President Obama’s Executive Order in May 2013, entitled Making Open and Machine Readable the New Default for Government Information.  That Executive Order directs executive departments and agencies to implement measures to support an open data policy in their operations and missions.  The memorandum detailing this policy “requires agencies to collect or create information in a way that supports downstream information processing and dissemination activities. This includes using machine readable and open formats, data standards, and common core and extensible metadata for all new information creation and collection efforts.”  In addition, “it involves agencies building or modernizing information systems in a way that maximizes interoperability and information accessibility, maintains internal and external data asset inventories, enhances information safeguards, and clarifies information management responsibilities.”  President Obama has touted an Open Government Directive focusing on transparency, participation, and collaboration since taking office in 2009.

Researchers, web developers, and members of the public praise OpenFDA, citing numerous challenges to access and interpretation of adverse event information in the past.  These challenges include lengthy Freedom of Information Act request turnaround times, a lack of uniformity in quarterly bulk reports distributed by the FDA making them difficult to decipher, and no ability to search across data in the FDA adverse event reporting system.  A GCN article notes that with OpenFDA “users can find what they’re looking for by typing drug names, QR or UPC codes or even reaction symptoms. Misspellings will likely still return an accurate result because each query is given a score that is similar to how search engines operate.”  TechRepublic provides a helpful overview of the technical features of OpenFDA here.

Many sources urge that the new database will maximize the return on the adverse event data and enable the private sector to innovate in an area where the FDA has limited resources.  In fact, one application resulting from OpenFDA has already sprung up.  ResearchAE, developed by Social Health Insights, is a query interface allowing users to search adverse drug effects by multiple classifications, such as date, location, patient age, drug name, manufacturer, and reaction.  HealthCare IT highlights this new application here.

While OpenFDA has been met with widespread enthusiasm, a few concerns have arisen about the availability and use of the information.  Some have questioned the security of the information on OpenFDA.  However, the FDA assures that all identifying information has been removed from the adverse event data available in the online database.  The Chief Health Informatics Officer within OITI, Dr. Taha Kass-Hout, stated “we will not release any data that could be used to identify individuals or reveal other private information.”  Others, including pharmaceutical manufacturers, have questioned whether the public and other entities will be able to comprehend the data without causing undue turmoil in the market.  To that criticism, Kass-Hout responds that the FDA “will be correcting misinterpretations” of the data.


The FDA as Researcher: Empirical Research on the Impact of Potential Policy Reforms

coleman_carl_lg2In addition to being one of the primary federal agencies responsible for regulating health-related research, the FDA also sometimes undertakes research in its own right, including studies designed to assess the merits of potential policy reforms.   For example, in recent years, the FDA has conducted studies on subjects such as how consumers use and understand nutrition label facts, the extent to which in-vitro laboratory testing predicts how well new medical devices will perform in clinical trials, and the impact of picture warnings on smokers’ intention to quit.  In the past few months, FDA has announced its intention to undertake two studies related to the provision of information in prescription drug advertisements, both of which could have significant implications for the agency’s advertising regulations.

The first of the FDA’s prescription drug advertising studies, announced in February, responds to two ongoing – and seemingly contradictory – concerns about the nature of the risk information presented in direct-to-consumer (DTC) drug ads.  On the one hand, concerns have been raised that the risk information presented in DTC ads is too long, resulting in “reduced consumer comprehension, minimization of important risk information and, potentially, therapeutic noncompliance due to fear of side effects.”  On the other hand, there are also concerns “that DTC TV ads do not include adequate risk information or leave out important information.”

The FDA’s hypothesis is that a better approach to risk disclosure would be to limit risk disclosures in DTC TV ads to those risks “that are serious and actionable” and then to “include a disclosure to alert consumers that there are other product risks not included in the ad.”  However, rather than simply amending the DTC regulations to incorporate this strategy, the FDA has decided to first investigate its likely effectiveness by conducting empirical research.

To that end, FDA proposes to conduct online surveys of consumers who have self-identified as having been diagnosed with one of three possible medical conditions.  Participants will be randomly assigned to view one of four possible versions of DTC drug ads, which will vary in the nature of the risk disclosures and the presence or absence of an additional statement regarding the existence of non-disclosed risks.  After viewing the ads, participants will be asked questions designed to assess their perceptions and understanding.

 The second study, announced last week, involves a similar approach to evaluating the impact of price comparison information in prescription drug ads – in this case, both DTC ads and ads directed at healthcare professionals.  The goal of this study is to evaluate whether ads that contain price comparisons lead viewers to believe “that the products are interchangeable and that price is the main factor to consider,” and, if so, whether this perception can be corrected by the inclusion of additional “contextual information about efficacy or safety,” as existing regulations now require.

Unlike the risk disclosure study, in which the FDA has already formed a hypothesis and is seeking to evaluate it, the price comparison study does not appear to be hypothesis-driven.  Instead, the stated goal is simply to “investigate, through empirical research, the impact of price comparison information and additional contextual information on prescription drug product perceptions.”

The FDA has solicited public comments on both studies.  The requests for comments were issued pursuant to the Paperwork Reduction Act (PRA), which requires agencies to provide a 60-day notice and comment period before any proposed “collection of information,” following which it must submit its proposed information collection to the Office of Management and Budget for approval.  While the focus of the PRA notice-and-comment period is on minimizing the burden of information-collection activities, the FDA has also invited comments on the “quality, utility, and clarity of the information to be collected.”

It is too early to tell what kind of comments will be received on the price comparison study, but comments on the risk disclosure study have already been submitted.  Many of the comments were supportive, including those submitted by industry.  However, the advocacy group Consumers Union expressed strong opposition to the study.  In addition to suggesting that the study design was methodologically flawed, Consumers Union maintained that the study was “unnecessary and could lead to consumers getting less information about a drug than is currently required.”  It argued that “[a]ny limitations on the information contained in DTC ads would be an inadequate portrayal of a drug’s safety.”

While other consumer groups raised concerns about specific aspects of the study design, they did not join Consumers Union’s call for FDA to abandon the study entirely.  Instead, these groups “applaud[ed] FDA’s efforts to clearly and effectively communicate risks and benefits to consumers.”  These groups seem to recognize that, when it comes to risk disclosure, more is not necessarily better.  As has been pointed out in the context of securities law, too much disclosure can lead to the problem of “information overload,” which occurs when individuals “have so much information available to them that they will sometimes be unable to distinguish what is important from what is not.”  The goal for public policy should not be to ensure that consumers have access to information for its own sake, but rather to ensure that they are in a position to make informed decisions based on an accurate understanding of the most important risks at stake.

In any case, the best way to determine whether limiting risk disclosures helps or hurts consumers is to study the question empirically – which is exactly what the FDA proposes to do. The agency should be commended for its efforts to develop an evidence basis for public policy.  Its approach is consistent with recent calls for subjecting regulatory policies to ongoing empirical evaluation, and is a model that other agencies would do well to emulate.


Potential Effects of Clinical Trial Data Sharing on Biopharmaceutical Innovation

P18We are very pleased to welcome Dana Darst, a Master of Science in Jurisprudence candidate in Health Law and Intellectual Property Law here at Seton Hall, to the blog today.

In recent years, biopharmaceutical research and development organizations have established partnerships with academic institutions and start-up biotechnology companies to drive external innovation, complementary to their own in-house advancements in life sciences.  Companies such as Pfizer, Johnson & Johnson and Bayer have opened innovation centers of excellence globally, in start-up biotechnology- and academia-rich hubs such as Boston, San Francisco and Shanghai, as part of an effort to accelerate new product development and commercialization.  

More recently, the industry has commenced driving innovation via sharing clinical study protocols and patient-level treatment information at the request of qualified external researchers.  An objective of this undertaking is to enhance public health via data transparency.  This may increase efficiencies by helping researchers avoid unnecessary use of resources for new studies, when relevant clinical outcomes data exists from previous studies.  In addition, it may reduce risks for future research subjects.

On January 30, 2014, Janssen Research and Development, LLC (a Johnson & Johnson subsidiary) and The Yale School of Medicine’s Open Data Access Project (YODA) announced a pioneering partnership model for sharing clinical trial data.  Under their agreement, YODA will review all clinical trial data requests on Janssen’s behalf, as an independent third-party.  In a press release, J&J’s Chief Medical Officer, Joanne Waldstreicher, MD, stated that their collaboration will “[e]nsure that each and every request for access to [their] pharmaceutical clinical data is reviewed objectively and independently.”  She further stated that “[t]his represents a new standard for responsible, independent clinical data sharing.”  Other biopharmaceutical companies sharing clinical trial data do so by reviewing data requests directly as they are received from qualified external researchers.  Also, some have voluntarily adopted the Principles For Responsible Clinical Trial Data Sharing, jointly published by the Pharmaceutical Research Manufacturers of America (PhRMA) and European Federation of Pharmaceutical Industries and Associations (EFPIA), and implemented on January 1, 2014. 

Under the PhRMA-EFPIA guidelines, “Biopharmaceutical companies are committed to enhancing public health through responsible sharing of clinical trial data in a manner that is consistent with the following Principles”: (1) Safeguarding the privacy of patients, (2) Respecting the integrity of national regulatory systems, and (3) Maintaining incentives for biomedical research.  The guidelines provide a framework for life sciences companies to request patient-level data and study protocols.  Additionally, the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) have proposed policies to increase transparency of clinical trial data.  As Carl Coleman discussed here, both agencies have addressed the importance of patient and study de-identification.

So, what potential implications might clinical trial data sharing have on biopharmaceutical innovation? The Institute of Medicine (IOM) et al. recently published a report, Discussion Framework for Clinical Trial Data Sharing: Guiding Principles, Elements and Activities, as a framework for further discussion and public comment on how data from clinical trials might best be shared.  It provides four guiding principles for consideration which include (1) respecting individual participants, (2) maximizing benefits to participants in clinical trials and to society, while minimizing harm, (3) increasing public trust in clinical trials, and (4) carrying out sharing of clinical trial data in a manner that enhances fairness. 

The report does not provide conclusions or recommendations, which are expected to be developed and published approximately 17-months from the project’s start in August 2013. However, the IOM Committee, which includes a diverse group of representatives from government, charitable foundations, academia, healthcare institutions and private industry, has posed several potential implications of trial data sharing for consideration. 

Potential Benefits

From a societal perspective, sharing clinical trial data could increase accuracy, reduce bias and provide a more comprehensive picture of a drug’s benefits and risks.  In addition, data sharing could potentially improve efficiency and safety of the clinical research process.  For example, it could reduce potential duplication of efforts and costs of future studies, and help to avoid unnecessary harm to patients.  Furthermore, it may provide additional information to healthcare professionals and patients that can be utilized to make better informed decisions. 

Potential Harms

Alternatively, data sharing could lead to invasions of patient privacy or breaches of confidentiality, which may ultimately harm participants, either socially or economically.  Moreover, it could reduce incentives for study sponsors to invest their limited resources (e.g. time, budget, FTEs) on additional trials, which could ultimately inhibit innovation.  As the IOM Committee explains:

For example, data sharing might allow confidential commercial information (CCI) to be discerned from the data.  Competitors might use shared data to seek regulatory approval of competing products in countries that do not recognize data exclusivity periods or that do not grant patents for certain types of research. 


Sharing clinical study protocols and patient-level trial data could have benefits for society and healthcare, which outweigh the risks.  The IOM is planning to include an analysis of risks and benefits in their final report.  As academic, life sciences and start-up biotech entities increasingly share industry-driven trial data, a prudential approach should be taken to protect the confidentiality and intellectual property of all stakeholders involved.  Specifically, data should be adequately redacted prior to disclosure to eliminate confidential information—as recommended by the EMA and U.S. FDA.  Biopharmaceutical Innovation is driven by authors and inventors that rely on exclusive, protected rights granted for limited times.  As the IOM committee works toward establishing guidelines, adherence to their guiding principles to address these protected rights will be vital.  

To obtain additional information or provide public comments on the IOM project, visit their website at: http://www8.nationalacademies.org/cp/projectview.aspx?key=49578.


War on Disclosure: Recent Fronts in Health Care

June 5, 2012 by · 2 Comments
Filed under: Transparency 

thrilling_detective_october_1935Corporations are at war with disclosure in many important fields.  Two notable fronts have recently opened in health care:

1) Fracking processes have become highly controversial because secret chemicals may end up compromising water supplies.  Pennsylvania has now limited doctors’ ability to speak about their concerns:

Under a new law, doctors in Pennsylvania can access information about chemicals used in natural gas extraction—but they won’t be able to share it with their patients. . . .Pennsylvania law states that companies must disclose the identity and amount of any chemicals used in fracking fluids to any health professional that requests that information in order to diagnosis or treat a patient that may have been exposed to a hazardous chemical. But the provision in the new bill requires those health professionals to sign a confidentiality agreement stating that they will not disclose that information to anyone else—not even the person they’re trying to treat.

Protection of property rights uber alles appears to be the guiding principle here.  If only the doctors wanted to market drugs, maybe their free speech rights would trump the frackers’ trade secrecy privileges.

2) FDA User-Fee Bills recently approved by the House and Senate could seriously limit access to data about drugs.  The House bill is particularly worrisome:

The Food and Drug Administration Reform Act of 2012, H.R.5651 . . . would keep potentially important health and safety information away from the public. Section 812 would, according to a letter to leaders of the House Oversight and Government Reform Committee penned by several [advocacy] groups, deny the public access to information relating to drugs obtained by the U.S. Food and Drug Administration (FDA) from any government agency — local, state, federal, or foreign — if that agency has requested that the information be kept confidential.

If that House provision survives the conference committee, there will be troubling implications for US patients and research subjects abroad.


Physician Payment Sunshine Act Proposed Regulations Out

January 3, 2012 by · 1 Comment
Filed under: Bioethics, Drugs & Devices, Transparency 

boozang123CMS has published proposed rules for its implementation of the Physician Payment Sunshine Act (SUNSHINE ACT or Act), which was enacted by Congress as part of the 2010 Patient Protection and Affordable Care Act.  In short, the SUNSHINE ACT requires life science companies to report annually to CMS their conferral of anything of value, whether it be payment for services or a dinner, in connection with a particular product of the paying company.  By requiring CMS to post the information on its website, the Act seeks to ensure that interested patients become aware of physicians’ conflicts of interest that could affect their prescription of a branded drug or choice of a specific medical device.

The SUNSHINE ACT represents another example of the transparency movement, which has had varying degrees of success in either changing the behavior of the parties subject to disclosure, and/or enabling consumers to make better decisions based upon their access to the disclosed information.  It is likely that the SUNSHINE ACT will impact physicians and manufacturers’ behavior more than it will enlighten consumers about conflicts of interest.  Some physicians will simply conclude that accepting certain gifts or benefits from pharmaceutical or medical device companies isn’t worth having their names on the CMS website.  Some companies have already discovered that they haven’t necessarily reaped the value of the costs of gifting many physicians, or that the cost of recording certain activities simply isn’t worth the return on investment.  Unquestionably, certain transactions will continue to be valuable to both physician and company, and will continue.

It is unlikely that most patients will access the information either before or after a physician visit, or know what to do with the information even if they discover that their physician has an equity interest in the knee she plans to use in next week’s surgery – does such a close relationship with the knee manufacturer signal that the physician is great, or that something nefarious is going on?  The information is likely to be used by consumer watchdog groups, as well as hospital formulary committees and medical school deans interested in knowing the sources and amounts of outside income being earned by faculty.  Divorce attorneys are likely to find the information useful if their client’s soon-to-be ex-spouse hasn’t reported significant pharma consulting fees as income.

CMS rulemaking is behind schedule, thereby delaying the SUNSHINE ACT’s implementation.  It is likely, however, that the ultimate rules will still require that 2012 data be submitted, even if not by the deadline originally contemplated by Congress.

The statute requires manufacturers of drugs, devices, biological or medical supplies covered by Medicare, Medicaid or the Children’s Health Insurance Program (CHIP) (“applicable manufacturers”) to report annually to HHS payments or transfers of value to physicians and teaching hospitals (“covered recipients”).  Failure to comply will result in Civil Monetary Penalties.  HHS, in turn, must publish this information on a public web site which is searchable, downloadable and able to be aggregated.  Compliance with the SUNSHINE ACT’s reporting requirements does not exempt applicable manufacturers from application of fraud, waste and abuse laws.

Applicable Manufacturer

The proposed rule merges the SUNSHINE ACT definition of “manufacturer of a covered drug, device, biological, or medical supply”[1] with the statutory section clarifying that the entity covered by the SUNSHINE ACT must be “operating in the United States, or in a territory, possession, or commonwealth of the United States”[2] to define applicable manufacturer as one

(1)    Engaged in the production, preparation, propagation, compounding, or conversion of a covered drug, device, biological, or medical supply for sale or distribution in the United States, or in a territory, possession, or commonwealth of the United States; or

(2)    Under common ownership with an entity in paragraph (1) of this definition, which provides assistance or support to such entity with respect to the production, preparation, propagation, compounding, conversion, marketing, promotion, sale, or distribution of a covered drug, device, biological, or medical supply for the sale or distribution in the United States, or in a territory, possession, or commonwealth of the United States.

The operative activity that invokes statutory coverage, then, is sale of a product in the United States, as opposed to where the product is produced, or where the entity is located or incorporated. Pursuant to the rationale that risks inhere in conflicts of interest irrespective of where the manufacturer is located if the product is sold in the United States, any entity under common ownership with the manufacturer that is involved in the production, distribution or sale of at least one covered product in the United States must report all payments and conferral of value upon covered recipients. Further, as proposed, the product sponsor (i.e., the entity that obtained FDA approval) is subject to the reporting requirement, even if the sponsor is not involved in the manufacture of the covered product.  CMS is considering alternative interpretations of the common ownership concept.

Covered Drug, Device, Biological, or Medical Supply (“covered product”)

The SUNSHINE ACT focuses upon those products for which Medicare, Medicaid and CHIP pay.  This is relatively straightforward in many contexts, but CMS seeks to ensure that it captures situations where such products are part of a composite rate payment, such as the inpatient or outpatient hospital reimbursement, or the end-stage renal disease prospective payment system.  As such, CMS proposes to define “covered drug, device, biological, or medical supply” as:

Any drug, device, biological, or medical supply for which payment is available under Title XVIII of the Act or under a State plan under title XIX or XXI (or a waiver of such plan), either separately, as part of a fee schedule payment, or as part of a composite payment rate (for example, the hospital inpatient prospective payment system or the hospital outpatient prospective payment system).  With respect to a drug or biological, this definition is limited to those drug and biological products that, by law, require a prescription to be dispensed.  With respect to a device or medical supply, this definition is limited to those devices (including medical supplies) that, by law, require premarket approval by or premarket notification to the Food and Drug Administration.

CMS seeks comments on its plan to exclude from the scope of regulation those manufacturers who produce and sell only over the counter (OTC) products.  More specifically, this exemption would not extend to a manufacturer who sells even one prescription product who is otherwise subject to the reporting requirements of the SUNSHINE ACT.  Similarly, CMS seeks to interpret the SUNSHINE ACT to cover only those medical devices that require premarket approval, on the theory that this is the segment of the market most likely to have extensive provider relationships.  If a device manufacturer produces a single product that requires pre-market approval, it would have to report all payments and conferrals of value to covered recipients.

Covered Recipients

The SUNSHINE ACT defines “covered recipients” as (1) a physician, other than a physician who is an employee of an applicable manufacturer; or (2) a teaching hospital.   The term physician includes both doctors of medicine and osteopathy as well as podiatrists, optometrists and licensed chiropractors. CMS interprets the statute to include within its scope those who act on behalf of covered recipients.  Teaching hospital is not defined by the statute; CMS seeks comments on its proposal to identify such entities by virtue of their receipt of Medicare graduate medical education funds. CMS will publish this list annually on its website for manufacturers’ reference.

CMS plans to utilize the National Plan & Provider Enumeration System, which it maintains on its website, to collect the data regarding covered recipients required by the SUNSHINE ACT: covered recipient’s name and business address, and, for physicians, the National Provider Identifier and specialty.

Payments or Other Transfers of Value

The report must also include the date, form (i.e., cash, stock, ownership interest), nature (i.e., education, research, consulting fees, food) and amount of payment, and the market name of the product associated with the payment.  CMS continues to consider how to handle payments made to a single covered recipient related to multiple products.  CMS seeks to generate data in a form most easily understood by consumers.

The statutory definition requires such conferrals to be reported irrespective of whether they were requested by the physician or hospital and includes those made by third parties as long as the applicable manufacturer knows the identity of the covered recipient. CMS proposes that payments made through a group practice be reported under the specific recipient physician’s name.  If a physician requests the conferral to be directed to another physician or entity, the manufacturer should report the conferral under the requesting physician’s name as well as the name of the actual recipient.

Charitable contributions by an applicable manufacturer to, at the request of, or on behalf of a covered recipient are reportable.

The SUNSHINE ACT excludes from its reporting requirement the following payments:

  • Transfers of value less than $10, unless the aggregated amount exceeds $100 in a calendar year
  • Product samples not intended to be sold that are intended for patient use
  • Educational materials that directly benefit patients or are intended for patient use
  • The loan of a covered device for a period not to exceed 90 days, to permit evaluation
  • Items or services provided under a contractual warranty
  • A transfer of value or payment to a covered recipient when that person is receiving the conferral in his/her capacity as a patient
  • Discounts, including rebates
  • In-kind items used for the provision of charity care
  • A dividend or profit distribution from ownership or investment interest in a publicly traded security or mutual fund
  • Self-insurance payments to covered employees by an applicable manufacturer
  • Non-medical services
  • Transfers of value made by third parties where the applicable manufacturer is unaware of the identity of the covered individual

CMS will be moving rapidly to respond to comments and finalize these rules, which will likely involve changes from the discussion here.  State laws that pre-date the Act are pre-empted to the extent that they require reporting of the same information, which leaves them the discretion to retain those reporting requirements that are not redundant.  States seeking to impose as much of a burden on manufacturers as possible are likely to retain their individualized reporting requirements, others may find the costs not worth the benefits now that the feds have finally stepped in.

[1] Section 1128G(e)(9).

[2] Subsection (e)(2) further clarifies that the entity covered by the SUNSHINE ACT must be “operating in the United States, or in a territory, possession, or commonwealth of the United States.”


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