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Public Comment Regarding Accelerated Approval and Considerations for Determining Whether a Confirmatory Trial is Underway

Policy, Testimony & Briefings

March 10, 2025 — (Docket No. FDA-2024-D-3334)

The National Center for Health Research (NCHR) [and the Cancer Prevention and Treatment Fund] appreciate[s] the opportunity to comment on the FDA’s draft guidance on Accelerated Approval and Considerations for Determining Whether a Confirmatory Trial is Underway. We strongly support the FDA’s efforts to ensure timely completion of confirmatory trials; however, we have concerns regarding the vagueness of key criteria to be used to determine when a trial is considered “underway.” FDA’s clearly defined and specified regulatory expectations are needed to improve corporate achievements and public trust in the Accelerated Approval process.

Concerns About Imprecise Language & Lack of Specificity

As currently written, the guidance relies heavily on important terms such as “diligent and timely,” which are very vague and leave room for inconsistent interpretation by sponsors. Unfortunately, some companies’ definitions of diligent and timely will not be considered timely or diligent by regulators or public health experts and will not reduce the frequent delays in the completion of confirmatory trials. The lack of specific enrollment and timeline benchmarks will result in delays that expose patients to drugs without verified clinical benefit for many years.This is exactly the situation that the guidance is intended to correct. For that reason, we strongly recommend that the FDA replace ambiguous terms with clear, measurable criteria, including concrete benchmarks and milestones and clearly defined interim analyses to avoid delays.

Timeline for confirmatory trials. The draft guidance states that a confirmatory trial’s target completion date should be “consistent with diligent and timely conduct.” This language is too broad and subjective, resulting in a wide range of timelines for target completion dates, many of which will be lengthier than necessary. Since these are just the target completion dates, the actual completion dates are likely to be even later, and there are no specific warnings or penalties in the guidance of how the FDA plans to strengthen accountability. Instead of this vague wording, the FDA should specify that confirmatory trials should be completed within 1-3 years of accelerated approval, depending on how rare the disease is and how large and longitudinal the study is.That is consistent with a review of oncology drugs granted accelerated approval from December 11, 1992, to May 31, 2017.[1] Although 40% of the 93 indications had not yet completed confirmatory trials or verified benefit when the study was published in 2018,  those with confirmatory trials underway at the time of approval were verified after a median of 3.1 years. For the 9 indications without ongoing trials at the time of approval, those that were verified later were verified after a median of 5.5 years, ranging from 0.5 to 12.6 years. Additionally, 8 indications had remained on the market for more than 5 years without verifying their benefit, and 5 indications (5%) were withdrawn from the market. These findings confirm that a substantial percentage of confirmatory studies experience delays or remain incomplete for extended periods, highlighting the need for stronger regulatory oversight to ensure timely completion and protect patient safety.

Patient Enrollment Prior to Approval. The current guidance states that “enrollment of the confirmatory trial has been initiated.” This needs to be clarified. Does “enrollment has been initiated” mean that:

  • one or more patients were enrolled
  • or some number or percentage of patients have been identified as suitable but have not yet agreed to participate
  • or some number or percentage have started providing baseline data
  • or some number or percentage of patients have started treatment
  • or some number or percentage of patients have almost completed treatment?

A 2015 study found that 19% of clinical trials failed to meet accrual goals or were terminated early due to insufficient enrollment, with recruitment challenges cited as a major barrier to trial completion.[2] That is why it is essential that “enrollment has been initiated” be defined as a substantial number of patients (such as 25 patients or 25% of patients, whichever is larger) already have been in treatment long enough to determine if adverse events or other missing data are likely to be a problem.That would better ensure that the trial is feasible as designed.

We agree with the guidance that completion of a confirmatory trial will be compromised when a drug granted accelerated approval becomes available on the market. This is especially a concern when the trial is a randomized, blinded trial, but it is also important to ensure an appropriate comparison sample for any confirmatory study. For that reason, it is essential that all patients be enrolled for most of the planned length of the trial prior to granting accelerated approval or at least prior to making the newly approved drug available on the market. FDA should not permit researchers to break the blinding of an ongoing study or switch to open label as soon as a product has been approved, because it undermines the integrity of the study and makes any results inconclusive or potentially inaccurate. That is unfair to all the patients who enrolled in the study, whether in the experimental or control group, because the study becomes useless in terms of determining the safety and efficacy of the treatment compared to a control group.

We agree with the guidance that “to ensure the confirmatory trial enrolls and retains sufficient U.S. participants, the sponsor’s enrollment strategy should prioritize early U.S. recruitment.” Because of demographic differences, differences in health habits, and differences in medical care and medical systems, U.S. study participants should be considered the most important study population for confirmatory trials submitted to the FDA. However, we disagree with the guidance that implies it is sufficient for the U.S. recruitment “be closer to completion at the time of accelerated approval.” Instead, recruitment in the U.S. should be completed and the treatment of those U.S. study participants should be near completion.

Progress Reports. The 180-day progress reports need to be improved by requiring them to include recruitment rates, patient retention, adverse events and other safety concerns, and additional metrics that will help identify barriers to the timely completion of the study. FDA guidance should clarify what is acceptable and not acceptable if enrollment targets are not met or drop out rates or missing data undermine the integrity of the study.These reporting requirements will improve transparency and accountability and help ensure a level playing field among companies conducting confirmatory trials.

Concerns Regarding Rare Disease Trials. The FDA acknowledges the unique challenges of conducting randomized post-marketing confirmatory trials for certain rare diseases, particularly those with very small populations and high unmet need. As a result, the proposed guidance permits non-randomized post-marketing studies and, in some cases, does not require that a confirmatory trial be underway before granting accelerated approval—provided there is appropriate justification.

While we recognize the difficulties in patient recruitment and trial feasibility in rare disease settings, this plan is overly flexible and will inevitably result in patients, CMS,  and other healthcare entities spending millions of dollars on treatments that have not been proven to provide meaningful clinical benefits. An example of this is the case with Sarepta accelerated approval drugs for Duchenne Muscular Dystrophy.[3] Without a clear requirement that studies be underway, patients will not have the information they need to make informed treatment decisions for many years, and meanwhile other companies will have less incentive to develop new treatments and conduct their studies in a timely manner. Furthermore, the FDA guidance allowing confirmatory trials to be a continuation of the accelerated approval’s trial evaluating the same surrogate endpoint should not be considered to be a confirmatory trial, since many surrogates do not accurately predict a clinically meaningful outcome. However, continuing the initial study for a confirmatory trial that follows the study participants for a longer period of time to evaluate a meaningful clinical endpoint should be encouraged. We previously raised our objection to confirmatory trials that use unproven biomarkers and surrogate endpoints that are not clinically meaningful in our comment for the guidance entitled “Expedited Program for Serious Conditions—Accelerated Approval of Drugs and Biologics” [Docket No. FDA-2024-D-2033], which highlighted the need for stronger evidence.[4]

Patients with rare diseases are desperate for treatments, but deserve better efficacy evidence than has often been provided by the many expensive treatments approved by the FDA. Patients will not get the evidence they need unless the FDA requires specific enrollment milestones pre-approval and a clearly defined timeline for confirmatory trials, with FDA providing incentives to comply and penalties or disincentives for non-compliance. If studies take longer than promised, the FDA should require companies to allow patients to have free access to the drugs under the FDA’s expanded access program until the confirmatory trial is completed. This would balance the need for patient access with scientific rigor and patient safety.

Conclusions

We support the FDA’s efforts to improve the accelerated approval process, but the vague wording of this guidance is very unlikely to achieve that goal. The FDA needs to be more specific and less “flexible” to ensure that confirmatory trials are completed within a few years of accelerated approval and that the trials provide the clinically meaningful information that patients need to make informed decisions.

References

[1] Beaver, J. A., Howie, L. J., Pelosof, L., Kim, T., Liu, J., Goldberg, K. B., Sridhara, R., Blumenthal, G. M., Farrell, A. T., Keegan, P., Pazdur, R., & Kluetz, P. G. (2018). A 25-year experience of US Food and Drug Administration accelerated approval of malignant hematology and oncology drugs and biologics: A review. JAMA Oncology, 4(6), 849–856. https://doi.org/10.1001/jamaoncol.2017.5618

[2] Bull, J., Uhlenbrauck, G., Mahon, E., Furlong, P., & Roberts, J. (2015, September 3). Barriers to clinical trial recruitment and possible solutions: A stakeholder survey. Applied Clinical Trials. https://www.appliedclinicaltrialsonline.com/view/barriers-clinical-trial-recruitment-and-possible-solutions-stakeholder-survey

[3] Bendicksen, L., Zuckerman, D. M., Avorn, J., Phillips, S., & Kesselheim, A. S. (2023). The Regulatory Repercussions of Approving Muscular Dystrophy Medications on the Basis of Limited Evidence. Annals of internal medicine, 176(9), 1251–1256. https://doi.org/10.7326/M23-1073

[4] National Center for Health Research. (2025, February 4). Public comment on FDA draft guidance: Expedited program for serious conditions—Accelerated approval of drugs and biologics (Docket No. FDA-2024-D-2033). National Center for Health Research. https://www.center4research.org/nchr-comment-accelerated-approval-draft-guidance

Pfizer hires FDA drug regulator Cavazzoni, sparking revolving door debate

In the News, News Stories & Editorials, We're In the News

David Lim, Politico, February 24, 2025

Pfizer has tapped the FDA’s former top drug regulator, Dr. Patrizia Cavazzoni, as its chief medical officer, the pharmaceutical company announced on Monday.

Allies of the new health secretary, Robert F. Kennedy Jr., seized on the news, pointing to Cavazzoni’s hire as proof of the revolving door with industry that Kennedy has long alleged is corrupting the FDA’s priorities and preventing it from taking a more skeptical view toward vaccines and other drugs.

“This is the core rot in American regulation,” Dr. Vinay Prasad, a professor at the University of California, San Francisco who is in the running for a job in Kennedy’s department, wrote in a blog post. “I find this behavior abhorrent, and it should be criminal. Mr. Kennedy has vowed to stop this, and I welcome that.”

The hire also drew criticism from public health advocacy groups that aren’t aligned with Kennedy.

“Cavazzoni’s move demonstrates that the revolving door between the FDA and the industries it regulates is alive and well,” said Dr. Robert Steinbrook, the director of Public Citizen’s Health Research Group.

Before joining the FDA in January 2018 as the deputy director of operations in the agency’s Center for Drug Evaluation and Research, Cavazzoni worked at Pfizer leading clinical sciences and development operations.

[…]

Cavazzoni will formally start the new role on March 1, according to Pfizer spokesperson Amy Rose. She will report to Dr. Chris Boshoff, Pfizer’s chief scientific officer and president of its research and development arm. Endpoints News and STAT first reported news of Cavazzoni’s new job.

Diana Zuckerman, the president of the National Center for Health Research, a nonprofit, said she’s watching to see who chooses Cavazzoni’s permanent replacement as the nation’s top drug regulator: Trump’s pick to lead the FDA, the as-yet-unconfirmed Johns Hopkins University surgeon Dr. Marty Makary, or Kennedy, a longtime critic of vaccination, or someone else in the administration.

“This is the problem with this revolving door at FDA, people go from industry to FDA and then while they are at FDA they still seem to be strongly aligned with industry and then when they leave FDA they go back to industry,” Zuckerman said. “It raises a lot of questions about how objective they are when they are supposed to be working for the public at the FDA.”

 

Read the article in Politico here: https://subscriber.politicopro.com/article/2025/02/pfizer-hires-fda-drug-regulator-cavazzoni-sparking-revolving-door-debate-00205735?site=pro&prod=alert&prodname=alertmail&linktype=article&source=email.

FDA webpages on clinical trial diversity removed after Trump orders

In the News, News Stories & Editorials, We're In the News

Elise Reuter, MedTech Dive, Jan. 27, 2025

Two days into the Trump administration, several webpages covering diversity in clinical trials, annual medical device reports and LGBTQ+ information were removed from the Food and Drug Administration’s website. It’s not clear if the changes are temporary or if the pages will be restored.

When asked about the removed webpages, an FDA spokesperson directed MedTech Dive to contact the Department of Health and Human Services. The HHS did not respond to multiple requests for comment.

“It is definitely not typical,” said Diana Zuckerman, president of the National Center for Health Research. “From one administration to another, certain things are reviewed and taken down. I don’t think ever [in] the first week of the administration.” 

Other federal websites have scrubbed pages on diversity, equity and inclusion; mentions of the acronym LGBTQ+; federal policies on people with disabilities and abortion search results, according to reporting by Politico, NBC News, the Washington Post and NPR. The Trump administration has also frozen health research grants, according to STAT News.

Some of the removed FDA pages related to efforts around diversity, gender and health equity.

“Surely there’s someone who’s knowledgeable enough about science to understand the importance of diversity in clinical trials,” Zuckerman said of the Trump administration. 

A recent draft guidance from the FDA’s Center for Devices and Radiological Health providing recommendations for medical device sponsors to consider sex- and gender-specific data in clinical studies was removed. The guidance was released on Jan. 6, and the page was last archived to the Internet Archive’s Wayback Machine on Jan. 14. As of Monday, the guidance was available through the Federal Register’s website.

Last week, President Donald Trump issued a raft of executive orders targeting DEI programs. One order called for the removal of federal DEI mandates, policies, programs, preferences and activities “under whatever name they appear.” Trump also issued an order stating that official U.S. policy recognizes two sexes as assigned at birth, male or female. The order contradicts medical groups, including the American Medical Association, that recognize sex and gender identity as a spectrum.

Although guidances are not legally enforceable, “it is troubling that this is happening,” said Michael Abrams, a senior health researcher at consumer advocacy nonprofit Public Citizen.

Most of the information in the guidance was “common sense,” said Madris Kinard, CEO of Device Events, a company that tracks the FDA’s adverse event reports and recalls.  “This is research on making sure you include the right populations that are relevant to the device that you’re approving or clearing,” Kinard added.

Several of the CDRH’s annual reports were also pulled from the center’s site Wednesday afternoon. CDRH released and posted its 2024 report Jan. 17.

Meanwhile, Dorothy Fink, the HHS’ acting secretary, ordered a pause on Jan. 21 on communications from health agencies, according to the Associated Press.

“We count on the HHS especially to be transparent and a scientific voice so doctors and patients are informed about emerging and existing prevailing health trends,” Public Citizen’s Abrams said.

A page on increasing clinical trial participation for the LGBTQ+ community was removed as of Monday. It was last archived on Jan. 18

[….]

A page for the CDRH’s Health of Women Program was also removed as of Monday. It was last archived on Dec. 24, 2024. The program was started in 2016 to address sex- and gender-specific issues in medical technology design and performance.

Eileen Barrett, a hospitalist and president-elect of the American Medical Women’s Association, said having women and LGBTQ+ people represented in clinical trials “should be apolitical.”

“Nobody wants the patients to get worse care because we aren’t acknowledging the entire context in which they’re experiencing their health and also the way they experience healthcare delivery,” Barrett said.

Webpages were also down on the CDRH’s recent Home as a Health Care Hub initiative, including an announcement for the program and a listening session the agency held last year. The program was launched in April by Michelle Tarver, who was named CDRH director in October. The program is intended to provide resources for devices to be designed with a home environment in mind, starting with a focus on diabetes.

Another removed page referenced a virtual public meeting on real-world evidence slated for Jan. 30.

[….]

Zuckerman said the communications blackout makes a “bad impression,” raising questions about whether the public will be notified about important recalls or product approvals.

“I think there’s so much that needs to improve with transparency, and I see things going backwards,” Device Events’ Kinard added

To read the entire article in MedTech Dive, click here.

National Center for Health Research Comment on USPSTF Draft Recommendations on Cervical Cancer Screening

Uncategorized

 1. Based on the evidence presented in this draft Recommendation Statement, do you believe that the USPSTF came to the right conclusions?

  • Yes; I believe the USPSTF came to the right conclusions.
  • Somewhat; I believe the USPSTF came to the right conclusions in some ways but not in others.
  • No; I do not believe the USPSTF came to the right conclusions.
  • Unsure; I am not sure if the USPSTF came to the right conclusions.

Somewhat; I believe the USPSTF came to the right conclusions in some ways but not in others.

2. Please provide additional evidence or viewpoints that you think should have been considered.

Our main disagreement is that our review determined that the data are insufficient to conclude that HPV is superior to cytology for women ages 30-65, taking into consideration all patient outcomes, including diagnosis, overtreatment, survival, psychosocial impact, and costs.

We agree with the USPSTF statements about the high sensitivity of HPV testing, but the USPSTF statement underemphasizes the anxiety and overtreatment for women with a positive HPV test result from a transient infection. The major disadvantage of HPV testing is that a positive HPV result for women from 30-65 years is likely to result in a colposcopy. We therefore question whether HPV testing should be considered preferable to Pap cytology, since the two have comparable effectiveness for many women and Pap cytology avoids diagnosing transient HPV infections. Moreover, while HPV testing can identify more precancerous lesions earlier, its impact on reducing invasive cancer and improving survival is unclear and may depend heavily on follow-up care and screening adherence.

The ARTISTIC trial (Kitchener et al., 2009) found that HPV testing was more sensitive than cytology for detecting CIN3+ lesions in the initial round of screening. However, it did not demonstrate a significant reduction in invasive cervical cancer rates by the second round. Castle et al. (2018) demonstrates that while HPV testing detects more high-grade lesions earlier, it does not significantly reduce invasive cervical cancer rates or improve survival outcomes. Similarly, McCredie et al. (2008) demonstrated that while many high-grade lesions progress to invasive cancer if left untreated, a significant proportion regress spontaneously. These studies suggest that while HPV testing can identify more precancerous lesions earlier, its impact on reducing invasive cancer and improving survival may depend heavily on follow-up care and screening adherence.

In contrast, a pooled analysis looking at the results of 4 studies with a total of more than 170,000 patients, Ronco et al. (2014) found that HPV-based screening significantly reduced the incidence of invasive cervical cancer compared to cytology alone over a 6.5-year period.  The fact that patients enrolled in these 4 studies lived in Europe and Scandinavia could explain why these findings seem to contradict the Kitchener, Castle, and McCredie trials cited in our previous paragraph. It is possible that HPV testing may be more effective than cytology in countries where health care is free and very widely available. Overall, the results suggest that the incremental benefit of HPV testing over cytology is unclear but may be strongest in countries where access to care is not limited. These results do not justify considering it the preferred option for women between the ages of 30 and 65 in the U.S., given the increased costs, uncertain access to follow-up care, psychological stress, and patients’ desire to avoid the cost of potentially unnecessary procedures.

The importance of follow-up care is evident in studies like Dillner et al. (2008), which emphasized the critical need for systems to manage HPV-positive results effectively in order to avoid unnecessary interventions without compromising cancer prevention. Since colposcopies are invasive and more expensive and anxiety-producing than a cytology test, we strongly urge the USPSTF to specify that if HPV is used as the primary test, a positive HPV result should be followed by cytology as the next step before proceeding to colposcopy. This approach is supported by international guidelines such as those in the Netherlands and Australia. Specifically, the Dutch program incorporates cytology as a triage step following a positive HPV test to reduce unnecessary colposcopies, while maintaining sensitivity for clinically significant lesions (Rijkaart et al., 2012). Similarly, Australia’s National Cervical Screening Program transitioned to primary HPV screening with reflex cytology for non-HPV16/18-positive cases to improve cost-effectiveness and patient outcomes (Lew et al., 2017). Similarly, in the four countries studied by Ronco et al, for women whose initial screening was an HPV test, if the results were positive that was followed by cytology rather than colposcopy. If the cytology test was negative despite the positive HPV test, the women underwent a follow-up HPV test approximately one year later. These strategies show that cytology offers a balanced approach to triage, reducing unnecessary referrals after a positive HPV test, while maintaining detection rates.

In addition, the USPSTF draft does not sufficiently address the impact of self-collected HPV samples in real-world settings. Studies like Arbyn et al. (2014) and Polman et al. (2019) highlight logistical barriers, accuracy concerns, and the importance of robust follow-up systems.

References

Arbyn M, Verdoodt F, Snijders PJ, et al. Accuracy of human papillomavirus testing on self-collected versus clinician-collected samples: a meta-analysis. Lancet Oncol. 2014;15(2):172-183. doi:10.1016/S1470-2045(13)70570-9

Castle PE, Kinney WK, Xue X, et al. Effect of Several Negative Rounds of Human Papillomavirus and Cytology Co-testing on Safety Against Cervical Cancer: An Observational Cohort Study. Ann Intern Med. 2018;168(1):20-29. doi:10.7326/M17-1609

Dillner J, Rebolj M, Birembaut P, et al. Long term predictive values of cytology and human papillomavirus testing in cervical cancer screening: joint European cohort study. BMJ. 2008;337:a1754. Published 2008 Oct 13. doi:10.1136/bmj.a1754

Kitchener HC, Almonte M, Gilham C, et al. ARTISTIC: a randomised trial of human papillomavirus (HPV) testing in primary cervical screening. Health Technol Assess. 2009;13(51):1-iv. doi:10.3310/hta13510

Lew JB, Simms KT, Smith MA, et al. Primary HPV testing versus cytology-based cervical screening in women in Australia vaccinated for HPV and unvaccinated: effectiveness and economic assessment for the National Cervical Screening Program. Lancet Public Health. 2017;2(2):e96-e107. doi:10.1016/S2468-2667(17)30007-5

McCredie MR, Sharples KJ, Paul C, et al. Natural history of cervical neoplasia and risk of invasive cancer in women with cervical intraepithelial neoplasia 3: a retrospective cohort study. Lancet Oncol. 2008;9(5):425-434. doi:10.1016/S1470-2045(08)70103-7

Polman NJ, Ebisch RMF, Heideman DAM, et al. Performance of human papillomavirus testing on self-collected versus clinician-collected samples for the detection of cervical intraepithelial neoplasia of grade 2 or worse: a randomised, paired screen-positive, non-inferiority trial. Lancet Oncol. 2019;20(2):229-238. doi:10.1016/S1470-2045(18)30763-0

Rijkaart DC, Berkhof J, Rozendaal L, et al. Human papillomavirus testing for the detection of high-grade cervical intraepithelial neoplasia and cancer: final results of the POBASCAM randomised controlled trial. Lancet Oncol.2012;13(1):78-88. doi:10.1016/S1470-2045(11)70296-0

Ronco G, Dillner J, Elfström KM, et al. Efficacy of HPV-based screening for prevention of invasive cervical cancer: follow-up of four European randomised controlled trials [published correction appears in Lancet. 2015 Oct 10;386(10002):1446. doi: 10.1016/S0140-6736(15)00411-0]. Lancet. 2014;383(9916):524-532. doi:10.1016/S0140-6736(13)62218-7

3. How could the USPSTF make this draft Recommendation Statement clearer?

  • USPSTF’s statement should acknowledge and take into account the psychosocial and economic impacts of unnecessary colposcopies, particularly for low-income and underserved populations.
  • UPSTF should review and include well-designed studies on invasive cancer and survival outcomes tied to HPV testing versus cytology, or clearly state that such data are unavailable or inconclusive. Detection alone is not a meaningful endpoint without demonstrated survival benefits.
  • USPSTF should provide clearer guidance on triage pathways, emphasizing cytology as the next step after a positive HPV result instead of immediate colposcopy.

4. What information, if any, did you expect to find in this draft Recommendation Statement that was not included?

  • A more comprehensive review of comparative data on invasive cancer and survival for HPV testing and cytology as primary screening strategies.
  • More nuanced recommendations for women over 65, which consider individual risk factors such as new sexual partners or immunosuppressive conditions.
  • Greater detail on the feasibility and cost-effectiveness of implementing self-collected HPV testing in the U.S. in the real world, not just in research or clinical settings, including follow-up protocols to prevent gaps in care.

5. What resources or tools could the USPSTF provide that would make this Recommendation Statement more useful to you in its final form?

The USPSTF could enhance the utility of this Recommendation Statement by providing:

  1. Decision-making algorithms or flowcharts for clinicians and patients that clearly outline the steps following various screening outcomes (e.g., HPV-positive, cytology-positive, or combined). This would be particularly helpful in reinforcing the role of cytology as a triage step before colposcopy.
  2. Cost-effectiveness analysis summaries comparing different screening strategies (e.g., HPV testing alone, Pap cytology alone, and co-testing) in terms of cancer detection, survival outcomes, and healthcare utilization.
  3. Guidance on self-collection implementation, including best practices for ensuring accuracy and follow-up care, particularly for underserved populations.
  4. Risk calculators or interactive tools to help patients better understand their individualized risk and the potential benefits or harms of different screening intervals or modalities.

6. The USPSTF is committed to understanding the needs and perspectives of the public it serves. Please share any experiences that you think could further inform the USPSTF on this draft Recommendation Statement.

From a clinical perspective, patients often express significant anxiety about abnormal HPV results, particularly when the next step involves immediate colposcopy. This underscores the need for clear communication about the low risk of invasive cancer in many HPV-positive cases and the rationale for using cytology as an intermediate triage tool. Additionally, underserved populations face barriers such as lack of follow-up after abnormal results or inadequate access to colposcopy services. Unfortunately, when patients are concerned about cost or access associated with a positive HPV test, they may delay follow-up until their condition is much worse. In such cases, the absence of robust systems for patient navigation exacerbates disparities in cervical cancer outcomes.

Based on our experiences with patients, it is especially essential to integrate follow-up protocols into any recommendations involving self-collection or HPV primary screening.

7. Do you have other comments on this draft Recommendation Statement?

Yes, there are additional points to consider:

  1. The Recommendation Statement could benefit from a stronger focus on survival outcomes rather than cancer detection alone. Current evidence does not consistently demonstrate that HPV testing translates into better survival outcomes compared to cytology. For example, the ARTISTIC trial found no significant reduction in invasive cancer rates despite increased lesion detection with HPV testing (Kitchener et al., 2009).
  2. The USPSTF should provide greater emphasis on individualized screening decisions, especially for women over 65, where risk factors like recent sexual activity or changes in immune status may necessitate continued screening despite adequate prior testing.
  3. To ensure equitable care, the Statement should explicitly address the logistical challenges of access to colposcopy and to implementing self-collected HPV testing in real-world settings, including the importance of integrating results into electronic health records (EHRs) and ensuring timely follow-up.
  4. Lastly, the draft should clarify the USPSTF’s position on triage pathways for HPV-positive results. Cytology following HPV-positive results should usually serve as an intermediate step before colposcopy, and should be described as the preferred strategy after a positive HPV because it is  more cost-effective and patient-centered.

In debate over obesity medications, FDA shifts toward importance of drugs in subtle ways

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Elaine Chen, STAT News, January 10, 2025

For years now, companies behind weight loss drugs like Wegovy and Zepbound have been trying to convince the medical community and the public that obesity is a disease and medications are the answer. It seems the Food and Drug Administration has now shifted its perspective, too.

This week, amid a slew of new recommendations that the FDA released ahead of President-elect Trump’s inauguration, the agency posted draft guidance on obesity clinical trials, the first time it has done so since 2007.

The new draft calls obesity “a chronic disease,” whereas the previous guidance called it “a chronic, relapsing health risk.”

It mentions the importance of lifestyle interventions less than the previous guidance, omitting a reference to lifestyle modification being seen as “the cornerstone of overweight and obesity management.” It also takes a less conservative view of how companies should test drugs in the pediatric population, removing recommendations that drugmakers should first conduct studies in higher-risk adolescents than other children.

Draft guidance documents issued by the FDA are not binding, but revisions, even subtle, provide a look into the agency’s stances; they also have real-world implications for how experimental drugs and devices are assessed and approved.

The changes reflect “a cultural shift” around obesity medications, said Diana Zuckerman, president of the nonprofit National Center for Health Research, which analyzes and explains health research to the public. As a result, the new guidance “seems more favorable to the drug companies.”

Some doctors welcomed the changes, saying that the FDA now appears to be treating obesity drugs similarly to treatments for conditions like hypertension and diabetes; in none of those cases does the agency indicate it expects patients to wait and try to alter their behavior before trying medications. Other experts, however, were concerned that the changes seemingly assign less significance to lifestyle changes.

“I think it’s a missed opportunity to show a more neutral stance on weight loss strategies,” Zuckerman said.

In a statement, the FDA said that it “continues to recognize the important role of lifestyle intervention in the management of patients with obesity.” The new guidance, like the previous one, still says that during trials, drugs should be studied as an add-on to lifestyle intervention.

The reactions mirror the broader debate over whether new weight loss drugs, and drugmakers’ marketing efforts, will lead to an over-medicalized approach to addressing obesity rates. Pharma companies have been pushing the message that obesity is a biological disease that requires treatment with drugs, in both overt and subtle ways. Novo Nordisk has even funded medical school curricula on obesity.

Some doctors are also concerned that the FDA’s new guidance continues to place too much emphasis on weight instead of overall health. Like the previous guidance, it says percentage weight loss is the primary endpoint for assessing obesity drugs in clinical trials, rather than changes in body composition and fat mass specifically.

It’s not clear if the FDA under Trump would take a different approach to regulating obesity drugs. Some of his allies, notably Robert F. Kennedy Jr., Trump’s pick to lead the Department of Health and Human Services, which oversees the FDA, has criticized the proliferation of weight loss drugs and emphasized the importance of lifestyle changes instead.

Still, the revisions show just how much arguments about the importance of obesity drugs have permeated the medical establishment.

Less discussion of lifestyle changes

The previous guidance clearly emphasized the role of lifestyle changes in weight loss, saying: “Lifestyle modification, consisting of changes in patterns of dietary intake, exercise, and other behaviors, is considered the cornerstone of overweight and obesity management. Because all drug and biological therapies impose some risk for adverse events, the use of a weight-management product should be contemplated only after a sufficient trial of lifestyle modification has failed and the risks of excess adiposity and the anticipated benefits of weight loss are expected to outweigh the known and unknown risks of treatment with a particular weight-management product.” This language is not in the new guidance.

 

[….]

However, William Dietz, former director of the Division of Nutrition, Physical Activity, and Obesity at the Centers for Disease Control and Prevention, said lifestyle changes should still be the primary way to address obesity, even if drugs play a key role.

“I’m surprised it’s been omitted, and it’s an important omission that needs to be rectified,” said Dietz, who is now a professor in the department of exercise and nutritional sciences at George Washington University.

Less stringent recommendations for pediatric trials

The new guidance also removes the recommendation that for pediatric trials, companies should limit initial studies to adolescents ages 12 to 16 and to higher-risk children who have a weight-related condition like type 2 diabetes or hypertension.

The new draft does not specify an order in which companies should conduct pediatric trials — only that they should conduct separate trials for adolescents ages 12 and up and for younger children ages 6 to 11.

Tom Robinson, a professor of pediatrics at Stanford University, said that while it’s important to eventually test drugs in younger children, he would prefer they first be tested in older teenagers who have gone through puberty. From there, “carefully move down, because the unknowns are much greater when you’re dealing with children who are still growing and developing,” he said.

[….]

Continued focus on weight, not body composition

The medical community has been shifting away from using weight and body mass index as the sole metrics to assess patients with obesity, with the American Medical Association last year asking doctors to de-emphasize the use of BMI in clinical care.

[….]

However, in its new guidance, the FDA still defines obesity using BMI and primarily looks at overall weight loss when assessing drugs. It does say that companies that want to specifically get approval on body composition to consult with the agency.

 

Steven Heymsfield, a professor of metabolism at Pennington Biomedical Research Center, would have liked to have seen the agency propose a range of endpoints that companies could prioritize in general obesity trials, such as a change in body fat and waist circumference, in addition to overall weight loss.

Heymsfield, who’s been involved in research on a drug that aims to preserve muscle mass, also said he thought the FDA should have taken loss of lean mass more seriously as a potential concern.

[….]

To read entire article in STAT News, click here.

NCHR Public Comment on Communications From Firms to Healthcare Providers Regarding Scientific Information on Unapproved Uses of Approved Medical Products

Uncategorized

We appreciate the opportunity to comment on the FDA’s guidance: “Communications From Firms to Healthcare Providers Regarding Scientific Information on Unapproved Uses of Approved Medical Products, Questions and Answers.”

The National Center for Health Research (NCHR) is a nonprofit think tank that conducts, analyzes, and scrutinizes research on a range of health issues, with a particular focus on which prevention strategies and treatments are most effective for which patients and consumers. Our largest program is the Cancer Prevention and Treatment Fund. We do not accept funding from companies that make products that are the subject of our work, so we have no conflicts of interest.

Research indicates that off-label use of medications is common, that physicians prescribing unapproved uses often are unaware that they are doing so, that evidence of safety and efficacy are usually lacking, and that patients are often harmed by off label uses, financially and in terms of their health. That is why it is essential that the FDA provide unambiguous guidance to industry about how to provide information to healthcare providers about unapproved uses of approved medical products.

NCHR agrees with the FDA that any communication between drug firms and healthcare providers regarding scientific information on the unapproved uses of an otherwise approved medical product should be factual and unbiased. However, even when communication is based on high-quality scientific evidence, including randomized, double-blinded controlled superiority trials, the interpretation of the research results can be biased and misleading. That is why all such communication should be subject to regulatory review, as well as clear explanations by the firms to the providers that the product is not approved by the FDA for that purpose, either because the company has not provided evidence to support the off-label use, or because FDA considered any evidence that the company provided to the agency to be insufficient to warrant that off-label indication.

We agree that the FDA should reject the use of scientific communication based on case reports, early-stage development reports, or studies that lack an adequate comparison or control group, even when these limitations are disclosed. Data gathered from these types of studies are insufficient to permit a thorough clinical evaluation for the unintended use of a medical product. Moreover, since not all physicians have expertise in study design and data interpretation, providing such information could easily be misleading or misunderstood.

We strongly support FDA’s proposal to limit the use of presentations to communicate scientific information on the unapproved uses of approved medical products. Because there is rarely enough time to carefully examine the evidence in PowerPoint or other oral presentations, they are unlikely to present information in the full context needed for healthcare providers to interpret the strengths and weakness of the data provided. Presentations may also unintentionally misrepresent or manipulate results, by using figures and graphs that do not fully represent the data. Moreover, the FDA should oppose any communication that uses marketing techniques, since such techniques often unduly influence and bias the audience’s understanding of the risks and benefits of the medical product being considered. All communication should focus on the scientific facts, so that the information will be accurate and understood based on the objective evidence, and healthcare professionals can then accurately share that information with patients. That will enable patients and their providers to make well-informed decisions.

We agree with the FDA that firms should be required to provide a statement identifying that the off-label use of the medical product has not been approved by the FDA and the safety and effectiveness has not been established. A statement acknowledging any serious or life-threatening risks that may be associated with the medical product should also be included, whether the risks have been associated with the approved or unapproved uses. Additionally, a declarations and disclosures statement should be included in these communications that acknowledges investigators who contributed to the design and publication of the study and also had financial ties to the company, whether as employees, consultants, stockholders, researchers, guest speakers, or who received compensation from the firm for any reason. Declarations and disclosures will provide transparency about a financial conflict of interest or the appearance of a conflict of interest that may have affected the design, conduct, or reporting of the research. This will facilitate a healthcare provider’s accurate evaluation of the scientific information provided and awareness of any apparent conflicts of interest or bias.

Lastly, the communication standards specified in this guidance should be consistently and strongly reinforced by the FDA. We recommend that the FDA provides clear instructions encouraging clinicians to report firms that fail to comply with scientific communication standards provided in this guidance. Reporting mechanisms should be made easily accessible and user-friendly for providers and any firms in violation should be publicly reported on the FDA website. This will help ensure that firms incorporate the communication recommendations provided by the FDA and help ensure that clinicians have the information they need to make evidence-based decisions that get past the hype of promotional materials that erroneously purport to be scientific evidence. The bottom line is that transparency in the process and regarding firms that do not comply with the requirements for accuracy and transparency will help safeguard patients from ineffective and unsafe uses of medical products. Given that the FDA frequency distributes press releases to announce the approval of new medical products, it is only right that the FDA be as willing to distribute press releases when companies inappropriately promote unapproved uses or when specific unapproved uses are found to be harmful.

Trump’s pick for FDA to test ‘due diligence’ of Agency’s science

In the News, News Stories & Editorials, We're In the News

Nyah Phengsitthy, Bloomberg Law, November 25, 2024

Marty Makary, an outspoken critic of the nation’s food and drug regulator, stands to shake up the FDA’s standards in science and decision-making under President-elect Donald Trump.

The Johns Hopkins surgeon selected Nov. 22 by Trump to lead the US Food and Drug Administration may have laid out his blueprint for a potential agency overhaul if confirmed as commissioner—and it starts with his criticisms over vaccine policy, food safety, and the pharmaceutical industry.

Makary has taken numerous shots at FDA decisions, including the agency’s approval of Covid-19 vaccines by Moderna Inc. and Pfizer Inc., its “cozy relationship” with drug manufacturers, and the approval of a drug to treat Alzheimer’s. He’s also offered judgment on the nation’s food supply, questioning the various chemicals in foods and infant formula.

While some of his opinions have drawn opposition, his critiques put to practice could reshape areas of the agency that have come under scrutiny, health policy experts say. His challenge on vaccine approvals, food safety, and the status quo ideas in the medical establishment signal a commissioner who won’t allow the agency to lower its standards and will tap more into science and decision-making.

“A lot of what he’s been talking about are things we need to be thinking about,” said Diana Zuckerman, president of the National Center for Health Research. “When you have somebody who’s outspoken on the side of public health, I think that’s something we should hear.”

[….]

“Dr. Makary seems like a person who could be persuadable by an evidence-based argument,” said Peter Lurie, president of the Center for Science in the Public Interest and former associate commissioner for public health strategy and analysis at the FDA.

“But the most consistent through-line between the HHS, CDC, and FDA nominees seems to be being vaccine-skeptical or worse.”

‘Sticking to the Science’

Though it’s unclear how Makary’s concerns will play out as chief, he could demand the agency carry out deeper examinations and assessments in its everyday decisions.

The FDA in recent years has come under fire for some scientific conclusions and the information used to back its regulatory decisions. This includes its authority over e-cigarettes, the abortion pill mifepristone, laboratory-developed tests, and major drug approvals.

“You want to have that person very much sticking to the science, so that we know that these new medicines, medical devices, whatever comes to the market, is truly safe and effective,” said Reshma Ramachandran, an assistant professor at Yale School of Medicine.

“He has a pretty profound background in research, so that gives me some comfort knowing he will hopefully continue to follow the science in making decisions.”

Makary also “recognizes the value of not letting approval standards dip dangerously low,” said Holly Fernandez Lynch, a professor of medical ethics at the University of Pennsylvania. She pointed to when he criticized the FDA for approving Alzheimer’s drug aducanumab despite safety concerns.

The author and professor has taken issue with the lack of transparency between the agency and pharmaceutical industry. He’s also a critic of the Orphan Drug Act, which allows manufactures to secure protections for rare disease drugs when they hit the market.

“He wants to make sure that the agency’s decisions are being made from a scientific perspective, and not being unduly influenced by the sponsors who are bringing forward the products,” Ramachandran said. “I’m hoping he’ll maintain that thinking to make sure the agency is doing its due diligence in its work.”

[….]

Food Safety

Makary’s agenda may test the FDA’s oversight on food safety—another area that has been scrutinized in recent years.

He has called the food supply “poisoned” with “highly addictive chemicals.” He’s also scrutinized the amount of seed oils in infant formula, and questioned why Froot Loops are sold with different food dyes in the US than in Canada.

His appointment would come as the FDA rolls out its Human Foods Program, which was created under the agency’s largest reorganization.

Notably, the program is in the midst of establishing a framework to assess chemicals in food already on the market—a move that was criticized for being conducted through an ad hoc basis and largely behind closed doors.

Makary could take “positive steps” in regulating and eliminating “harmful components that are still allowed in food, supplements, food containers and packaging,” according to Ana Santos Rutschman, professor at the Charles Widger School of Law at Villanova University.

“Among all the nominations so far in the public health space, this is the candidate with the strongest credentials,” Rutschman said. “And I think that there is, at least for now and in theory, room for some positive developments at the FDA.”

To read the entire article in Bloomberg Law, click here.

Vivek Ramaswamy’s crusade to change FDA could boost biotech, and himself

In the News, News Stories & Editorials, We're In the News

Daniel Gilbert, The Washington Post, November 25, 2024

Vivek Ramaswamy, an outspoken ex-biotech executive turned fierce critic of the industry’s main regulator, is now in a position to reshape the agency he derides as the “Failed Drug Administration” in ways that could benefit him personally.

Newly tapped by President-elect Donald Trump to co-lead an initiative to slash the federal bureaucracy, Ramaswamy has heaped criticism on the Food and Drug Administration for “unnecessary barriers to innovation.” At the same time, the company he founded, Roivant Sciences, is pursuing studies for three drugs that, if positive, could land before the FDA during Trump’s second term. His stock in Roivant is worth about $670 million.

Ramaswamy argues that the FDA should err on the side of approving promising therapies faster and then monitoring their effects after doctors start prescribing them. The agency should place “greater emphasis on post-approval surveillance for safety issues to protect patients, rather than adding time and cost to innovative development,” he said in a statement. He highlighted the FDA’s standard requirement of two trials for approval and suggested a single trial — which would generally save biotech firms time and money — would be adequate.

Ramaswamy, with billionaire Trump adviser Elon Musk, is spearheading the “Department of Government Efficiency,” an outside-government project to streamline bureaucracy and carry out “mass head-count reductions,” the two wrote in a Wednesday op-ed. Ramaswamy left Roivant’s board in February 2023 when he launched his presidential campaign but is still one of its largest shareholders.

“It’s an obvious conflict of interest,” said Diana Zuckerman, president of the nonpartisan think tank National Center for Health Research, who points out that the FDA has already lowered its standards considerably to speed novel drugs to market. “Some people might think, ‘He’s a knowledgeable person.’ He’s a knowledgeable person with a vested financial interest in what he’s saying.”

In an interview, FDA Commissioner Robert Califf said he knows and respects Ramaswamy but pushed back on some of the entrepreneur’s harshest criticisms, such as once questioning the need for the agency. “We tried that,” he said, pointing as an example to the drug thalidomide that caused birth defects in babies in the 1960s, “which is why the FDA exists in its current form.”

“Almost every additional authority at FDA has been because of a catastrophic public health event that harms people,” he said.

Califf defended the two-trial standard, particularly for new drugs when there are already effective therapies available, while emphasizing that the FDA frequently accepts less evidence for potentially life-changing therapies. As for Ramaswamy’s financial stake in biotech, Califf said, “at FDA, you’re not allowed to make decisions about industries in which you have a vested interest.” He added, “I would just say, the amount of money he has invested and what’s at stake speaks for itself.”

[….]

Of all novel drugs approved in 2020, more than half relied on a single such trial, one study found.

On Saturday, Ramaswamy praised Trump’s choices to lead the FDA and other health agencies, saying he had met with them and “it’s clear they’re serious about reducing cost & they understand innovation is a key part of the solution.” Marty Makary, whom Trump tapped to lead the FDA late Friday, has emerged as a forceful critic of the agency’s culture, faulting it in a 2021 op-ed for a “counterproductive rigidity and a refusal to adapt.”

Ramaswamy made his name as a wunderkind biotech analyst on Wall Street while earning a law degree at Yale, before striking out on his own as an entrepreneur. He told Forbes for a 2015 cover story that Roivant would be the “Berkshire Hathaway of drug development.”

[….]

Ramaswamy pulled off what was at the time, in 2015, the largest public offering in biotech, raising $360 million with the listing of Axovant, a Roivant subsidiary developing an Alzheimer’s drug. Controversy followed as a clinical trial failed to show a benefit and the stock value collapsed.

Roivant has gone on to develop several drugs that won FDA approval, but it has made a bigger splash for its savvy dealmaking.

[….]

Roivant executives have told investors its pipeline of experimental drugs could someday be worth $10 billion a year in sales. Ramaswamy holds a roughly 7 percent stake in the company, in addition to stock options to purchase millions more shares.

Trial results for two drug candidates — one to treat an autoimmune condition that causes a skin rash and muscle weakness, another for an eye inflammation disease — are expected in the second half of 2025, executives have said. The trial for the autoimmune condition is designed to support FDA approval without a second one, the company has said.

Roivant declined to comment.

Ramaswamy criticized the FDA during his failed bid for the GOP presidential nomination, a campaign where he sought to distinguish himself with a provocative style on an array of subjects. He called the agency “corrupt” and its actions “hypocritical, harmful & unconstitutional” in July 2023.

After he endorsed Trump, he continued to slam the agency. “It’s not at all obvious that we’re better off for having an FDA at all,” he said in May, dedicating an episode of his podcast to the issue. He suggested that the private market could be a better judge of what patients should trust, similar to how customers rely on J.D. Power ratings to buy cars. “The FDA has actually crowded out the rise of those alternative intermediary institutions,” he said.

[….]

Several academic scholars interviewed for this story said they disagree with Ramaswamy’s contention that conducting two major clinical trials to replicate results is unnecessary.

Sanket Dhruva, a professor at the University of California at San Francisco School of Medicine, acknowledged that clinical trials are expensive and add to the cost of developing new medicines. Still, he said, “What about costs that are passed on to the health-care system using tests and treatments that are relatively unproven?” He argued that approving less-studied drugs can give patients false hope or cause them harm and add to higher insurance premiums.

[….]

Read the full article in The Washington Post here.

What Trump’s election win could mean for AI, climate and health

In the News, News Stories & Editorials, We're In the News

Jeff Tollefson, Max Kozlov, Mariana Lenharo, and Traci Watson, Nature, Nov 8, 2024

From repealing climate policies to overturning guidance on the safe development of artificial intelligence (AI), Republican Donald Trump made plenty of promises during his presidential campaign that could affect scientists and science policy. But fulfilling all of his pledges won’t be easy.
Trump, now the US president-elect for a second time, will have some advantages as he re-enters the White House in January. The first time he took office, in 2017, his victory was a surprise, and many government watchers who spoke to Nature say he didn’t have a solid plan. By contrast, the Trump administration that enters office next year will be better prepared, and Trump himself is likely to face fewer checks on his power now that he has consolidated control over the Republican establishment, says Matt Dallek, a political historian at George Washington University in Washington DC who studies the evolution of the modern conservative movement.
But that doesn’t mean he will be able to do as he pleases, Dallek adds. “There’s a kind of revolutionary sweep to a lot of Trump’s promises that may collide with the messy reality of implementation.”
Here Nature talks to policy and other specialists about what might be in store on a range of science issues during a second Trump administration.
[….]
Health
In the weeks leading up to the US election, Trump teamed up with political figure Robert F. Kennedy Jr on a platform promising to “make America healthy again” by tackling the root causes of chronic diseases, removing toxic substances from the environment and combating corporate corruption. Trump has said that he will let Kennedy, who has questioned the effectiveness of vaccines, “go wild on” health, unnerving public-health and health-policy researchers.
It remains to be seen whether Trump will appoint Kennedy to a position such as director of US Health and Human Services (HHS) — or whether the US Senate would approve such a move — but it’s clear that Kennedy will have Trump’s ear on health issues.
Georges Benjamin, the executive director of the American Public Health Association in Washington DC, worries about Kennedy’s role in the new administration because he has long cast doubt on the vaccine-approval process, threatening to undermine confidence in the jabs and cause a resurgence in illnesses such as measles. “People will get sick and die because of the confusion around vaccines, if [Kennedy and Trump] implement some of the things they verbalize,” he says.
Some of Kennedy’s goals, such as cracking down on ties to industry at regulatory agencies such as the US Food and Drug Administration, are good, says Diana Zuckerman, president of the National Center for Health Research, a non-profit think tank in Washington DC. But those goals don’t jibe with what occurred during the first Trump administration, when Trump installed people in important health posts who had close industry ties, such as former HHS director Alex Azar, so it’s hard to know what will happen, she says.
Considering Trump’s isolationalist approach and his past comments criticizing the World Health Organization, support for global health is also likely to be “greatly scaled back” during Trump’s second term, says Ezekiel Emanuel, a bioethicist and long-time observer of the US biomedical funding landscape at the University of Pennsylvania in Philadelphia. The United States is “the key player” in the funding of global-health initiatives, says Emanuel. This includes, for instance, a programme that aims to end the global AIDS epidemic. So it’s “hard to be optimistic” about the future, he adds.
Foreign science partnerships
During Trump’s first term, his administration barred people from half a dozen countries that it said were “compromised by terrorism” from entering the United States and implemented an anti-espionage programme called the China Initiative that led to the arrests of a number of scientists of Chinese heritage. Although the Biden administration overturned the travel ban and ended the China Initiative, federal officials have continued efforts to guard against foreign interference in US research.

Specialists says it’s unclear whether the second Trump administration will revive the China Initiative, although the Republican-led US House of Representatives advanced legislation in September that would do so. But a reinstatement of the travel ban is likely, says Adam Cohen, a lawyer at Siskind Susser in Memphis, Tennessee, who focuses on academic immigration and who says the president has broad authority to institute such policies.
Like the first Trump administration, the new one will probably clamp down on granting visas to foreign researchers and students from some countries, says Jennifer Steele, an education-policy researcher at American University in Washington DC. Policies that make it harder for international and US researchers to meet would also make it harder for new scientific collaborations to arise, says Caroline Wagner, a specialist in science, technology and international affairs at the Ohio State University in Columbus. That’s because such partnerships are fuelled by face-to-face contact. “Collaborations don’t begin with people just e-mailing each other across the miles,” she says.
But there might be one bright spot on the collaboration front, at least for US–China partnerships. Denis Simon, a non-resident fellow at the Quincy Institute for Responsible Statecraft, a foreign-policy think tank in Washington DC, thinks that a crucial pact governing US–China scientific cooperation that has been expired for the past year is likely to be signed by the Biden administration before Trump’s second inauguration in January. Although a renewed agreement would probably be more limited in scope owing to increased US–China tensions, its existence would show that “both governments give their blessing” to collaborations, Simon says.
Read the full article in Nature here.

Statement of Dr. Diana Zuckerman At the FDA General and Plastic Surgery Devices Advisory Panel on ProSense Cryoablation System

Policy, Testimony & Briefings

November 7, 2024

I’m Dr. Diana Zuckerman, president of the National Center for Health Research. Our center is a nonprofit public health research center that scrutinizes the safety and effectiveness of medical products, and we don’t accept funding from companies that make those products so we have no conflicts of interest.

We thank FDA and this Committee for your important work. My expertise is in clinical trial design and data analysis and as a breast cancer survivor. Prior to my current position, I was a post-doc in epidemiology and public health at Yale Med School, and was a faculty member and PI at Yale and Harvard.  I also investigated FDA approval standards while working in the US Congress, HHS, and the White House. I’m on the Board of the nonprofit Alliance for a Stronger FDA, which educates Congress about the need to financially support the essential work of the FDA.

As a survivor of T1 breast cancer, I appreciate the desire for less invasive treatment. But I am concerned that this cryoablation system was studied in a small, one-arm trial instead of a larger randomized clinical trial. We also share FDA concerns about serious data irregularities– including missing data that weren’t analyzed correctly — and lack of racial diversity of the patients in the study.

A breast cancer diagnosis is a traumatic experience and our research center has talked to hundreds of patients who tell us how overwhelming it is to consider all their treatment options. What matters most is overall survival, but recurrence also matters. Quality of life is very important but requires validated tests to be meaningful, and that was not done here. Most important, since 5-year recurrence is low for these kinds of early-stage breast cancers regardless of treatment, we can’t know the long-term success without a larger, longer term, randomized trial.

On a personal note, I went into my surgery with a diagnosis of DCIS. The tiny invasive cancer was found only as a result of the surgical specimen. Very small tumors can be difficult to find, and a randomized trial with post-market follow-up for a longer period of time would make it possible for patients to make better informed decisions, choosing the treatment that’s best for them.

Breast cancer treatment teams try to give patients the best possible information, but many patients tell us they are confused by the treatment options. They’re confused by the implications of terms like recurrence, disease-free survival, overall survival, primary and secondary cancer.

In addition, we also need to be concerned about how a new treatment that does not require surgery might be inappropriately promoted and used for larger or higher-risk tumors than those in the indication, and an indication that includes women who are younger than those studied. That use might be off label or included in the label, so if this product is approved the label should clearly specify what the data indicate and the indication should be consistent with that. We also urge FDA to require a short, simple patient checklist to maximize informed consent.

After her presentation, Advisory Panel members asked Dr. Zuckerman two questions as part of the panel discussion. Her answers are included below.

A: Thank you for asking about the patient checklist. FDA has sometimes used checklists to help provide understandable information about a medical device. Checklists should include facts that are short, simple, and easy to understand. For example, a checklist for this Cryoablation System could include facts such as:

1. “Research shows that _% of women using this product have a recurrence of breast
cancer within 5 years, compared to _% for women undergoing lumpectomy surgery.

2. There are no studies indicating how often recurrence of breast cancer occurs within 10 years of using this product.

The patient would initial each statement to show that she read it, and the physician should also sign it to show their explanations were consistent with the checklist. Keep in mind that informed consent is a process, not just a document, and it is important that the physician not make statements inconsistent with the checklist.

A: Thank you for asking why I said randomized controlled clinical trials were needed to help women make informed choices. We all know that randomized controlled trials are the gold standard and there is no reason why that wasn’t done with this product, since the alternative is clear: the standard of care is lumpectomy. You’ve heard that women wouldn’t want to participate in a randomized trial if they could choose cryoablation instead, but that is not true if they were accurately told that this is a clinical trial, and we are conducting it to find out whether or not Cryoablation is as effective as surgery. Patients need to know that it is study being done to find out if the product is effective; they should not be told that it is as effective as surgery when that is not known.