We are focused on two key areas in ensuring the transparency of clinical research and development on the drugs and medical devices that millions of Americans depend on a daily basis: enhancing government enforcement; and overcoming industry resistance.
Enhancing Government Enforcement
Our agenda includes research, policy, and legal work to increase compliance with existing transparency obligations. The U.S. government has many rules and regulations to ensure clinical trial transparency, but they are not being enforced. CRIT will characterize compliance with these rules and regulations by companies, academic institutions and investigators. We will work to establish an environment where noncompliance is not tolerated, and enforcement is promoted.
Overcoming Industry Resistance
Our agenda targets the key arguments that industry uses to resist transparency, promoting structural change in public and private drug litigation. The pharmaceutical and device industries put forward many reasons justifying their inability to divulge clinical trial results. Their most successful objections relate to the need to protect patient privacy and confidential commercial information (CCI). Patient privacy must be protected, but existing practices allow data to be available to researchers while protecting patient privacy. CCI objections are typically unfounded and pose a significant banier to obtaining useful data from requests to government agencies and litigation. We will work to encourage structural change in litigation policies, encouraging greater transparency.
Kapczynski A. The Lochnerized First Amendment and the FDA: Toward a More Democratic Political Economy. Response to the Columbia Law Review's 2018 Symposium. Columbia Law Review Online. 2018;118:179-206.
Puthumana J, Wallach JD, Ross JS. Clinical Trial Evidence Supporting FDA Approval of Drugs Granted Breakthrough Therapy Designation. JAMA. 2018;320(3):301-303.
Puthumana J, Miller JE, Kim J, Ross JS. Availability of Investigational Medicines Through the US Food and Drug Administration's Expanded Access and Compassionate Use Programs. JAMA Network Open. 2018;1(2):e180283
Wallach JD, Ross JS, Naci H. The US Food and Drug Administration's Expedited Approval Programs: Evidentiary Standards, Regulatory Trade-offs, and Potential Improvements. Clinical Trials. 2018;15(3):219 - 229.
Wallach JD, Ross JS, Naci H. The US Food and Drug Administration's Expedited Approval Programs: Addressing Premarket Flexibility With Enhanced Postmarket Evidence Generation. Clinical Trials. 2018;15(3):243-246.
Wallach JD, Egilman AC, Dhruva SS, et al. Postmarket studies required by the US Food and Drug Administration for new drugs and biologics approved between 2009 and 2012: cross sectional analysis. BMJ. 2018;361:k2031.
Wallach JD, Ciani O, Pease AM, et al. Comparison of Treatment Effect Sizes from Pivotal and Postapproval Trials of Novel Therapeutics Approved by the FDA Based on Surrogate Markers of Disease: A Meta-Epidemiological Study. BMC Medicine. 2018;16(1):45.
Klara, K, Kim, J, Ross JS (2018) Direct-to-Consumer Broadcast Advertisements for Pharmaceuticals: Off-Label Promotion and Adherence to FDA Guidelines. J Gen Intern Med 2018;33(5):651-658
Wallach JD, Ross JS. Gabapentin Approvals, Off-Label Use, and Lessons for Postmarketing Evaluation Efforts. JAMA. 2018;319(8):776–778.
Egilman AC, Wallach JD, Ross JS, Dhruva SS. Medicare Spending and Potential Savings on Brand-Name Drugs With Available Generic Substitutes Excluded by 2 Large Pharmacy Benefit Managers, 2012 Through 2015. JAMA Intern Med. 178(4):567-569
Kapczynski A, Kim J. Clinical Trial Transparency: The FDA Should and Can Do More. The Journal of Law, Medicine & Ethics. 2018;45(2_suppl):33-38.
Sharfstein JM, Miller JD, Davis AL, Ross, JS, McCarthy ME, Smith B, Chaudry A, Alexander GC, Kesselheim AS. Blueprint for Transparency at the U.S. Food and Drug Administration: Recommendations to Advance the Development of Safe and Effective Medical Products. The Journal of Law, Medicine & Ethics 2018;45(2_suppl):7-23.
Wallach JD, Egilman AC, Gopal AD, Swami N, Krumholz H, Ross JS. Biomedical Journal Speed and Efficiency: A Cross-sectional Pilot Survey of Author Experiences. Research Integrity and Peer Review. 2018;3(1).
Wallach JD, Gonsalves GS, Ross JS. Research, regulatory, and clinical decision-making: the importance of scientific integrity. J Clin Epidemiol. 2018;93:88-93.
Kim J, Kapczynski A. Promotion of Drugs for Off-label Uses: The US Food and Drug Administration at a Crossroads. JAMA Intern Med. 2017;177(2):157-158.
Kim J, Ross JS, Kapczynski A. Pediatric Exclusivity and Regulatory Authority: Implications of Amgen v HHS. JAMA. 2017;319(1):21-22.
Krumholz HM, Kim J. Data Escrow and Clinical Trial Transparency. Ann Intern Med. 2017;166(12):893-894.
We co-published a policy paper, Clinical Trial Transparency: A Guide for Policy Makers, along with Transparency International, Cochrane and Transparimed, written by Till Bruckner, founder of Transparimed.
We released a policy paper on November 3, 2017, Promoting Transparency in Clinical Research: Why and How, edited by Margaret E. McCarthy, Jeanie Kim and Joseph S. Ross. We focus on the harms caused by lack of transparency, the benefits of increased clinical trial transparency and data sharing for researchers, regulators, clinicians, payers, and policy makers, and the current status of transparency efforts.
We released French, Spanish, and Portuguese versions of What's in Your Medicine Cabinet? Ensuring the Safety and Efficacy of Prescription Drugs, Biologics and Medical Devices in the United States, now in its third edition.
We released a white paper on June 20, 2017,What’s in Your Medicine Cabinet? Ensuring the Safety and Efficacy of Prescription Drugs, Biologics and Medical Devices in the United States, edited by Margaret E. McCarthy and Gregg Gonsalves. We focus on federal regulation of medical products by the U.S. Food and Drug Administration (FDA), but also discuss the courts’ and Congress’ influence on the safety and efficacy of drugs, devices and biologics, and the critical role of industry in the development both of new products and of the evidence base supporting their use.
National Academies Committee on Return of Research Results to Participants
July 2017 - July 2018
Gregory Gonsalves participated in an ad hoc committee of the National Academies of Sciences, Engineering, and Medicine that examined the return of research results to clinical trial participants. The committee developed a consensus report, Returning Individual Research Results to Participants, Guidance for a New Research Paradigm, released July 10, 2018. The reports makes 12 recommendations that (1) support decision making regarding the return of results on a study-by-study basis, (2) promote high-quality individual research results, (3) foster participant understanding of individual research results, and (4) revise and harmonize current regulations.
FDA Transparency Working Group
Summer 2016 – January 2018
Joseph S. Ross and Margaret E. McCarthy participated in the FDA Transparency Working Group. Researchers from Johns Hopkins Bloomberg School of Public Health, Brigham and Women’s Hospital/Harvard Medical School, Yale Medical School and Yale Law School wrote the Blueprint for Transparency at the U.S. Food and Drug Administration. The Blueprint was published in a special issue of the Journal of Law, Medicine and Ethics, along with invited commentaries. A conference to discuss the release of the Blueprint was held on January 16, 2018, and the webcast can be viewed here.
Commentary on the NIH Budget Process
Gregg Gonsalves and Harlan M. Krumholz wrote an opinion piece, Taking a Ride on the NIH Budget Rollercoaster, for Stat News about the need for adequate funding for the National Institutes of Health.
Commentary on the Need for a Strong FDA
Joseph S. Ross and Harlan M. Krumholz wrote a commentary, Taking Shortcuts in Drug Testing Can Put Patients At Risk for National Public Radio.
We submitted public comments on the NIH’s “Proposed Provisions for Draft NIH Data Management and Sharing Policy.” In our comments, we support the NIH proposal to extend the requirement for sharing data to all NIH-funded research regardless of regardless of annual direct cost amount, and we urge the NIH to require that proposals include a budget for implementation of the data preservation and access requirements, as well as final preparation of the data for archiving. Finally, we urge the NIH to create data repositories across all of its institutes.
We submitted public comments supporting proposed FDA regulations regarding FOIA that implement the requirements of 2016 and earlier FOIA amendments. We encourage the FDA to go beyond the regulations in adding staff to ensure that FOIA requests are fulfilled more quickly, and to promptly comply with the requirement that information requested by 3 requestors be placed on the FDA website once at least one request has been fulfilled.
We submitted public comments on an FDA draft guidance on enforcement of penalties for failure to comply with the registration and reporting requirements to the ClinicalTrials.gov data bank. Our comments support enforcement efforts by the FDA. We recommend modifications to the guidance to clarify the mandatory nature of the FDA's responsibility to monitor compliance, to expand monitoring beyond inspections carried on through the BioResearch Monitoring Program, and to specify the FDA's obligation to work cooperatively with the NIH to enforce the registration and reporting requirements.
We submitted public comments on a proposed Environmental Protection Agency (EPA) regulation that could limit the EPA's ability to rely on scientific studies for which the underlying data and models were not made public. Responsible data-sharing policies adopted by other federal agencies require that study results and research plans be made public, and that data be shared with other researchers through a data archive, but do not require that individual-level underlying data and models be made available to the public. We urged the EPA to withdraw the proposed regulation.
We submitted public comments on a draft guidance on public release of clinical information, which describes the implementation of data sharing regulations proposed by Health Canada. Our comments support Health Canada's proposed public release of clinical information. We made recommendations to increase the types of documents and data that would be shared, and to limit exceptions to release.
We submitted public comments on data sharing regulations proposed by Health Canada. Our comments support Health Canada's proposed regulations. We made recommendations to increase the types of documents and data that would be shared, and to limit exceptions to release.
CRIT submitted public comments in response to an FDA draft guidance on clarifying orphan drug designation of drugs and biologics for pediatric subpopulations of common diseases. We agreed with the FDA’s draft guidance, designed to close the loophole which allowed sponsors to obtain orphan drug designation for pediatric subpopulations of common diseases, while exempting them from requirements to do pediatric studies.
CRIT submitted public comments to an FDA notice that the agency will delay implementing a final rule defining “intended uses” of drugs and devices. We urged the FDA to implement the final rule, to require adequate labeling, and to continue to enforce prohibitions against off label marketing.
We submitted public comments in response to a request for public comments from Health Canada. Our comments support Health Canada's proposal to publicly release clinical information in drug submissions and medical device applications. We made recommendations to increase the types of documents and data that would be shared.
Testimony at FDA Hearing on Off-Label Marketing
Amy Kapczynski, Jeanie Kim, and Margaret E. McCarthy, presented testimony at an FDA Hearing on Manufacturer Communications Regarding Unapproved Uses of Approved or Cleared Medical Products on November 10, 2016. Watch their testimony.
Public Comments on Use of Real World Evidence in the Medical Device Context
CRIT submitted public comments to an FDA draft guidance on the use of real world evidence in the medical device context. We urged the FDA not to lower evidentiary standards for device evaluation and suggested appropriate uses for high quality real world evidence.
A Primer on Clinical Trials Issues
Audrey Zhang, an NYU Medical student working with the YODA project developed a guide to the FDA approval process for medical products.
Request to European Medicines Agency
In November 2016, we submitted a request to the European Medicines Agency (EMA) for all data related to Sovaldi and Harvoni two Hepatitis C drugs. This effort was undertaken on behalf of the Global Health Justice Partnership (GHJP) and Treatment Action Group (TAG) and is underway. We are still receiving documents from the EMA, including clinical study reports.
Simple FOIA Project
CRIT staff, working with the Media Freedom & Information Access Clinic (MFIA), draft and submit FOIA requests in coordination with researchers. The requests are designed to fall on the FDA's simple FOIA track, where requested documents are easily found and typically provided within 30 days. Researchers are then able to use the documents in ongoing research projects designed for peer reviewed publication.
CRIT assisted Dr. G. Caleb Alexander, Co-Director of the Center for Drug Safety and Effectiveness at the Johns Hopkins Bloomberg School of Public Health, to obtain documents from the FDA regarding the class-wide Risk Evaluation and Mitigation Strategy (REMS) for Transmucosal Immediate-Release Fentanyls (TIRFs), very strong opioids approved only for use for breakthrough cancer pain in opioid-tolerant patients. This information provided the basis of August 2018 testimony before an FDA Advisory Committee indicating that despite the REMS, as many as 51% of patients prescribed TIRFs were not opioid tolerant, and that evidence suggested that many receiving TIRF prescriptions did not have cancer. Some of the documents released were made available by the New York Times in conjunction with an article.
CRIT works with attorneys from the Media Freedom & Information Access Clinic (MFIA) to pursue key litigation advancing transparency and integrity.
ClinicalTrials.gov Enforcement Litigation
Charles Seife and Peter Lurie v. U.S. Department of Health and Human Services
On December 7, 2018, Yale CRIT attorneys working with Yale’s MFIA student clinic filed suit on behalf of Charles Seife and Dr. Peter Lurie to demand that NIH, FDA, and HHS comply with their legal obligations to notify the public of failure to report clinical trial results on ClinicalTrials.gov.
Collaboration for Research Integrity and Transparency v. U.S. Department of Health and Human Services, National Institutes of Health, and Food and Drug Administration
The Media Freedom and Information Access Clinic (MFIA) filed a complaint on behalf of CRIT, urging a federal district court in Connecticut to compel the Department of Health and Human Services (HHS), the National Institutes of Health (NIH), and the Food and Drug Administration (FDA) to comply with their legal obligations to notify the public of researchers' failure to report clinical trial results on ClinicalTrials.gov.
Charles Seife v. Food and Drug Administration and Department of Health and Human Services (ongoing)
CRIT, in collaboration with attorneys from the Media Freedom & Information Access Clinic (MFIA), assisted an investigative journalist and NYU journalism professor, Charles Seife, in filing a Freedom of Information Act (FOIA) request to the FDA for documents and data regarding the approval of Exondys 51 (eteplirsen) for Duchenne Muscular Dystrophy. When the requested documents were not received, attorneys from MFIA Clinic filed suit.
MFIA attorneys filed a motion for partial summary judgment, challenging the FDA's denial of an expedited processing request. On July 27, 2017, pursuant to a court order, the FDA stipulated to an expedited schedule for release of the requested information. Throughout the second half of 2017, the FDA produced thousands of pages of requested documents. However, some of the documents were heavily redacted, and the FDA continues to withhold other key documents, alleging that they contain confidential commercial information submitted by Sarepta. In early 2018, Seife published an in-depth investigative piece in Scientific American, "Is the FDA Withholding Data about a Controversial Drug to Protect its Manufacturer?" based on what he has learned from the lawsuit.
The FDA and Sarepta Therapeutics moved for summary judgment, arguing that the withheld documents should not be released to Charles Seife. MFIA attorneys cross-moved for summary judgment, arguing that the withheld documents should be provided to Charles Seife. MFIA attorneys also moved to stike the testimony of one of Sarepta's employees.
The Media Freedom & Information Access Clinic (MFIA) continues to litigate the case. Key documents in the case are below.
Complaint and Answers
Plaintiff's Motion for Partial Summary Judgment Regarding Expedited Processing
- Plaintiff's Motion for Partial Summary Judgment Regarding Expedited Processing
- Stipulation and Order
Motions for Summary Judgment
- Sarepta's Motion for Summary Judgment
- FDA's Memorandum of Law in Support of Motion for Summary Judgment
- Plaintiff's Cross Motion for Summary Judgment
- Plaintiff's Motion to Strike
- FDA's Combined Memorandum of Law
- Sarepta's Response and Reply Regarding Summary Judgment
- Sarepta's Memorandum of Law in Opposition to Motion to Strike
- Plaintiff's Reply Memorandum of Law
Freedom of Information Act Litigation, Treatment Action Group and Global Health Justice Partnership, v. Food and Drug Administration and Department of Health and Human Services
As part of efforts to make the clinical data submitted to the Food and Drug Administration (FDA) publicly transparent and accessible, the Global Health Justice Partnership (GHJP) and Treatment Action Group (TAG) submitted a Freedom of Information Act (FOIA) request to the FDA for documents and data regarding 2 drugs used to treat Hepatitis C, Sovaldi and Harvoni. When the requested documents were not received, TAG and GHJP filed suit. CRIT, in collaboration with attorneys from the Media Freedom & Information Access Clinic (MFIA), litigated the case in federal court. We received trial protocols, clinical study reports and adverse event reports as well as other useful documents from the FDA.
Amicus Brief in the Matter of Avandia Marketing, Sales Practices & Products Liability Litigation
CRIT, in collaboration with Public Justice, PC, and the Media Freedom and Information Access Clinic (part of the Abrams Institute for Freedom of Expression at Yale), filed an amicus brief in the Matter of Avandia Marketing, Sales Practices & Products Liability Litigation, United Food and Commercial Workers Local 1776 and Participating Employers Health and Welfare Fund and J.B. Hunt Transport Services, Inc. v. GlaxoSmithKline LLC, an appeal in the Third Circuit Court of Appeals. Our amicus brief addresses overbroad sealing of drug company documents, improperly keeping them from public view despite an important public health and safety interest.
Amicus Brief in Nicopure Labs, LLC v. Food & Drug Administration
Attorneys from CRIT and the Yale Law School Abrams Institute for Freedom of Expression filed an amicus brief on behalf of Yale Law School Professors Robert C. Post, Jack Balkin, and Amy Kapcynski, in Nicopure Labs, LLC v. Food and Drug Administration, an appeal in the D.C. Circuit Court. The case addressed the ability of the FDA to regulate advertising regarding modified-risk tobacco products, such as e-cigarettes and vaporizers.
Collaboration on Amicus Brief in Federal Trade Commission, et al. v. Quincy Bioscience Holding Co., et al.
CRIT joined a consortium of public health groups as amici in an amicus brief filed by Public Citizen, Inc. in Federal Trade Commission, et al. v. Quincy Bioscience Holding Co., et al., a case in the U.S. Court of Appeals for the Second Circuit, a case alleging false or misleading statements in product labeling and advertisements for a dietary supplement marketed for improved memory.
Collaboration on Amicus Brief in Public Citizen, Inc., Natural Resources Defense Council, And Communications Workers of America, AFL-CIO v. Donald J. Trump, et al.
CRIT joined a consortium of public health groups as amici in an amicus brief filed by Gupta Wessler PLLC in Public Citizen, Inc., Natural Resources Defense Council, And Communications Workers of America, AFL-CIO v. DONALD J. TRUMP, et al., a case in the D.C. Circuit Court challenging Executive Order No. 13771, commonly known as the “two-for-one” order.
Amicus Brief in Expressions Hair Salon v. Schneiderman
CRIT, in collaboration with the Media Freedom & Information Access Clinic (MFIA), submitted an amicus brief in December 2016 to the United States Supreme Court in a case dealing with ability of government agencies to regulate the words used by merchants in conveying prices. Our brief informed the court of the ways that a broad ruling could negatively impact the FDA's ability to regulate medical product advertising and marketing. The court's eventual decision was narrow.
Technical Assistance in Settlement Provisions
CRIT researchers and staff, in collaboration with the Media Freedom & Information Access Clinic, provide technical assistance to attorneys regarding model settlement clauses in litigation, designed to increase data sharing regarding medical products.
Challenging Court Secrecy
Litigation can unearth critical information about the safety and effectiveness of drugs and devices in three ways: (1) by exposing improper research and marketing practices that compromise scientific evidence and mislead patients, clinicians, and regulators; (2) by making relevant clinical study data available for independent researchers to investigate; and (3) by informing the public of dangerous medical products and bad corporate conduct, so that they can make informed decisions about their health as consumers. Despite the public health value of disclosure and access, large quantities of information revealed during litigation are kept from the public due to overbroad and unwarranted court secrecy.
In September 2018, CRIT hosted a conference on court secrecy in medical product litigation. We welcomed to New Haven a group of academics and leading litigators, including plaintiffs’ attorneys, public interest attorneys, and consumer protection attorneys, to engage in a series of facilitated discussions about the scope and impact of confidentiality in medical product cases. The goals for the meeting were to better understand the problem of court secrecy, to learn from success stories where important information was disseminated, and to identify feasible solutions for promoting greater public access to information. The meeting report [insert link] contains recommendations for best practices and key principles for proponents of open court records.
Joseph F. Anderson Jr., Secrecy in the Courts: At the Tipping Point, 53 Vill. L. Rev. 811 (2008). http://digitalcommons.law.villanova.edu/vlr/vol53/iss5/2
Benham, Dustin B., Dirty Secrets: The First Amendment in Protective-Order Litigation 35 Cardozo Law Review 1781 (2014). https://papers.ssrn.com/sol3/Data_Integrity_Notice.cfm?abid=2348168
Malone, Patrick and Bauer, Jon, When Secret Settlements are Unethical (May 22, 2015). https://papers.ssrn.com/sol3/papers.cfm?abstract_id=1631844
Resnik, Judith, Uncovering, Disclosing, and Discovering How the Public Dimensions of Court- Based Processes Are at Risk (2006). Faculty Scholarship Series. Paper 696. http://digitalcommons.law.yale.edu/fss_papers/696
David S. Sanson, The Pervasive Problem of Court-Sanctioned Secrecy and the Exigency of National Reform, 53 Duke L.J. 807 (2003). https://scholarship.law.duke.edu/cgi/viewcontent.cgi?article=1210&contex...
Wiggins, Elizabeth C., Pecherski, Melissa J. and Cort, George, Protective Order Activity in Three Federal Judicial Districts, Report to the Advisory Committee on Civil Rules, Federal Judicial Center, April 1996 (1996). https://www.fjc.gov/sites/default/files/2015/0029_0.pdf
Case Law and Guides
Committee on Rules of Practice and Procedure (prepared by Andrea Kuperman), Case Law on Entering Protective Orders, Entering Sealing Orders, and Modifying Protective Orders (July 2010). https://www.uscourts.gov/sites/default/files/caselaw_study_of_discovery_...
Pound Civil Justice Institute, Judicial Transparency and the Rule of Law (2016). http://poundinstitute.org/sites/default/files/Pound-Judges-Forum-Report-...
Bailey, Leslie A. Fighting Protective and Secrecy Orders, AAJ 2013 Annual Convention (2013). https://www.americanbar.org/content/dam/aba/events/professional_responsi...
Bailey, Leslie A. Confronting Court Secrecy Issues from Discovery Through Settlement: Measures to Protect Both Your Client and the Public Interest, 2014 Consumer Rights Litigation Conference (2014). https://www.americanbar.org/content/dam/aba/events/professional_responsi...
Reagan, Robert Timothy, Sealing Court Records and Proceedings: A Pocket Guide, Federal Judicial Center (2010) https://www.fjc.gov/sites/default/files/2012/Sealing_Guide.pdf
Reagan, Robert Timothy, Confidential Discovery: A Pocket Guide on Protective Orders, Federal Judicial Center (2012). https://www.fjc.gov/content/confidential-discovery-pocket-guide-protecti...
The Sedona Conference Working Group on Protective Orders, Confidentiality & Public Access (WG2). The Sedona Guidelines: Best Practices Addressing Protective Orders, Confidentiality & Public Access in Civil Cases. (2007). https://thesedonaconference.org/publication/Working_Group_2_Guidelines
Opposing Views of the Undersigned Members of the Sedona Conference Working Group on Protective Orders, Confidentiality & Public Access (WG2) to the Sedona Guidelines on Protective Orders, Confidentiality & Public Access in Civil Cases, April 6, 2007 (2007). https://thesedonaconference.org/publication/Working_Group_2_Guidelines
David A. Schulz, A Personal Response to the Opposing Views (2007). https://thesedonaconference.org/publication/Working_Group_2_Guidelines
Withers, Kenneth J. (Ed.) Selected Decisions Involving Protective Orders, Confidentiality & Public Access, The Sedona Conference (May 1, 2011) http://citpsite.s3.amazonaws.com/events/privacy-access/2011-05-Privacy_A...