" Strengthening the FDA’s Enforcement of ClinicalTrials.gov Reporting Requirements ," 326 Journal of the American Medical Association 2131 (2021) (with Reshma Ramachandran and Joseph S. Ross)

"Strengthening the FDA’s Enforcement of ClinicalTrials.gov Reporting Requirements," 326 *Journal of the American Medical Association* 2131 (2021) (with Reshma Ramachandran and Joseph S. Ross)

Reshma Ramachandran et al., Strengthening the FDA’s Enforcement of ClinicalTrials.gov Reporting Requirements, 326 JAMA 2131 (2021)

Reshma Ramachandran
Christopher J. Morten
Joseph S. Ross

However, reporting of results information remains limited despite the legal mandate and clear instructions from DHHS and the NIH Final Rule. Recent estimates suggest that approximately 60% of trials fail to report results on time and more than 30% (almost 3000 clinical trials with primary completion dates between January 18, 2017, and January 18, 2021) have not yet reported results. 3 Among 3951 trials sponsored by industry, 43.2% complied fully with the FDAAA results reporting requirements. 3 Among the top 40 US research universities (by number of trials subject to the FDAAA), only 17 complied fully with reporting of trial results. 4 The FDA and NIH share responsibility for enforcing FDAAA. The NIH has independent authority and obligations under the FDAAA to withhold grant money from grantees who do not comply with their FDAAA reporting requirements, yet the NIH has historically declined to take any enforcement action on its own. 5 However, when the FDA issued its Notice of Noncom-pliancetoAcceleron,theNIHupdatedtheClinicalTrials.gov entry for the Acceleron trial with a public notice of "FDAAA 801 Violation." 6 This constituted, to our knowledge, the NIH's first public acknowledgment of a specific trial out of compliance with the FDAAA. Further Notices of Noncompliance from the FDA may trigger, or even require, the NIH to take separate enforcement actions, including withholding grant money from noncompliant grantees. For its part, the FDA has stated that it identifies potential violations of the FDAAA through investigations conducted as part of the agency's BIMO (Bioresearch Monitoring) program as well as third-party complaints. 7 The FDA then takes a "risk-based approach" "consistent with FDA's public health mission" and, at its discretion, may issue a Preliminary Notice of Noncompliance (hereafter referred to as Pre-Notice) informing responsible parties of potential FDAAA violations. 7 Pre-Notices alert responsible parties that the agency plans to check on the potential missing trial results information (including study protocol and statistical analysis plan) 30 days after receipt of the Pre-Notice. Only after Pre-Notices are sent will the FDA issue a Notice of Noncompliance if results information remains missing. Pre-Notices also warn responsible parties that if the required information is not submitted, the FDA may take enforcement action, potentially levying civil monetary penalties of more than $10 000 for each day of violation or opening criminal prosecution should the party continue to fail to submit required information. Through an ongoing Freedom of Information Actbased investigation, all 58 Pre-Notices that the FDA issued from2013throughApril29,2021,wereobtained.Ofthese, 57 described potential missing trial results information and 1 described missing registration information. Three trends stand out. First, the 57 Pre-Notices represent a tiny fraction of the thou-sandsofFDAAA-applicableclinicaltrialsidentifiedasnoncompliantwith results information reporting requirements as of January 2021. 3 Second, the FDA sent no Pre-Notices to any federal agencies, including the NIH, even though the NIH is the responsible party for many trials that havenotsubmittedmandatedresultstoClinicalTrials.gov.Instead,most Pre-Notices were sent to industry, with a smaller number sent to academia and other organizations (Supplement). Third, Pre-Notices may be effective at improving compliance: as of August 17, 2021, more than 90% of the 57 Pre-Notice recipients had reported missing information to ClinicalTrials.gov. Among recipients who submitted missing results information after receiving a Pre-Notice, the median time for submission was approximately 3 weeks. The FDA has since taken additional action to enforce FDAAA compliance. In July and August 2021, it issued 2 additional Notices of Noncompliance 1 -onetoAccuitisforaphase2trialofatopicaltreatment for acne rosacea 8 and another to an academic investigator for a phase 4 trial of a postoperative combination ice and analgesic treatment. 9 But the FDA's enforcement efforts could be strengthened substantially. First, the FDA could send more Pre-Notices. The FDA has yet to send Pre-Notices (or Notices) to thousands of responsible parties that have not reported results, including government sponsors such as the NIH. Moreover, in lieu of relying on inconsistent BIMO investigations and third-party complaints to identify noncompliant trials, the FDA could instead use a continually updated list of FDAAA 801 problems 10 maintained by the NIH to quickly identify potential noncompliant trials and issue Pre-Notices as appropriate. Second, the FDA could publicize all Pre-Notices it issues, as opposed to sharing them only with responsible parties. As with Notices of Noncompliance, Pre-Notices could be posted on the FDA website and cross-linked on ClinicalTrials.gov. Such transparency would improve public accountability and encourage prompt submission of missing information. Third, the FDA could ensure that Pre-Notices present clear timelinesforfurtherenforcementactionsifresultsremainunreported.Within Pre-Notices, the FDA does not currently state specifically when subse-quentenforcementactionswilloccuriftheFDAdeterminestheresponsible party is noncompliant, including when a Notice of Noncompliance willbeissued.Additionally,whentheFDAdeterminesaresponsibleparty is noncompliant, the FDA could immediately send a Notice of Noncompliance that establishes a clear timeline for escalating consequences of continued noncompliance, including civil monetary penalties. Notices may succeed even where Pre-Notices fail: within a month of receiving their Notices of Noncompliance, all 3 sponsors reported their missing results information to ClinicalTrials.gov. 6,8,9 Fourth, if FDA resources or personnel remain constrained, the agency could set and consistently apply objective criteria for prioritization of enforcement efforts. These might be based on the "riskbased" approach outlined in the FDA's issued guidance 7 and include duration of noncompliance, trial size, patient population affected, severity of disease, and availability of alternative treatments. The NIH could support the FDA and improve its own enforcement efforts. Rather than wait for the FDA to send Pre-Notices and Notices, the NIH could use its own list of FDAAA 801 problems 10 to identify noncompliant trials and send reminders to the responsible parties. If a responsible party is an NIH grantee, the NIH could also warn that future grant funds may be withheld until the trial comes into compliance. Additionally, Congress could act by explicitly allocating funding for FDAAA enforcement efforts by the NIH and FDA, because the FDAAA imposed new regulatory obligations on both without allocating new funds. The FDA can and should harness its enforcement tools to ensure timely submission of trial results information to ClinicalTrials.gov. By doing so, the FDA could bring important missing results to light and demonstrate its commitment to protecting patients through clinical trial transparency. JAMA December 7, 2021 Volume 326, Number 21 (Reprinted) jama.com © 2021 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ Northeastern University Libraries by Christopher Morten on 06/02/2022


Stripping the Courts’ Jurisdiction

" Stripping the Courts’ Jurisdiction ," American Prospect , May 5, 2021

"Stripping the Courts’ Jurisdiction," *American Prospect*, May 5, 2021

Christopher Jon Sprigman, Stripping the Courts’ Jurisdiction, American Prospect (May 5, 2021), https://prospect.org/justice/stripping-the-courts-jurisdiction/

Last week, we learned that Justice Amy Coney Barrett, whom the GOP put on the Supreme Court in the dying days of Trump’s presidency, will be paid a $2 million advance for a book about how judges are not supposed to bring their personal feelings into how they rule. Set aside for a moment the unseemliness of Barrett so rapidly cashing in on her new position. More important is the signal Barrett’s book deal sends about the Supreme Court. If it weren’t for the Court’s extraordinary power—to create rights, and, as Roe v. Wade and the right to legal abortion hang in the balance, to take them away—no publisher would pay that kind of money for a novice judge’s opinions. All of which should lead us to ask why nine unelected judges are given the power to make so many important decisions in the first place. Most Americans perceive the Court as an integral part of our democracy. But in reality, the relationship of judges to democracy is more complicated, and at times, antagonistic. By enforcing constitutional rules, judicial review helps to smooth out democracy’s rough edges. But when they overturn democratically enacted laws, judges also shrink our capacity to make decisions for ourselves. And if judges overdo it, judicial review can preempt necessary democratic development. At the extreme, instead of making democratic life more decent and predictable, interventionist courts can spark long-lasting and intense conflict. When they overturn democratically enacted laws, judges shrink our capacity to make decisions for ourselves. When they overturn democratically enacted laws, judges shrink our capacity to make decisions for ourselves. That’s what happened in 1857 when the Supreme Court stepped in to stop Congress from prohibiting slavery in U.S. territories. It hoped its decision in the Dred Scott case would lead the nation away from conflict. But if anything, Dred Scott hastened our descent into civil war. That’s also what happened in 1973 when the Supreme Court stepped in to preempt the democratic debate and declare abortion a right in Roe v. Wade. The backlash from that decision became a defining feature of American politics. The English language itself became a field of battle, with “pro-life” and “pro-choice” sides unable to agree even on nomenclature. But the deepest threat that judicial review poses for democracy lies ahead of us. Republicans have built their recent political strategy around stocking the federal bench with right-wing partisans. And they’ve done so for a reason: Demographic change is making it increasingly difficult for the GOP to win elections, but a conservative judiciary can stand in the way of much of what Democrats and a majority of Americans hope to accomplish. The conservative Supreme Court would likely intervene, for example, to limit attempts to address global warming, to expand health care, to enforce rational public-health laws, or to tax the very wealthy. In all these cases, the Supreme Court would not be enforcing any clear text in the Constitution. It would be exercising raw power. For any committed small-d democrat, this sort of politicized judging is unacceptable. And opposition is starting to build: We’ve seen a slew of recent court reform proposals, including judicial term limits, Supreme Court supermajority voting requirements, and, perhaps most prominently, court-packing. In the end, though, none of these get to the heart of the problem, which isn’t that judges are too liberal or too conservative. It’s that judges are simply too powerful. We need a deeper reform, one that the Constitution specifically authorizes. Article III of the Constitution gives Congress the power to strip federal courts’ jurisdiction: a power that can be employed to rein in politicized courts and even to override judges when they stand in the way of change that a substantial and enduring political majority wants. How would jurisdiction-stripping work? Article III, Section 1 gives Congress complete discretion on whether to create the lower federal courts, a power that Congress has used from the founding to limit lower courts’ jurisdiction. And Article III, Section 2, Clause 2 explicitly empowers Congress to make “exceptions” to the Supreme Court’s appellate jurisdiction—that is, to pick and choose within approximately 99 percent of the Supreme Court’s total docket what cases the Court has the power to hear. So, imagine Congress passes the John Lewis Voting Rights Act, which would put an end to a looming wave of GOP-sponsored voter suppression laws. Given the Supreme Court’s hostility to voting rights (demonstrated in cases like 2013’s Shelby County v. Holder, where a 5-4 majority of the Court struck down provisions of the 1965 Voting Rights Act), Congress would be well-advised to include in its new legislation language stripping the federal courts’ authority to review it. In so doing, Congress would be advancing its own understanding of its power to guarantee the voting rights of all Americans—and telling courts to stay out. If voters disagree, either with the federal government’s interference in states’ decisions about election rules, or with Congress’s decision to limit judicial review, they can discipline Congress in the next election. Crucially, Congress’s power to rein in the courts through jurisdiction-stripping isn’t partisan: It can be used by Republicans as well as by Democrats. In the end, the jurisdiction-stripping strategy isn’t about which side wins in any particular political struggle—although The Wall Street Journal editorial page, characteristically, has given the basest partisan spin to the idea by recommending that Republicans use it as revenge if Democrats pack the Supreme Court. The legitimate use of jurisdiction-stripping, by contrast, would be a way to strike a better balance between judicial review and democracy. Which would return us to a saner world where Amy Coney Barrett doesn’t wield the kind of unreviewable judicial power that gets her a $2 million book deal.


" Systematic Overview of Freedom of Information Act Requests to the Department of Health and Human Services from 2008 to 2017 ," 4 Research Integrity and Peer Review , Article number 26, 2019, at 1 (with Alexander C. Egilman, Joshua D. Wallach, Peter Lurie and Joseph S. Ross)

"Systematic Overview of Freedom of Information Act Requests to the Department of Health and Human Services from 2008 to 2017," 4 *Research Integrity and Peer Review*, Article number 26, 2019, at 1 (with Alexander C. Egilman, Joshua D. Wallach, Peter Lurie and Joseph S. Ross)

Alexander C. Egilman et al., Systematic Overview of Freedom of Information Act Requests to the Department of Health and Human Services from 2008 to 2017, 4 Rsch. Integrity & Peer Rev., Art. 26, 2019, at 1

Alexander C. Egilman
Christopher J. Morten
Joseph S. Ross

The Freedom of Information Act (FOIA) can enhance transparency and accountability of biomedical research and regulatory agencies by providing access to a wide range of records held by government agencies. The Act requires federal agencies to disclose unreleased records upon request by the public, unless records fall under nine specific exemptions protecting interests such as trade secrets and other confidential commercial information, personal privacy, and national security [1]. At the Department of Health and Human Services (HHS), which has many constituent agencies, such as the Centers for Medicare and Medicaid Services (CMS), the Food and Drug Administration (FDA), the National Institutes of Health (NIH), and the Centers for Disease Control and Prevention (CDC), records subject to FOIA that might be helpful for advancing public health include aggregated billing records, medical product safety and efficacy data, abandoned New Drug Applications, and information related to research integrity [2][3][4]. Several recent examples demonstrate the beneficial role FOIA can play. Emails obtained by the New York Times through FOIA revealed that alcohol manufacturers had funded and shaped a major study at the National Institute on Alcohol Abuse and Alcoholism (NIAAA) examining the effects of moderate alcohol consumption on cardiovascular disease [3]. In the wake of the Times article, the NIH launched an internal review that found that interactions between NIAAA officials and alcohol industry biased the design of the study to demonstrate a beneficial health effect of moderate alcohol consumption, ultimately leading the NIH to terminate the study and to undertake a wider audit of industry influence on its research activities [5]. In another example, a review of emails obtained under FOIA revealed that the Coca-Cola Company gained access to and influence with employees at the CDC and advanced corporate objectives, such as by downplaying the association between sugar-sweetened beverages and obesity [6]. In these and other examples, information accessed under FOIA has helped uncover undue influence on clinical research as well as on public health practitioners. FOIA can also be used to provide access to clinical trial data. For example, the Treatment Action Group and the Global Health Justice Partnership used FOIA to obtain clinical trial data including clinical study reports, study protocols, and individual patient-level data, albeit heavily redacted, on the Hepatitis C drugs Sovaldi and Harvoni, enabling the research community to independently assess the safety and efficacy of the drugs [7]. In many cases, FOIA may be the only mechanism for the public to gain access to certain types of trial data of medical products approved by the FDA. Despite several examples in which FOIA requests have helped inform the clinical and scientific communities, little empirical data exists on FOIA requests to HHS. A previous evaluation of FOIA requests to the FDA focused on classifying requesters and found that of the over 10,000 requests in 2013, 75% were filed by commercial requesters, 12% by news media, and 13% by all other requesters [8]. In addition to the commercialization of FOIA, individuals and news media have raised concerns related to timely processing, improper denials, and costs associated with processing and litigating FOIA requests [9,10]. Therefore, we characterized FOIA requests to HHS agencies, including request outcomes, processing times, backlogs, and costs, providing a systematic overview of all FOIA requests to HHS from 2008 through 2017. Using HHS's FOIA annual reports [11], we determined the number of FOIA requests received and processed by HHS agencies between 2008 and 2017. We selected that 10-year span because it comprised the most recent years of publicly available HHS FOIA annual reports at the time of the analysis. We extracted data on request outcomes, based on the agencies' own categorization: fully granted, partially granted/partially denied, fully denied based on any of the nine FOIA exemptions, and fully denied for other reasons. Based on the distribution of the data, requests were stratified by those to CMS, FDA, and all other HHS divisions (Additional file 1: Table S1). Agencies are required by statute to respond to FOIA requests within 20 days for any request comporting with agency regulations, unless there are "unusual circumstances, " such as a need to review a voluminous number of records [12]. Requests are assigned to one of two tracks, simple or complex, based on estimated processing needed. The criteria, such as the estimated search and redaction time, used to assign requests to the simple or complex track may vary across agencies. The FOIA annual reports include the number of simple and complex requests processed within 20and 100-day increments across categories ranging from < 1 to 200 days and 200 to 400 days, respectively. We report processing times in three time increments: < 1-20, 21-60, and 61+ days, based on the 20-day statutory response requirement and because when FOIA requests are litigated and plaintiffs prevail, courts commonly order document production within 60 days [13,14]. We also collected information about the backlog (requests pending beyond the 20business-day statutory response period.) Costs, including both processing and litigation costs, as well as fees collected for search time, document review, and duplication were also calculated. All calculations were performed using Microsoft Excel (v.15.28). Between 2008 and 2017, 69.6% of 530,094 HHS FOIA requests were received by CMS, 18.9% by FDA, and 11.6% by other HHS agencies (Table 1). In this 10-year period, CMS processed 374,728 requests, FDA 114,938, and other HHS agencies 61,890, including some requests submitted before 2008. Over the study period, requests processed by CMS decreased 56.0% while remaining stable for FDA since 2010. CMS fully or partially granted 60.3% of requests whereas FDA fully or partially granted 72.4%. The percentage of requests fully or partially granted by CMS decreased by 43.1% while increasing by 20.9% for FDA. CMS and FDA fully denied 99,616 (26.6%) and 30,254 (26.3%) of requests based on reasons other than exemptions, respectively, while denying 49,263 (13.1%) and 1420 (1.2%) based on exemptions, respectively. No records or withdrawn requests were the most common reasons for full denials (Table 2). CMS most commonly invoked FOIA exemption 6 (personal privacy; 86.1% of its denials related to exemptions) to withhold requested information, while FDA most commonly invoked exemption 4 (trade secrets and other confidential commercial information; 36.1% of its denials related to exemptions) (Table 3). Between 2008 and 2017, 82.0% of requests to CMS were considered simple and 18.0% complex; 82.2% of simple requests and 54.9% of complex requests were Inter-agency or intra-agency communications that are protected by legal privileges f Exemption 6: Information that, if disclosed, would invade another individual's personal privacy g Exemption 7: Information compiled for law enforcement purposes that: 7(A). Could reasonably be expected to interfere with enforcement proceedings 7(B). Would deprive a person of a right to a fair trial or an impartial adjudication 7(C). Could reasonably be expected to constitute an unwarranted invasion of personal privacy 7(D). Could reasonably be expected to disclose the identity of a confidential source 7(E). Would disclose techniques and procedures for law enforcement investigations or prosecutions, or would disclose guidelines for law enforcement investigations or prosecutions if such disclosure could reasonably be expected to risk circumvention of the law 7(F). Could reasonably be expected to endanger the life or physical safety of any individual h Exemption 8: Information that concerns the supervision of financial institutions i Exemption 9: Geological information on wells approximately 63,500 exemptions the agency asserted to withhold requested information. However, FDA most commonly invoked exemption 4 (trade secrets and other confidential commercial information). Previously, researchers have suggested that FDA at times invoked exemption 4 even when withholding under that exemption is not warranted under the relevant legal standard [4,15]. CMS and other HHS agencies processed more than three-fourths and one-half of requests within 20 days, respectively, whereas two-thirds of requests processed by FDA took more than 61 days. Requests to FDA were generally more complex than those to CMS, which likely contributed to FDA's slower processing time. In addition, FDA addressed potentially complex issues related to FOIA exemption 4 (trade secrets and other confidential commercial information) at a higher rate than CMS, and fully denied requests less frequently, which may have also contributed to FDA's slower processing speed. However, even within the simple request category, FDA required more than 61 days to process over one-half of requests, compared to 5.6% at CMS and 14.5% at other HHS agencies, suggesting there may be opportunity for FDA to increase its processing speed to more closely align with other HHS agencies. To Fig. 1 Processing time for perfected Freedom of Information Act requests processed by Department of Health and Human Services Agencies, 2008-2017 (perfected Freedom of Information Act requests are requests for records which reasonably describe such records and are made in accordance with published rules stating the time, place, fees (if any) and procedures to be followed) reduce delays, HHS agencies should consider hiring more personnel and devoting greater resources to responding to FOIA requests. The number of backlogged requests across HHS agencies was reduced by 76.5% over the 10-year span, suggesting that efforts implemented in response to an Obama administration instruction in 2009 to reduce federal agency FOIA backlogs have been effective [16]. The FOIA director at HHS, Michael Marquis, has noted that improved communication with requesters and greater staff accountability were particularly instrumental in meeting the backlog reduction goals [16]. We found that between 2008 and 2017 costs to HHS associated with FOIA requests totaled over $400 million, with requests to FDA comprising nearly 70% of overall HHS costs. The large number of complex requests FDA receives is likely a contributing factor to its disproportionate costs. Costs to HHS per FOIA request more than tripled during the 10-year span. Growth in the number of employees responsible for handling FOIA requests may have contributed to the increase in processing costs. Despite rapidly growing costs, HHS recovered just 1.9% of total costs. A possible explanation for the minimal fees HHS collected is that its agencies are simply not following FOIA fee guidelines, which require commercial use requesters to be charged for any search time, document review, and duplication; news media, educational, or scientific requesters to be charged for duplication only; and all other requesters to be charged for search time and duplication [17]. Another possibility is that fee rates are very low relative to costs. Agencies might consider increasing FOIA fees for commercial use requesters in order to recover more of the agency's costs. Simultaneously, HHS should strive to make FOIA more affordable and accessible for those requesting information in the public interest, particularly given our finding that nearly 7000 requests to HHS agencies were fully denied for failure or inability to pay the associated fee. Given growing costs, minimal fees collected, and sometimes lengthy process times, HHS agencies, and particularly the FDA, should consider expanding efforts to proactively disclose records. These efforts might both improve agency transparency and make FOIA programs more efficient. For example, FDA advisory committee materials used to be confidential until they were the subject of FOIA requests, but the FDA changed its practice to proactively release such materials, which has provided useful information for the public and saved the agency time responding to FOIA requests. Notable types of records that HHS agencies might consider proactively disclosing include for the FDA; clinical study reports, final reports of clinical trials that fulfill postmarketing requirements and commitments, and Risk Evaluation and Mitigation Strategies; for CMS, provider level claims and spending data; and for NIH and CDC, expenditures on preclinical and clinical research and development, agency-held intellectual property, and payments to and from industry [18,19]. This study was limited to aggregate information on FOIA requests to HHS, which did not include information on the types of entities, such as news media, academics, or commercial requesters, who requested records, the information requested and released, and the appropriateness of agencies' withholding of information. Further, we could not determine whether multiple FOIA requests were for the same materials nor the redundancy in the materials requested, which has implications for HHS's costs of processing requests. Between 2008 and 2017, over 500,000 FOIA requests were made to HHS agencies, nearly 90% of which were to CMS or FDA, demonstrating that FOIA is an important tool for obtaining information about HHS and its agencies. While nearly two-thirds of requests were fully granted and processed within 20 days, onequarter required 61 days or longer. Requests to FDA were generally more complex, took longer to process, and were costlier to process than those to CMS. Given growing costs, minimal fees collected, and lengthy process times, HHS agency FOIA programs might be made more efficient through greater proactive record disclosure. Costs responding to Freedom of Information Act requests by Department of Health and Human Services Agencies, 2008-2017 Egilman et al. Research Integrity and Peer Review (2019) 4:26 * 18991 (14.5%) * 19588 (14.5%) * 20182 (23.1%) * 21436 (31.0%) * 99966 (18.9%) * FOIA requests processed, No. 32435 (27.7%) * 20481 (14.6%) * 20194 (14.8%) * 20336 (23.2%) * 21492 (30.4%) * 114938 (20.8%) * a Other HHS agencies in the analysis include the following: Administration on Aging, Administration for Children and Families, Administration for Community Living, Agency for Healthcare Research and Quality, Centers for Disease Control and Prevention, Health Resources and Services Administration, Indian Health Service, National Institutes of Health, Office of the Assistant Secretary for Health, Office of Inspector General, Office of Public Health and Science, Office of the Secretary, and Substance Abuse and Mental Health Services Administration b The number of FOIA requests processed exceeds the number of FOIA requests received because some FOIA requests received prior to 2008 were processed in 2008 or afterwards *Percentages of the HHS totals; all other percentages are of respective HHS agency totals † Some backlogged requests may be counted twice within each 2-year increment a Exemption 1: Classified national defense and foreign relations information