Category Archives: Legislation

We Comment to FDA on the Draft Guidance Postmarketing Studies and Clinical Trials: Determining Good Cause for Noncompliance with Section 505(o)(3)(E)(ii) of the Federal Food, Drug, and Cosmetic Act

Legislation

September 12, 2023

Docket No. FDA-2023-D-0559

We appreciate the opportunity to comment on the Food and Drug Administration (FDA) proposed guidance: Postmarketing Studies and Clinical Trials: Determining Good Cause for Noncompliance with Section 505(o)(3)(E)(ii) of the Federal Food, Drug, and Cosmetic Act Guidance for Industry.

We are 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. We do not accept funding from companies that make products that are the subject of our work, so we have no conflicts of interest.

Noncompliance with required post-market studies (PMRs) is a serious problem that undermines FDA’s authority and the public trust in FDA decision-making. We support FDA’s efforts to ensure clarity and transparency regarding situations when noncompliance with postmarket requirements is acceptable.  These situations should be rare; the more exceptions that are made, the more noncompliance becomes harmful to patients and unfair to companies that comply.

The PMRs that are the focus of this draft guidance are typically required following adverse events that have been reported to the FDA resulting in a serious enough event to warrant further examination into the safety and effectiveness of the drug. Any delay in this process places patients at undue risk and it is FDA’s responsibility to ensure that applicants avoid delays.

We understand this guidance document is specifically referencing non-compliance of PMRs which are not required as a condition of accelerated approval. However, we strongly recommend issuing similar guidance for applicants using this pathway.

We agree that applicants should continue to report regular updates to the FDA throughout the completion of the PMRs. The timelines and milestones established are agreed to by both the applicant and the FDA and should be adhered to. We appreciate the detail provided by FDA in the draft guidance stressing the importance of maintaining regular updates and providing multiple opportunities for applicants to inform the agency of missed milestones. These details, along with specific examples of what would or would not be considered good cause for non-compliance, should minimize overall non-compliance with the regulations. Documentation of delays is not sufficient to justify noncompliance, especially if the delays were foreseeable and avoidable and could suggest inadequate efforts to complete the study as was agreed to.

We support the process described in the guidance for applicants to correct circumstances that led to non-compliance with the agreed upon PMRs; however, we urge that the description of the actions taken by the applicant to address these issues be more explicit and less subjective. The guidance document states that the “FDA considers an applicant to have undertaken appropriate action if the applicant promptly develops and implements a reasonable plan to correct the underlying circumstance(s) leading to the PMR noncompliance” (emphasis added). The guidance document describes the term “promptly” as something the FDA will determine on a case-by-case basis. This is too vague; the FDA should clearly define the agency’s standards by providing examples of what could be considered inappropriate delays that will warrant escalation of actions taken by the agency. We also strongly urge that the FDA take into consideration if a company has a track record of delays in satisfying PMRs, regardless of whether the company’s justifications for those delays seem reasonable. The FDA should scrutinize the reasons given to determine if a company’s track record of delays show a pattern of making commitments to the FDA that the company has shown it is unlikely to meet. This would indicate that what might individually seem like justifiable delays may instead be based on a pattern of foreseeable and preventable delays.

As noted above PMRs which are required as a condition of accelerated approval warrant similar guidance. There have been unacceptable delays in postmarket trials for drugs granted accelerated approval status. More than 280 drug applications have been awarded accelerated approval since the program began; at least 100 of those applications still have incomplete confirmatory trials.1 Approximately 35 percent have at least one trial past its original planned completion date.1 A recently published journal article pointed out that Exondys 51, for Duchenne Muscular Dystrophy, was granted accelerated approval in 2016 with the PMR results required in 2020. Instead, that post-market study was not started until 2020 and FDA granted an extension until 2024, while also granting accelerated approval to 3 other drugs made by the same company, none of which have yet submitted their post-market studies.2 As a result of these delays, patients, insurance companies, and the Medicaid program have paid billions of dollars for treatments that have never been proven to work. This is unfair to patients and their families and threatens the financial integrity of Medicaid programs in States that have been subject to these expenses. We strongly urge that the FDA issue guidance about compliance with PMR for drugs granted accelerated approval before the end of 2023.

1.U.S. Department of Health and Human Services: Office of Inspector General. (2022). Delays in Confirmatory Trials for Drug Applications Granted FDA’s Accelerated Approval Raise Concerns. https://oig.hhs.gov/oei/reports/OEI-01-21-00401.asp#:~:text=WHAT%20WE%20FOUND,104%20have%20incomplete%20confirmatory%20trials.

2. Liam Bendicksen, Diana M. Zuckerman, Jerry Avorn, et al. (2023). The Regulatory Repercussions of Approving Muscular Dystrophy Medications on the Basis of Limited Evidence. Ann Intern Med. doi:10.7326/M23-1073

NCHR Comments on FDA’s Survey on Quantitative Claims in Direct-to-Consumer Prescription Drug Advertising

Legislation, Policy

 

June 26, 2023

The National Center for Health Research (NCHR) appreciates the opportunity to submit public comments on the notice by the Food and Drug Administration regarding their Survey on Quantitative Claims in Direct-to-Consumer (DTC) Prescription Drug Advertising.

NCHR is a non-profit think tank that conducts, analyzes, and scrutinizes research on a range of health issues, with particular focus on which prevention strategies and treatments are most effective for which patients and consumers. We do not accept funding from companies that make products that are the subject of our work, so we have no conflicts of interest.

We strongly support the efforts of the Office of Prescription Drug Promotion (OPDP) to protect public health by conducting research to evaluate patients’ understanding of quantitative information provided in prescription drug advertising. We work closely with patients and consumers and are well aware that many people do not understand quantitative claims made in drug advertisements.1 The information collected in this survey is essential to ensure the public is able to comprehend drug information in order to make informed medical decisions.

We appreciate the clear example provided in the notice regarding the type of information FDA is seeking to collect (i.e. claims describing medians). Some of the statements included were clear and direct (e.g., “People treated with Drug X lived for a median of 8 months” in combination with the explanation that “In people receiving Drug X, this means that about half lived more than 8 months and about half lived less than 8 months”). Research to evaluate patients’ understanding of such explanations will provide crucial information about individuals’ level of comprehension regarding quantitative information.  

We strongly recommend that determining patients’ and consumers’ comprehension of information regarding relative risk, absolute risk, relative benefit, and absolute benefit should also be evaluated by the FDA in this survey. For example, how does the public understand a statement that a drug reduces the relative risk of recurrence by 37% or increases the absolute chances of 5-year survival by 3%? Information about relative risk or relative benefit is often used in advertising because those numbers are inevitably larger and seem more impressive than the absolute difference in risk or benefit. According to the FDA’s own research, 65% of physicians believe DTC ads confuse patients about the relative risks and benefits of prescription drugs.2 Unfortunately, patients are not the only ones confused by these statistics.

The FDA notice states that survey questions will be informed by consumer feedback elicited in one-on-one interviews. We support this method of data collection but request that the FDA be more specific about how many interviews OPDP plans to conduct to compile this information, and what type of demographic diversity they will require when selecting people to be interviewed. A relatively small or homogeneous selection of individuals to interview one-on-one could result in unintentional bias in the survey, which in turn would have implications for the results of the estimated 1,100 completed surveys.

We urge you to consider our recommendations, which are intended to enhance the quality of the survey. We would be happy to help recruit patients for your survey or interviews.

 

REFERENCES

1. Sullivan, H. W., O’Donoghue, A. C., Lynch, M., Johnson, M., Davis, C., & Rupert, D. J. (2019). The Effect of Including Quantitative Information on Multiple Endpoints in Direct-to-Consumer Prescription Drug Television Advertisements. Medical decision making : an international journal of the Society for Medical Decision Making, 39(8), 975–985. https://doi.org/10.1177/0272989X19875946

2. Food & Drug Administration. (2015). The Impact of Direct-to-Consumer Advertising. https://www.fda.gov/drugs/information-consumers-and-patients-drugs/impact-direct-consumer-advertising 

NCHR Comments on USPSTF Draft Recommendation on Breast Cancer Screening

Breast Cancer, Legislation, Policy, Uncategorized,

June 6, 2023

We are pleased to have the opportunity to express our views regarding the U.S. Preventive Services Task Force Draft Recommendation Statement regarding breast cancer screening.

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. We do not accept funding from companies that make products that are the subject of our work, so we have no conflicts of interest.

While we support the task’s draft recommendation that women who are at average risk of breast cancer should undergo a screening every other year rather than annually, we are concerned that the task force’s recommendation of lowering the age of screening mammography from 50 years old to 40 years old is broadly applied to all women, rather than directed at groups most at risk. The guidelines are only supposed to be regarding women of average risk of breast cancer, and information is widely available to indicate some women are at higher risk because of genetic predispositions, smoking, obesity, family history, and other factors.  Dense breasts are also a risk factor, but unfortunately breast density also makes mammography less accurate[1] and tends to be especially high for women under the age of 50[2].

It is especially important to note that the most recent research, which may post-date the writing of these draft recommendations, had findings that suggested that Black females should start screening approximately 8 years earlier than White women, and that Hispanic and Asian and Pacific Islander females could start even later[3]. For that reason, we urge the USPSTF to consider whether the recommendation to start at age 40 should only apply to Black women and to other women who also have higher than average risk of breast cancer at a younger age, whereas starting at age 50 or even later is scientifically supported for other racial/ethnic groups that have been studied.

We agree with the USPSTF that there is not enough evidence to recommend screening mammography for women 75 years old or older.

We also agree that biennial mammogram screening has benefits that outweigh the risks for most women between the ages of 50-74 and for women at high risk between the ages of 40-50, there is currently insufficient evidence that using additional screening tools, such as using an MRI following a screening mammogram, is beneficial even for women with dense breasts, unless a diagnosis is needed when abnormalities are shown during the mammogram.

We understand that the USPSTF may be reluctant to suggest different screening schedules for Black women or for any specific group of women, but we urge the Task Force to focus on the scientific data. In this case, that includes different recommendations based on race and ethnicity data. Women are capable of understanding why the age to start mammography screening may be different for women with different risk factors. What is confusing is when some physician groups recommend annual mammograms for all women starting at age 40, even though the data do not support that recommendation. USPSTF should not compromise its standards to be more similar to those recommendations.

NCHR is grateful for the opportunity to comment on this USPSTF draft recommendation. The National Center for Health Research can be reached at info@center4research.org or (202) 223-4000.

 

REFERENCES

1) Kolb TM, Lichy J, Newhouse JH. Comparison of the performance of screening mammography, physical examination, and breast US and evaluation of factors that influence them: an analysis of 27,825 patient evaluations. Radiology. 2002 Oct;225(1):165-75. doi: 10.1148/radiol.2251011667. PMID: 12355001.

2) Barrette, Lori, Breast Density: What Women Should Know” University of Rochester Medical Center. 15 October 2015. <https://www.urmc.rochester.edu/news/publications/health-matters/breast-density-what-women-should-know>

3) Chen T, Kharazmi E, Fallah M. Race and Ethnicity–Adjusted Age Recommendation for Initiating Breast Cancer Screening. JAMA Netw Open. 2023;6(4):e238893. doi:10.1001/jamanetworkopen.2023.8893

Patient, Consumer, and Public Health Coalition Letter to FDA Commissioner Califf Regarding FDA Advisory Committee Meetings

Legislation, Policy

July 12, 2023

The Honorable Robert Califf, MD
Commissioner
Food and Drug Administration
10903 New Hampshire Ave.
Silver Springs, MD 20993

Dear Commissioner Califf,

As members of the Patient, Consumer, and Public Health Coalition, we appreciate your recent comments reaffirming your commitment to improving the format of Advisory Committees and look forward to working with you throughout these efforts. However, we also want to express our strong concerns when the Food and Drug Administration (FDA) Center Directors publicly undermine or privately overrule the recommendations of their own scientists’ and statisticians’ regarding applications for accelerated approval and full approval.

At our meeting with you on March 1, you expressed your view that some nonprofit leaders and academic researchers were inaccurately and unfairly assuming that FDA Advisory Committee members were more knowledgeable than the FDA scientific reviewers who had spent months reviewing the data and other information provided by sponsors. What we have seen for several years, particularly in recent months, is that the FDA Advisory Committee members often agree with scientific and statistical concerns and conclusions expressed in the FDA scientific memoranda provided to them to review, and it is the Center Directors or other officials that are overriding the views of FDA scientific reviewers.

Below we have summarized a few recent examples where the FDA decision conflicted with FDA scientists and statisticians summaries that were provided to FDA Advisory Committee members and the public.

FDA staff who presented the data at the FDA Advisory Committee meeting on May 12 regarding the accelerated approval application for Sarepta’s gene therapy Elevidys made it very clear that they did not feel remotely confident that the benefits outweighed the risks for boys ages 4-7. For example, they stated that the surrogate endpoint for the drug is not “reasonably likely to predict clinical benefit” in support of accelerated approval. They also stated that although the data appeared to be more promising for boys ages 4-5, the post-hoc analysis could not be trusted. However, in his remarks, Center Director Peter Marks told the Advisory Committee that the FDA should show flexibility by granting approval. We consider this flexibility especially problematic because FDA had previously granted accelerated approval to three other Sarepta drugs, none of which have completed their confirmatory trials. In fact, the confirmatory trial for Exondys 51, which was approved in 2016, were due in November 2020 but instead was not even started until July 2020.[1]

Despite Dr. Marks’ persuasive remarks at the Advisory Committee meeting, members only narrowly voted (8-6) in favor of the gene therapy, and even those who voted in favor expressed numerous concerns about the data. It has been reported that Dr. Marks overruled the recommendations of all FDA staff when he granted accelerated approval to Elevidys, consistent with what was clear for all to see at the Advisory Committee meeting.[2] Sarepta immediately announced that the treatment would cost $3.2 million per patient. Meanwhile, Sarepta is charging up to $1 million per patient per year for Exondys 51 – approximately four times the cost the company estimated in 2016. In fact, Sarepta has so far earned a total of $2.5 billion in sales from Exondys 51 and the two other Duchenne drugs granted accelerated approval.[3]

Unfortunately, the unilateral decision by CBER Director Peter Marks to overrule his own staff is troubling and harmful to the reputation of the FDA, as was the similar decision by CDER Director Janet Woodcock regarding Exondys 51 in 2016. These are just two of numerous examples where FDA Center Directors have gone against the recommendations of its own scientists and advisors to grant approval for a drug when the safety and effectiveness were not consistent with FDA requirements for approval. Two other recent examples include the controversial approval of Aduhelm (initially for all Alzheimer’s patients although it was only tested on patients with mild cognitive impairment) and Relyvrio for the treatment of patients with amyotrophic lateral sclerosis (ALS). These drugs will be marketed for years without confirmation of clinical benefit.

The June 28, 2023 Advisory Committee meeting regarding a drug for Fibrodysplasia ossificans progressive (FOP) is a somewhat different example. As was the case with Elevidys, the written memorandum by FDA staff expressed strong concerns about the scientific evidence: The primary end point was not met; the historical comparison sample was inappropriate; the data were manipulated post hoc in questionable ways; the nominal benefits were unreliable due to the wide confidence intervals; and there were increases in flare-ups – the very symptom that the drug was supposed to reduce. However, unlike the Elevidys meeting, the oral presentations by the FDA scientific and statistical staff were very obviously watered down versions of their written analyses. In fact, the main FDA presenter often seemed to be speaking on behalf of the sponsor, not the FDA. While still expressing concerns about whether the drug was safe and effective, the FDA speakers’ oral presentations contradicted the written FDA documents by stating that they were confident that the treatment probably had benefit and the risks of flare-ups were probably not so serious – an odd statement given that flare-ups were the outcome measure intended to be reduced by the treatment. Those statements were dramatically inconsistent with the written document summarizing the same analyses. This would have been worrisome but more justifiable for an accelerated approval, since the drug was intended to fulfill an unmet need for a terrible disease; however, the FDA meeting was considering full approval. FDA’s oral statements were so persuasive that several members of the Advisory Committee stated that the “FDA reassurances” convinced them that the benefits probably outweighed the risks, thus persuading them to vote in favor of the drug despite their strong reservations.

At an FDA Advisory Committee meeting in September 2022, FDA’s scientific summary of the confirmatory trials of PI3K inhibitor duvelisib (Copiktra) concluded that the risks outweigh the benefits for patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).  However, despite decreases in survival, the product retains its accelerated approval and FDA has not announced whether it intends to support those conclusions.

It is our understanding that FDA Advisory Committees are supposed to provide independent experts to review the FDA analyses, and not be unduly influenced by FDA staff or officials’ urging members how they should vote. Moreover, we agreed with your remarks on March 1 that FDA scientists and statisticians are the experts with the greatest knowledge of the data and the issues involved. It undermines the integrity of the FDA, the morale of FDA staff, and the public’s faith in FDA decisions when FDA officials grant an approval that contradicts its own scientists and statisticians. Equally important, overriding the scientific staff harms patients and contributes to a healthcare system that is financially unsustainable.

You have made it clear in numerous public statements that you are concerned about the format of Advisory Committee meetings, and we are as well. We urge you to speak out about the importance of FDA decisions supporting the FDA’s own scientific and statistical analyses. Please consider the following recommendations as you work to improve the format of the Advisory Committees:

  1. Provide training to FDA Advisory Committee members to help them understand the statistical analyses that are an essential part of all Advisory Committee meetings, and ensure they respect the importance of understanding and considering scientific evidence as part of their advisory role;
  2. Require that the FDA scientific and statistical staff who write the FDA memoranda for Advisory Committee meetings have the scientific freedom to express their own views, and that those views are accurately presented in FDA oral presentations at the meeting;
  3. Encourage Center Directors and other FDA officials attending Advisory Committee meetings to refrain from making comments that can be interpreted as encouraging committee members to vote a particular way; when FDA officials attend these meetings, their remarks should make it clear that FDA wants to hear their views and not to influence their votes.
  4. Remind Center Directors and other FDA officials that overruling the views of their own scientific and statistical staff undermines the public trust, and should be avoided, especially when the scientific staff are in consensus.

Sincerely,

American Medical Student Association Wisconsin

Breast Cancer Action

Doctors for America

Government Information Watch

Jacobs Institute of Women’s Health

Medical Device Problems

MISSD

Mothers Against Medical Error

MRSA Survivors Network

National Center for Health Research

National Women’s Health Network

Patient Safety Action Network

TMJ Association

USA Patient Network

Washington Advocates for Patient Safety

Woodymatters

 

 

1. ClinicalTrials.gov. A Study to Compare Safety and Efficacy of a High Dose of Eteplirsen in Participants With Duchenne Muscular Dystrophy (DMD) (MIS51ON). Available: https://clinicaltrials.gov/ct2/show/NCT03992430.

2. Becker, Z. (2023). In approving Sarepta’s DMD gene therapy, FDA’s Peter Marks overruled reviewer’s rejection. Fierce Pharma. Retrieved from https://www.fiercepharma.com/pharma/fda-biologics-director-peter-marks-spearheaded-sareptas-dmd-gene-therapy-approval-overruled. Accessed July. 5, 2023.

3. Langreth, R., Rutherford, F., Milton, I., & Campbell, M. (2023). Sarepta’s gene therapy gets FDA accelerated approval: Are fast-tracked drugs safe? Benefits Pro. https://www.benefitspro.com/2023/05/19/sareptas-gene-therapy-gets-accelerated-approval-are-fda-fast-tracked-drugs-safe/?slreturn=20230530114553. Accessed July. 5, 2023.

Meeting of Patient, Consumer, and Public Health Coalition with Commissioner Califf and Key FDA Officials

Legislation, Policy

March 1, 2023

Location: FDA White Oak Campus, Silver Spring, MD-Building 1, Great Room

FDA attendees: Robert Califf (Commissioner, virtual due to exposure to viruses), Peter Marks (Director, CBER, virtual), Owen Faris (OPEQ Principal Deputy Director, CDRH, virtual); In person: Julia Tierney (Chief of Staff, Office of the Commissioner), Jacqueline Corrigan-Curay, (Principal Deputy Director, CDER), Dayle Cristinizio (Director, Stakeholder Engagement, Office of External Affairs), Hilary Maston (Chief Medical Officer), Namandje Bumpus (Chief Scientist, AdCom responsibilities), Kaveeta Vasisht (Assoc Commissioner for Women’s Health), Jennifer Dooren (Director Communications and Public Engagement, Food Safety).

Coalition Attendees: In Person: Thomas Eagen (NCHR), Maria Gmitro (BISA), Denise Hyater-Lindenmuth (NWHN), Patricia Kelmar (U.S. PIRG), Suzanne Robotti (MedShadow), Kim Witczak (WoodyMatters), Diana Zuckerman (NCHR).  Virtual: Tahir Amin (I-MAK), Wendy Dolin (MISSD), Helen Haskell (MAME), Rex Johnson (WAPS), Katherine Leon (SCAD Alliance), Judy Norsigan (OBOS), Linda Radach (PSAN), Reshma Ramachandran (DFA), Brian Ronholm (Consumer Reports), Tess Schulman (Medical Device Problems), Robin Strongin (NCL), Dru West (USAPN), Sophia Phillips (on behalf of the Coalition).

On behalf of the Coalition members at the meeting, Dr. Diana Zuckerman offered our support to the Commissioner and the FDA, and thanked the Commissioner for his efforts to improve the Accelerated Approval program by requiring confirmatory trials be started prior to granting accelerated approval. Patricia Kelmar discussed members’ support for the FDA to regulate lab-developed tests to ensure their accuracy. Kim Witczak and Suzanne Robotti discussed possible improvements to the FDA Advisory Committee process, based on their perspectives as consumer representatives on two FDA Advisory Committees.  After the meeting was completed, Coalition members who were attending in person had informal discussions with several FDA officials.

Joint Letter from from Cancer Groups and Patient-Centered Nonprofits about VALID Act in Omnibus

Legislation, Policy

December 16, 2022

The Honorable Patty Murray
Chair
Senate Health, Education, Labor & Pensions Committee
Washington, DC 20510

The Honorable Richard Burr
Ranking Member
Senate Health, Education, Labor & Pensions Committee
Washington, DC 20510

The Honorable Frank Pallone
Chair
House Energy & Commerce Committee
Washington, DC 20515

The Honorable Cathy McMorris Rodgers
Ranking Member
House Energy & Commerce Committee
Washington, DC 20515

Dear Chair Murray, Ranking Member Burr, Chair Pallone, and Ranking Member Rodgers:

We are writing to express our strong support for your bipartisan support for the VALID Act earlier this year, and to urge you to include it in the Omnibus Spending bill with a few small improvements. Our concern is that women and men who are at high risk of breast cancer or other types of cancer are not currently able to have confidence that genetic tests used for screening and diagnosis are accurate. Our members were shocked to learn that the FDA only regulates diagnostic tests sold by companies, not those sold by laboratories. We have many examples of patients who have been terribly harmed when lab-developed diagnostic tests that were widely sold have been dangerously inaccurate. There are currently approximately 100,000 different lab developed tests that would be grandfathered under the current bill language, and none of them would be required to submit evidence now or in the future to prove that their tests are accurate. Even the highest risk lab developed tests that are currently being sold could continue to be sold without any restrictions, and it is unclear if serious adverse events caused by inaccurate tests would be reported to the FDA. That is unacceptable to us as patient-centered organizations.

Your constituents deserve better. In addition to the extensive grandfathering, the bill would categorize lab-developed tests as low, moderate, or high-risk. Low-risk would be essentially unregulated, moderate risk would  require some evidence but not be tested for accuracy (similar to the 510(k) review process). As you know, the 510(k) pathway is used to review approximately 95% of all medical devices, including most implanted devices, and it has been strongly criticized by physicians, patients, and public health experts because many of those devices are high risk, not moderate risk as the FDA claims.

As described in the current VALID provisions in the bill, only the highest risk devices would be required to provide clear evidence of accuracy, and the definition of high risk is unclear and based on the FDA’s track record is likely to exclude many tests that could cause irreparable harm, such as genetic tests that are used to inform people that they are at very high risk of breast cancer, ovarian cancer, stomach cancer, and other very serious diseases. Since many patients who are told that they tested positive for these genetic mutations have those important bodily organs surgically removed, those genetic tests should be considered high-risk. It would be equally tragic for a person to have an organ unnecessarily removed due to an inaccurate positive test result, or for a person to be incorrectly told they did not have a life-threatening genetic mutation, due to a false test negative result. Although we are focusing on breast cancer in this letter, it is well-known that most prenatal genetic testing is inaccurate, thus resulting in terminating wanted pregnancies because they were erroneously told their baby had a fatal birth defect. For that reason we strongly urge you to include genetic testing in the definition of “high risk” tests in the bill, and not allow grandfathering of high risk tests.

In addition to these shortcomings, we are concerned that academic medical centers are lobbying to be excluded from FDA regulation. While academic medical centers have an important role to play in U.S. healthcare, their tests are not monitored by the FDA, CMS, or any other independent entity to ensure they are accurate.  As a result, there are clear examples of tests that were dangerously inaccurate.  Any exemption for academic medical centers’ lab-developed tests should be extremely narrow, to target tests used for individuals, not for large numbers of patients.  High-risk tests should always be regulated.

In conclusion, we strongly recommend including an improved version of the VALID Act, as described above, in the Omnibus bill, in order to better protect patients and consumers from inaccurate and unreliable lab-developed tests.

Sincerely,

Breast Implant Safety Alliance

Cancer Prevention and Treatment Fund

National Women’s Health Network

Not Putting on a Shirt

Our Bodies Ourselves

Patient Safety Action Network

USA Patient Network

Washington Advocates for Patient Safety

WoodyMatters

 

Cc: Members of Senate Health, Education, Labor, and Pension Committee and Members of Energy & Commerce Health Subcommittee

Comment of the National Center for Health Research Submitted to the EPA on the Designation of PFOA and PFOS as CERCLA Hazardous Substances, October 6, 2022

Legislation, Policy

October 6, 2022

The National Center for Health Research appreciates the opportunity to provide comments on the designation of PFOA and PFOS as CERCLA hazardous substances. We are a public health think tank that conducts research, scrutinizes research conducted by others, and determines how research findings can be used to improve health policies and explains what is known and not known about the risks and benefits of specific products, programs, and policies.

For several years, we have been actively engaged in the study of the impact of PFOA, PFOS, and other PFAS chemicals on human health. There is clear evidence that these chemicals can disrupt the endocrine system in humans even at low levels.  Exposure can exacerbate such common conditions as obesity, early puberty, attention disorders, and eventually cause cancer.  We are therefore writing in strong support of the designation of PFOA and PFOS as CERCLA hazardous substances. This is an important first step because it holds companies accountable for these toxic substances, which in turn will improve public health.

Unfortunately, detailed information is lacking on most of the thousands of compounds that comprise PFAS.  Since it is unlikely that EPA can compile comprehensive toxicity data on all members of this class of chemicals, EPA should make it an urgent priority to work with independent researchers and other federal agencies to develop a common definition of PFAS, and ensure that researchers and regulatory agencies assess and restrict these chemicals as a class. PFAS classes should be determined based on exposure data, chemicals that are located or utilized together, and other parameters such as structure. Known hazards in well-studied compounds should be assumed to extrapolate to similar compounds that lack good data, until research is conducted to fill those data gaps.

In conclusion, the National Center for Health Research agrees that the designation of PFOA and PFOS as CERCLA hazardous substances is consistent with the clear evidence that these chemicals disrupt the endocrine system, accumulate in the environment and in the human body, and can cause serious health problems for humans and other animals.  Since there are thousands of other chemicals with similar structures that are not yet regulated, despite the assumption that they can cause similar harm, we strongly urge the EPA to regulate PFAS as a class of chemicals for the protection of public health and our environment.

For additional information about our work in this area, contact info@center4research.org.

Joint Letter to Support FDA Proposed Rule Reducing Nicotine Levels in Cigarettes

Legislation, Policy, ,

September 12, 2022

Dr. Robert Califf
Commissioner
U.S. Food and Drug Administration
10903 New Hampshire Avenue
Silver Spring, MD 20993

Re: Nicotine Standard

Dear Dr. Califf:

The undersigned public health, medical and professional organizations write in strong support of your recent announcement that FDA will issue a proposed rule to reduce the nicotine level in cigarettes to non-addictive or minimally addictive levels. Such a standard would generate massive public health benefits, preventing millions of young people from smoking and dramatically reducing the number of people who die from tobacco-caused diseases. We urge you to move forward with this proposal as quickly as possible.

Despite great progress in curbing smoking prevalence in recent years, tobacco use – primarily smoking – remains the leading cause of preventable death and disease in the United States, killing more than 480,000 Americans every year.1 Sixteen million Americans are currently living with a tobacco-caused disease.2 Over 30 million Americans currently smoke, and every day over 1,600 kids try their first cigarette.3 Approximately half of people who smoke will die prematurely as a result of their addiction, losing at least a decade of life on average compared to those who do not smoke.4

We applaud the Administration for taking action to reduce tobacco use as part of its Cancer Moonshot initiative.5 Cigarette smoking causes about 30 percent of all cancer deaths in the U.S.6 Reductions in tobacco use have already had an impact on cancer rates. According to CDC, 60 percent of the decrease in cancer death rates among men and 40 percent of the decrease among women from their peak in 1990 to 1991 until 2014 were due to declines in tobacco-related cancer deaths.7 More progress can be made and reducing nicotine levels will have a profound impact.

Nicotine is the primary addictive agent in cigarettes and other tobacco products. According to the U.S. Surgeon General, “the addiction caused by the nicotine in tobacco smoke is critical in the transition of smokers from experimentation to sustained smoking and, subsequently, in the maintenance of smoking for the majority of smokers who want to quit.”8 Thus, reducing the nicotine content in cigarettes to non-addictive or minimally addictive levels will prevent experimentation by the young from becoming a lifetime of addiction and tobacco-caused disease. It also will reduce the level of nicotine dependence in adults who smoke, making it easier for them to quit.

Current evidence establishes the potentially historic lifesaving impact of reducing nicotine content in cigarettes to non-addictive or minimally addictive levels. As you know, FDA estimated in 2018 that approximately 5 million additional adults who smoke could quit smoking within one year of implementation and, by the year 2100, more than 33 million people – mostly youth and young adults – would have avoided becoming regular smokers. Smoking rates could drop to as low as 1.4 percent, resulting in more than 8 million fewer tobacco-caused deaths through the end of the century.9 The dimensions of this public health benefit make timely implementation of this policy a moral imperative.

Reducing nicotine levels in cigarettes to achieve these enormous public health gains is technologically feasible. As FDA noted in its earlier Advance Notice of Proposed Rulemaking (ANPRM), there are a wide range of available technologies to reduce nicotine in cigarettes, including “through tobacco blending and cross-breeding plants, genetic engineering, and chemical extraction.”10 Indeed, the tobacco industry’s own documents show that the industry has a long history of manipulating nicotine levels in cigarettes to make them more addictive. As U.S. District Court Judge Gladys Kessler determined in her landmark opinion finding that the major cigarette companies had violated the federal anti-racketeering statute, “Defendants have designed their cigarettes to precisely control nicotine delivery levels and provide doses of nicotine sufficient to create and sustain addiction.”11 Surely the companies cannot now credibly maintain that they are unable to reduce nicotine levels to no longer sustain addiction. In addition, FDA has noted that recent scientific studies do not support concerns that nicotine reduction would cause people who smoke to compensate by increasing the number of cigarettes smoked or inhaling more deeply to increase nicotine intake. Studies of very low nicotine cigarettes have not found evidence of compensatory smoking but have found demonstrable reductions in cigarettes smoked per day and in exposure to harmful smoking constituents.12

To realize the full potential public health benefits of a nicotine product standard, FDA must extend that standard beyond cigarettes, to other combustible tobacco products. Exempting other combustible products would invite tobacco manufacturers to market existing, or develop new, non-cigarette substitutes, like the small, flavored cigars the industry introduced after flavored cigarettes (except menthol) were removed from the market. It also would make the exempted products a potential vehicle for youth initiation. Thus, we urge FDA to make any nicotine reduction product standard applicable to other combustible tobacco products.

Reducing nicotine in cigarettes and other combusted tobacco products will complement FDA’s proposed rules to prohibit menthol cigarettes and flavored cigars. By addressing flavors and nicotine levels, FDA will be able to target both what attracts youth to these products and what addicts them. FDA should continue its work to promptly finalize and implement the menthol cigarette and flavored cigar proposed rules. Moreover, FDA should continue to address high rates of e-cigarette use by youth by promptly completing statutorily required premarket reviews and removing from the market those products that are not “appropriate for the protection of the public health.”

Reducing the nicotine content in cigarettes and other combustible tobacco products will dramatically reduce addiction, disease, and premature death from tobacco. We applaud FDA for setting forth a bold plan to protect kids and public health and urge the agency to act quickly to complete the rulemaking process. Every day that passes means more kids moving from experimentation to addiction and more adults who want to quit, and try to quit, but remain addicted to a lethal product.

Respectfully submitted,

AASA, The School Superintendents Association
Academy of General Dentistry
Action on Smoking and Health
Allergy & Asthma Network
Alpha-1 Foundation
American Academy of Family Physicians
American Academy of Oral and Maxillofacial Pathology
American Association for Cancer Research
American Association for Dental, Oral, and Craniofacial Research
American Association for Respiratory Care
American Cancer Society Cancer Action Network
American College of Cardiology
American College of Physicians
American Dental Association
American Heart Association
American Public Health Association
American Society of Addiction Medicine
Americans for Nonsmokers’ Rights
Association for Clinical Oncology
Association for the Treatment of Tobacco Use & Dependence
Association of Black Cardiologists
Association of State and Territorial Health Officials
Asthma and Allergy Foundation of America
Campaign for Tobacco-Free Kids
Cancer Prevention and Treatment Fund
Catholic Health Association of the United States
Center For Black Equity
Children’s Health Fund
Commissioned Officers Association of the USPHS
Common Sense Media
Community Anti-Drug Coalitions of America (CADCA)
COPD Foundation
Counter Tools
Dana-Farber Cancer Institute
Emphysema Foundation of America
Family, Career and Community Leaders of America (FCCLA)
First Focus on Children
GLMA: Health Professionals Advancing
LGBTQ+ Equality
GO2 Foundation for Lung Cancer
HealthHIV
International Association for the Study of Lung Cancer
Kaiser Permanente
March of Dimes
National Alliance to Advance Adolescent Health
National Association of Hispanic Nurses
National Association of Pediatric Nurse Practitioners
National Association of School Nurses
National Association of Secondary School Principals
National Black Church Initiative
National Black Nurses Association
National Education Association
National Hispanic Medical Association
National LGBT Cancer Network
National Medical Association
National Native Network
National Network of Public Health Institutes
National Tongan American Society
North American Quitline Consortium
Oncology Nursing Society
Parents Against Vaping e-cigarettes (PAVe)
Preventing Tobacco Addiction
Foundation/Tobacco 21
Preventive Cardiovascular Nurses Association
Respiratory Health Association
SADD
Society for Cardiovascular Angiography & Interventions
The Center for Black Health and Equity
The Society for State Leaders of Health
and Physical Education
The Society of Thoracic Surgeons
Trust for America’s Health
Truth Initiative
US COPD Coalition

CC: Dr. Brian King, Director of the Center for Tobacco Products

1. HHS, The Health Consequences of Smoking – 50 Years of Progress: A Report of the Surgeon General, 2014 (2014 SG Report).
2. Id.
3. CDC, “Tobacco Product Use Among Adults—United States, 2020,” MMWR Morb Mortal Wkly Rep
2022;71:397–405, March 18, 2022, https://www.cdc.gov/mmwr/volumes/71/wr/mm7111a1.htms_cid=mm7111a1_w. Substance Abuse and Mental Health Services Administration (SAMHSA), HHS, Results from the 2019 National Survey on Drug Use and Health, NSDUH: Detailed Tables, Table 4.9A https://www.samhsa.gov/data/report/2019-nsduh-detailed-tables
4. 2014 SG Report
5. The White House, “President Biden Reignites Cancer Moonshot to End Cancer as We Know It,” Fact Sheet. February, 2, 2022, https://www.whitehouse.gov/briefing-room/statements-releases/2022/02/02/fact-sheet-president-
biden-reignites-cancer-moonshot-to-end-cancer-as-we-know-it/
6. American Cancer Society. Cancer Facts & Figures 2022. Atlanta: American Cancer Society, 2022.
https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2022.html
7. CDC, “Vital Signs: Disparities in Tobacco-Related Cancer Incidence and Mortality—United States, 2004-2013,” MMWR 65(44): 1212-1218, https://www.cdc.gov/mmwr/volumes/65/wr/pdfs/mm6544a3.pdf/.
8. 2014 SG Report.
9. Apelberg, BJ, et al., “Potential Public Health Effects of Reducing Nicotine Levels in Cigarettes in the United States,” New England Journal of Medicine, published online March 15, 2018. See also, “Tobacco Product Standard for Nicotine Level of Combusted Cigarettes,” Advance Notice of Proposed Rulemaking, 83 Fed. Reg. 11818, 11820 (March 16, 2018)(ANPRM)
10. ANPRM, at 11820.
11. U.S. v. Philip Morris, Inc., 449 F.Supp. 2d, 1, 309 (D.D.C. 2006), aff’d in relevant part. 566 F.3d 1095 (D.C. Cir.2009).
12. ANPRM, at 11820.

Draft Senate Contact Letter for Patients Supporting User Fee legislation With Policy Riders

Legislation, Policy

[Date]

Dear [Name of Senator],

I am writing on behalf of myself as a cancer [patient/advocate] and constituent of the state of [add State] to convey my strong opposition to efforts to strip user fee legislation of important public health protections in favor of a “clean” user fee bill. I urge that as you work to reconcile these bills, you address urgent public health challenges by maintaining critical protections in the FDA Safety and Landmark Advancements Act (FDASLA), S. 4348.

This legislation must include provisions that will help ensure the safety and efficacy of cancer drugs, as well as accuracy and reliability for cancer-related diagnostic tests. Accelerated approval reform is necessary to protect patients such as [myself/ my relative/other] from harmful and possibly ineffective treatments. Reform to diagnostic tests will provide the FDA with the authority and resources necessary to ensure that the highest-risk diagnostic tests are valid and reliable. Increasing numbers of patients make life-altering decisions based on diagnostic tests, which can be used to predict cancer or fetal abnormalities.

We urge you not to forgo this key opportunity to advance long-awaited solutions for the American public. While some provisions could be strengthened still further from the Senate version, we express our continued support for the meaningful reforms contained in the bill, and hope that Congressional and committee leadership remain committed to negotiating these protections as you advance this important legislation.

Thank you,

[Name]

[Affiliation if applicable]

NCHR Comments on the MDUFA V Commitment Letter

Legislation, Uncategorized, ,

April 21, 2022

The National Center for Health Research (NCHR) appreciates the opportunity to provide public comments on the Medical Device User Fee Amendments (MDUFA) V Commitment letter, and to express our substantial concerns with the overall process as well as the shortcomings of the Commitment letter.

NCHR is a nonprofit think tank that conducts, analyzes, and scrutinizes research on a range of health issues and health policies, with particular focus on ensuring that treatments are safe and effective for patients and consumers. We do not accept funding from companies that make products that are the subject of our work, so we have no conflicts of interest.

The negotiations between the Food and Drug Administration (FDA) and medical device industry are unlike regulatory processes at other federal agencies. The typical process is more transparent and includes meaningful stakeholder engagement and feedback from the public. The fact that the very industries being regulated by the FDA meet behind closed doors with FDA staff to negotiate a Commitment Letter, with no members of the public allowed to be in the room or have access to a transcript or recording, raises important questions about why industry has more say in FDA policies and practices than other Stakeholders. We previously pointed out the lack of transparency and the lack of meeting minutes, which we were told would be publicly available – but weren’t.

This proposed Commitment letter, although late, has already been delivered to Members of Congress. The House Energy & Commerce Subcommittee on Health held a hearing on March 30, 2022, on the contents of the proposed Commitment Letter. It seems disingenuous to request public feedback, at this week’s meeting or in writing, at this late point in the process.

In addition to the lack of transparency in the process and lack of public representation in negotiations between FDA and the medical device industry, the Commitment Letter fails to include any performance measures specifically linked to patient safety. Given the lack of safety or effectiveness data prior to clearance or approval of more than 95% of medical devices, post-market surveillance is crucially important. And yet, the Commitment Letter provides no requirement for financial support for post-market monitoring of studies or MAUDE reports, putting patients at risk for years to come.

Despite our lack of confidence in the FDA’s negotiated agreement with industry, below are our specific recommendations for your consideration as you finalize the MDUFA V Commitment Letter:

  1. Include performance measures tied to device safety, such as total time to recall a device following adverse event reporting.
  2. Direct any additional funds earned by FDA for meeting premarket performance goals to post-market surveillance activities.
  3. The total product life cycle advisory program (TAP) should include post-market activities to truly capture the full life cycle. This is becoming even more important as devices become more complex and technology rapidly changes. User fees should be used to support technology systems to monitor devices. Based on the description in the proposed Commitment Letter, TAP would focus on early communication with industry to troubleshoot potential issues with applications, but not to monitor the devices once they are on the market.
  4. Diversity and accessibility performance measures should be included in the proposed Commitment Letter.
    1. Industry could be provided a discount on fees if certain diversity performance goals are met in a PMA application.
    2. Industry should be required to include a detailed plan on potential device recalls. The plan should include how information will be shared with patients and what steps will be taken to ensure the information is presented in a timely manner and accessible formats.

When Congress required that stakeholders have the opportunity to participate in the MDUFA V reauthorization process, they intended that our participation would be meaningful. This is the final opportunity for the FDA to fulfill that obligation in MDUFA V.