Letter of Opposition to Trickett Wendler Right to Try Act of 2017 (S. 204)

clip_image002February 24, 2017
United States Senate
Washington, DC 20510

Dear Senator:

As members of the Patient, Consumer, and Public Health Coalition, we are writing to thank you for not co-sponsoring the Trickett Wendler Right to Try Act of 2017 (S. 204), introduced by Sen. Ron Johnson (R-WI).  We urge you to strongly oppose this measure.

This bill purports to help dying patients gain access to experimental treatments that can save their lives.  However, patients already have this access through the FDA’s Expanded Access Program, which gives patients access to experimental drugs if their doctor believes it is appropriate and the company making the drug agrees to provide it for that use.  The bill instead does something much more dangerous: It would remove the FDA’s role in protecting many millions of patients from unsafe or ineffective treatment options – patients who already have safe and effective treatment options.

While we all greatly sympathize with the need for terminally ill patients to receive the best medical treatments as quickly as possible, the right-to-try approach of this legislation would:

➢    Hinder patients’ ability to obtain the experimental drugs that are more likely to help them.

➢    Enable companies to charge for experimental drugs, instead of providing them for free in clinical trials.

➢    Reduce or eliminate the incentive of pharmaceutical companies to do scientific studies to prove that their medications are safe or effective, and for whom.  Why would companies agree to spend time and money researching their product when the company can spend that money on marketing it instead?

➢    Due to the lack of incentive to conduct clinical trials, could make it impossible to scientifically prove if a medication will make the patient feel better or live longer, and what dosage the patient should take.

➢    For the same reason as above, could make it impossible to scientifically prove if the side effects are so debilitating or dangerous that they outweigh the risks for most patients.

This scenario would take us back to the early twentieth century, when “snake oil salesman” peddled untested home remedies and “cures” to patients who had no access to information about whether the product would help or harm them.  Indeed, tragedies arising from those “right to try” laissez faire and harmful medical policies were the very reason that the FDA was created.

While this Senate and House legislation calls for access to experimental drugs which have completed Phase 1 clinical trials, and remain under investigation in a clinical trial approved by FDA, Phase 1 trials are conducted with only small groups of healthy volunteers or patients to determine safe dosage range and identify relatively frequent, short-term side effects.  These very preliminary trials are only the beginning of safety testing, and do not test for effectiveness.

As noted above, the FDA already has a program in place to expedite access to experimental and unapproved drugs for which there is some evidence of safety and efficacy and some knowledge about the appropriate dosage.  The FDA Expanded Access Program routinely utilizes what the agency terms “compassionate use” for patients when doctors request such access.  As would also be the case under all Right-to-Try laws, access to the treatment is determined by the company; if the company doesn’t want to provide the experimental treatment to the individual patient, it does not have to do so.  Under current law, when the company agrees to provide the drug to the patient, the FDA quickly agrees to allow the patient access more than 95% of the time.  Moreover, in urgent circumstances, the FDA had made such a decision within 1 or 2 days.

Currently, the most difficult part of the process is for doctors to obtain permission from the company.  The FDA is working to facilitate access by ensuring that companies make it easier for doctors and patients to quickly identify the contact person or persons at each company who is in charge of the Expanded Access Program.  The drug companies are also asked to make their policies regarding access to specific experimental drugs easily available to the public.

It is important to note that insurance companies generally do not pay for experimental treatments.  This is not a problem in clinical trials or under the FDA’s Expanded Access Program, because in those cases, treatment is almost always free.  However, there is reason to be concerned that pharmaceutical officials will be unwilling to make experimental treatments available for free if they are more frequently requested under the proposed Right to Try Act.

No Evidence that Lives Will Be Saved

In addition to other problems with the legislation, it does not clearly define “terminally ill” patient, or who makes that determination.  How many patients with cancer or heart disease would be considered terminally ill, since those serious illnesses can cause death?  It is not always possible to predict how long a seriously ill person will live, and patients could be easily manipulated by scam artists and others who are motivated by financial gain to convince patients to “try” the “latest” experimental treatment.  Such problems have long been documented regarding unproven treatments sold at outrageously high prices in Mexico, where patients have been irreparably harmed by such treatments.

Bioethics experts and many physicians also point to the following problems with the law:

✓    Desperate patients will be vulnerable to false or misleading promises about likely benefits and failed to be warned about the risks, which may include dying earlier and more painfully than they would without the experimental treatment.

✓    Despite patients’ hopes, there is no evidence that access to experimental treatments through humanitarian exemptions helps more patients than it harms.

✓    There is no evidence that various state right–to-try laws have saved lives or improved patient outcomes.

✓    A survey conducted by Modern Healthcare in late 2015 found no evidence of patients receiving an experimental therapy as a result of state right-to-try laws, despite the fact that more than 20 states already had such laws in place.

✓    If a federal Right to Try Act were to become law, even small companies that make prescription drugs would need to develop complex policies to make such treatments available.

We urge you to strongly oppose S. 204 because it would undermine the successful program already in place to enable patients to have access to experimental drugs for free or at cost.  The proposed law would potentially harm many patients and family members, including seriously ill patients who could be harmed by scam artists in a treatment environment with no checks and balances. This legislation could open the floodgates to undermine the scientific requirements that made FDA approval the gold standard for the world.

Sincerely,

National Center for Health Research
American Medical Women’s Association (AMWA)
Association for Medical Ethics (AME)
Breast Cancer Action (BCA)
Breast Cancer Consortium
Breast Implant Victim Advocacy
Center for Medical Consumers
DES Action
Jacob’s Institute of Women’s Health
MedShadow
MISSD
Mothers Against Medical Error (MAME)
MRSA Survivors Network
National Consumers League (NCL)
National Physicians Alliance (NPA)
National Women’s Health Network (NWHN)
Our Bodies Ourselves
Quinolone Vigilance Foundation
TMJ Association
Washington Advocates for Patient Safety
WoodyMatters
For more information, please contact Jack Mitchell at jm@center4research.org.

Coalition Letter Protesting 21st Century Cures

November 29, 2016

The Honorable ________
United States House of Representatives
Washington, DC 20515

Dear Senator/Congressman ____:

The undersigned nonprofit organizations represent members of the Patient, Consumer and Public Health Coalition, which includes more than 6 million healthcare providers, public health experts, and consumer and patient advocates.  We are writing to urgently express our strong opposition to the newly revised 21st Century Cures Act, both in terms of the process of trying to pass a bill without adequate time for public debate, and for specific provisions in the bill that would harm patient safety.  Passing a complicated health bill in the rush of a lame-duck session is always problematic.  Passing a 996-page bill that was negotiated behind closed doors and includes provisions that were never voted on before represents the kind of legislative sausage that Congress should reject.

While the bill includes some positive measures, the most important ones – funding for the National Institutes of Health (NIH) and the Opioid bill that previously passed – are not guaranteed in this legislation.  Unlike the earlier version of the 21st Century Cures Act that was passed in 2015, the funding is not mandated in the new version.  In exchange for the hope of additional funding, the bill contains dangerous measures that would lower safety and approval standards for drugs and medical devices at the Food and Drug Administration (FDA).  This would put all patients and consumers at risk.

For example, the bill would allow antibiotics to be approved based on minimal evidence of safety and effectiveness through a “limited population” approval pathway.  The bill would not require that the antibiotics be studied on the target population that the new drugs would be approved for.  In other words, it is possible that the antibiotics would not meet the urgent need that they are intended for.  Unfortunately, these antibiotics could then be widely advertised and used by patients who are not likely to benefit, and could be seriously harmed by them.  In the long run, that would contribute to antibiotic resistance.  While the Senate version had several restrictions designed to help protect patients, the 21st Century Cures version released this past weekend does not.

The MEDTECH section of the bill would deregulate electronic medical records and decision support software.  A study by the National Center of Health Research (NCHR) found that these types of health IT devices can cause life-threatening problems when they miscalculate incorrect drug dosages for chemotherapy drugs and other treatments.  The Breakthrough Devices (Sec. 3051) encourages shorter and smaller clinical trials for medical devices. These smaller studies make it impossible to include sufficient numbers of women, men, seniors, and racial and ethnic minorities.  Moreover, a recent study of high-risk medical devices found that the median number of participants is currently only 65 patients, which is already too small a cohort to adequately evaluate safety and effectiveness for both men and women, let alone for elderly men and women compared to young adults, or for minority populations.

The bill would also drastically lower standards by allowing companies to provide FDA with summaries of their data, instead of the data itself, as now required, when they want to sell drugs for new indications (treatments).  It also encourages the FDA to make approval decisions based on “real world evidence” that is not necessarily scientifically sound.  The FDA currently reviews and scrutinizes scientific data provided by companies, which is necessary to make sure the benefits outweigh the risks for any approved indication.  Providing summaries would also reduce information about the possible risks to particular demographic groups, such as women or patients over 65.

The Accelerated Approval for Regenerative Advanced Therapies (Sec. 3033), creates an expedited review pathway for ‘regenerative medicine.’  This section has been promoted by extensive campaign contributions, was not in any previous version of the Cures legislation, and should not be rushed through without adequate discussion and debate.

The bill also allows off-label promotion of medical products under certain circumstances, which reduces the incentive for companies to conduct scientific research to prove that their products are safe and effective for new indications.

By lowering standards for approval of drugs and devices, and in some cases eliminating them, the bill would increase the cost of healthcare and pharmaceuticals at a time when such costs have become a grave threat to affordability of health insurance and to the survival of Medicare.  The implications for patients’ health and the affordability of medical care can’t be overstated.  Researchers at the best medical schools in the country already have shown that many ineffective and unsafe drugs have already been approved by FDA on the basis of the kind of preliminary data encouraged by 21st Century Cures.

This situation would worsen under the bill.  For example, the National Center for Health Research assessed the cost of new, ineffective cancer drugs and found that they cost the same or more as cancer drugs that are proven to work.  In addition, the bill would continue the existing pediatric priority review voucher program, even though a recent GAO review of the program concluded that the program has questionable benefit.  This increases the cost of medications and undermines FDA’s ability to set its work priorities based on public health needs.

The extensive and expensive lobbying efforts in favor of 21st Century Cures have been designed to make every aspect of the bill seem bipartisan and non-controversial.  If that were true, however, the bill would not have been negotiated behind closed doors and released during the Thanksgiving holiday weekend.  That is why dozens of patient, consumer, physician, labor, and public interest groups, as well as former Members of Congress, have asked the Congress to delay consideration of the bill.

Thank you for your consideration of our views on this legislation.  We must ensure that patients can trust their drugs and medical devices to improve their health rather than harm it.

Sincerely,

National Center for Health Research
American Medical Student Association
American Medical Women’s Association
Annie Appleseed
Association for Medical Ethics (AME)
Advocating Safety in Healthcare E-Sisters (ASHES)
Breast Cancer Action
Center for Medical Consumers
Connecticut Center for Patient Safety
ISMP
Jacobs Institute
Mothers Against Medical Errors
MISSD
MRSA Survivors Network
National Physicians Alliance
National Women’s Health Network
Our Bodies, Ourselves
Quinolone Vigilance Foundation
TMJ Association
Treatment Action Group
Union of Concerned Scientists
Washington Advocates for Patient Safety (WAPS)
WomenHeart: The National Coalition for Women with Heart Disease
WoodyMatters

 

For more information, please contact Jack Mitchell at jm@center4research.org.

Coalition Comment on Conflicts of Interest

Untitled

Comments of members of the Patient, Consumer, and Public Health Coalition on
“Procedures for Evaluating Appearance Issues and Granting Authorizations for Participation in Food and Drug Administration Advisory Committees; Draft Guidance for the Public, Food and Drug Administration Advisory Committee Members, and Food and Drug Administration Staff; Availability; Extension of Comment Period”

Docket No. FDA-2016-D-1399

As members of the Patient, Consumer, and Public Health Coalition we are writing to respond to the FDA’s draft guidance for comments on appearances of conflicts of interest. In our view, there are troublesome inconsistencies in the way that the FDA considers financial conflicts of interest and how they consider appearances of conflicts of interest. Moreover, there are also troubling inconsistencies in how the FDA perceives such appearances for public health and consumer advocates and how they are considered for clinicians.

FDA defines financial conflicts of interest as financial ties during the previous 12 months, so even extensive financial ties in the recent past – or even 12 months plus one day earlier — do not require a waiver. And yet, FDA’s determinations of appearances of conflicts of interest seem to last for years, even decades, if the latter involves a person who previously expressed concerns about a company or a product. On the other hand, Advisory Committee members who previously favored a product are often considered to have important knowledge and experience, rather than having an appearance of a conflict of interest.

The FDA advisory committee that met in 2011 to discuss whether Yaz oral contraceptives are too risky to stay on the market is a perfect example of the one-sided way FDA considers these appearances of conflicts of interest. Dr. Sidney Wolfe was not allowed to vote because he had previously expressed concerns about Bayer’s Yaz. On the other hand, Advisory Committee members with extensive financial ties to Bayer that were more than a year prior voted in support of Yaz (and Yasmin, Beyaz, and other contraceptives made with the hormone drosperinone). This shifted the vote to keep these pills on the market. In other words, many conflicted advisory committee members weren’t counted as “conflicted” because their financial ties were more than a year old. In addition, doctors who had previously prescribed Yaz and other contraceptives made with drosperinone, or who had stopped prescribing it, were allowed to be voting members of the Advisory Committee. In our view, those treatment decisions reflect potential sources of bias or knowledge (whichever interpretation that you prefer) that predates the meeting, that was no less than bias or knowledge that Dr. Wolfe might have had prior to the meeting.

Similarly, at the 2016 Advisory Committee meeting on Chantix, consumer representative Kim Witczak was removed from committee because the FDA identified the appearance of conflicts of interest based on incidents that were well over a year old – in fact, one of the two conflicts FDA cited was over 10 years old. The one that was just over a year old consisted of her speaking during a public comment period during the previous FDA Advisory Committee meeting on the same topic. And yet, 11 of the 27 members of the Committee had previously voted for or against warnings about Chantix at that same meeting. Why was Ms. Witczak’s 3 minutes of public comment disqualifying as a conflict of interest, but comments and votes from previous Committee members were not considered disqualifying? Why was it assumed that Committee members would be open-minded enough to consider new evidence, but Ms. Witczak was not considered open-minded enough to do the same?

For committee meetings reconsidering safety issues for popular products such as Vioxx, Avandia, Yaz, osteoporosis drugs, surgical mesh, hip joints, and breast implants, advisory members who have frequently prescribed or implanted the products being reviewed are not considered biased and also do not need to have waivers. Isn’t the fact that the doctors prescribed a product an indication of an appearance of a conflict of interest in favor of the product? These potentially more knowledgeable but possibly less objective members influence how others vote at least as much if not more than a public health expert or researcher who has previously spoken about or written about the risks or benefits of a medical product.

The National Center for Health Research did a study of FDA Advisory Committee meetings and members of this coalition have attended dozens of them. It is clear from these meetings that many Advisory Committee members are clinicians who want more treatments to be available, making comments such as “if this drug can help one patient, we should get it on the market.” FDA’s responsibility is to make decisions based on scientific evidence that patients are more likely to be helped than harmed by a new medication or medical device. They are asked to provide their perspectives based on objective analysis of the information provided, not on speculation or wishful thinking about whether a drug might “help at least one patient.” Those hopes can appear to be a conflict of interest.

Whether FDA Advisory Committee members have financial conflicts of interest or other types of bias, the standards in terms of the numbers of years should be identical. One year is too short, and 10 years is too long. In industry and academia, 3-5 years is generally considered to be an appropriate amount of time to consider such conflicts. Equally important, bias in favor or opposed to a product should be equally disqualifying; either the Advisory Committee members are able to have an open mind to consider new information, or they aren’t. Disqualification on the basis of an “appearance” of a conflict of interest should not depend on whether the sponsor is opposed to having that person on the Committee.
Thank you for the opportunity to share our concerns regarding the Draft Guidance.

Sincerely,

National Center for Health Research
Association for Medical Ethics (AME)
Breast Cancer Action
Center for Medical Consumers
Connecticut Center for Patient Safety
Mothers Against Medical Error (MAME)
MRSA Survivors Network
National Women’s Health Network
Our Bodies Ourselves
Quinolone Vigilance Foundation
Washington Advocates for Patient Safety (WAPS)
WoodyMatters

For more information, please contact Jack Mitchell at jm@center4research.org.

Testimony to FDA panel on consideration of off-label promotion of medical devices

November 10, 2016

Thank you for the opportunity to speak today.  My name is Jack Mitchell, and I’m the director of government relations for the non-profit National Center for Health Research, which performs public health research and conducts patient advocacy.  This morning I’m speaking on behalf of the Patient, Consumer and Public Health Coalition, to which NCHR belongs and helps to coordinate.

The Coalition includes both large and small nonprofit organizations across the country that are united to ensure that medical treatments are safe and effective, and to enhance the scientific and public health focus of the FDA.  We represent millions of patients, consumers, researchers, and medical professionals.

Our coalition has opposed previous efforts to allow the promotion of off-label use, and we still continue to strongly oppose it.

There are valid reasons for doctors to prescribe treatments off-label.  Many drugs are prescribed off-label as common, accepted practice. However, doctors and patients should discuss the use of these treatments with a clear understanding of the level of evidence, the doctor’s reasoning, and the risks.

Patients should have informed consent, which includes signing a piece of paper that explains that the product is not approved by the FDA for the indication that the product is being prescribed for.  It should also include a discussion of what that means regarding the lack of objective evidence that the benefits outweigh the risks for most patients.  That is the critical calculus that the FDA must always balance.

We are concerned that the FDA does not have the resources to monitor such increased off-label promotion and patients will be harmed.

In our view, the off label promotion for medical devices has one primary goal: To increases the use of medical products for conditions and indications for which the product is not approved by the FDA.  It is not approved because the sponsor has not adequately proven to the FDA that the product is safe and effective for that particular indication.  The result can be that:

  1. Patients will be more likely to be prescribed treatments that are not effective or safe for their specific condition.
  2. Patients also may be more likely to be prescribed treatments that are may be more likely to harm than to help them.

It is virtually impossible for FDA or any other agency to ensure that off-label communications are uniformly truthful and scientifically sound.  That would be an extremely resource-intensive task at an agency where resources are often stretched to the very limit.

Representatives from our collation have testified at FDA advisory committees regarding medical products.  Some of these products have looked promising in the companies’ presentations trials, but then FDA reviewers identified key problems that raised major concerns about the study or the underlying data.  In other words, the entire FDA process is based on the assumption that a sponsor’s analysis is not always unbiased and of sufficient scientific quality to merit FDA approval.  That is why we believe in the critical importance of FDA’s role and why we oppose the promotion of medical products for off-label uses.

As I mentioned, off-label uses are already widespread and commonplace.  For many drugs and devices, in fact, a significant proportion of use is off-label.  Unfortunately, research shows that off-label uses increase the number of adverse events.  If promotion of off-label usage is allowed, we believe, more patients will inevitably be harmed.

Increasingly, FDA is approving drugs and devices based on smaller, preliminary studies.  In the case of medical devices, the vast majority are not required to do any clinical trials.  Frequently, the apparently promising results of small exploratory studies or clinical experiences fail to be confirmed when further tested with a larger, controlled trial.  Sponsors already have few, if any, incentives to robustly test their product once it is on the market, either for its approved indication or for other indications.

Some observers have suggested that increased transparency or data sharing about clinical trials could allow practitioners and patients to evaluate clinical trials themselves.  Supposing that there is sufficient data for us to evaluate the data and that it is not selectively released, we believe that many medical professionals and nonprofit organizations have neither the time nor the expertise to do so.

Those advocating for off-label promotion of their products contend that such claims are protected as free speech and that restriction off-label promotion is an unfair abridgement of that free speech.  As a lapsed and recovering journalist, I’m a big fan of the First Amendment.

However, if it is true that not allowing promotion of off-label uses of medical devices is a restriction of free speech, then why do companies which settle lawsuits with patients who have been harmed insist on non-disclosure agreements that make it impossible for those patients to exercise their own free speech?  Why are patients who settle lawsuits so frequently not allowed to speak publicly about what happened to them?  We believe such restrictions are also another barrier or impediment to identifying patterns of adverse events involving medical devices.

Companies don’t have an incentive to disseminate clinical trials that show that their product does not work.  It’s relatively easy to find cases where a product worked for at least one or a few patient with a simple internet search.  Such information is more difficult to find where patients were harmed, because it is either not published or not promoted.

The history of promoting off-label use in the pharmaceutical world has been dismal.  This list of major violations includes almost all of the major drug firms.  Each has been successfully sued for improper off-label marketing tactics.  Collectively, they’ve been fined hundreds of millions, if not billions, of dollars.

As former chief of oversight and investigations for the Senate Special Committee on Aging. I’ve seen the devastating human impact of the over-use and massive off-label prescribing of antipsychotic drugs in nursing homes, for which multiple pharmaceutical companies have been fined hundreds of millions of dollars.

Nevertheless, those hefty fines and legal settlements have not discouraged off-label promotional practices, and many violations have been made by repeat offenders.  Neither FDA nor the Justice Department has been able to curb these abusive off-label practices with lawsuits and huge fines.  It is hard to believe that legitimizing off-label promotion for devices will not make these type of abuses even more widespread.

Proponents of device of-label promotion have argued that FDA should allow promotion of off-label uses, but that the agency must insure that it is “scientifically sound, responsibly presented, and provides as full an understanding as possible about the limitations of the available evidence.”  That sounds reasonable but it apparently assumes that the clinical trial results that the company is distributing are truthful and aren’t distorted by selectively reporting information, or have serious flaws that may not be apparent.

In summary, we strongly oppose allowing the promotion of device products for off-label uses. We believe that there are not adequate safeguards to allow such promotion to be limited to only scientifically sound, complete, and unbiased data.

While admittedly some off-label use is accepted and has positive outcomes, as you are hearing from patients’ testimonies at this meeting, many have been harmed by off-label use.  The patient Jeremy Lew related yesterday the painful details of coming very close to death or complete paralysis because a device was surgically inserted into his neck which was not approved by FDA for that purpose, but was advertised as being approved.  As you’ve heard, this is not an academic or legal debate only—there are huge human costs and immense suffering.

Our concern, simply stated, is that allowing off-label promotion will cause more patients to be harmed than helped.  When companies submit data to the FDA, agency reviewers have the expertise and responsibility to thoroughly review such data.  That careful process is what has kept Americans more safe from medical harm since the creation of FDA more than seventy-five years ago.

Allowing off-label promotion conflicts with that delicate balance and tends to remove an important incentive for companies to complete high-quality clinical trials for new indications; which would produce reliable data of both efficacy and safety.

I worked in the FDA Commissioner’s office for seven years, and I know the dedication that agency employees have.  They will get the job done when they have access to the appropriate resources and information necessary to do perform their life-critical responsibilities.   Thank you.

Letter to Senators on the Innovation for Healthier Americans bills

November 8, 2016

United States Senate
Washington, DC 20510

Dear Senator _____:

The undersigned nonprofit organizations represent members of the Patient, Consumer and Public Health Coalition, which includes more than 6 million healthcare providers, public health experts, and consumer and patient advocates.  We respectfully urge you to not advance the Senate’s Innovation for Healthier Americans bills or the House’s 21st Century Cures Act during the lame duck session of Congress.  While the House version of the legislation provides additional funding for the National Institutes of Health (NIH), both the House and the Senate versions contain more controversial measures which would lower safety and approval standards for drugs and medical devices at the Food and Drug Administration (FDA).

A number of leading medical experts, including a former Commissioner of the FDA, Dr. David A. Kessler, believe that the bill “could lead to the approval of drugs and devices that are less safe or effective than existing criteria could permit”. We believe that the far-reaching measures described below will significantly impact public health and safety and should therefore not be rushed into law in the final brief weeks of this Congress.

For example, the PATH Act, in both the House and Senate versions, would allow antibiotics to be approved based on minimal evidence of safety and effectiveness through a “limited population” approval pathway.  Unfortunately,  these antibiotics could then be widely advertised in order to increase sales, even though they may be much less safe or effective than older, less expensive antibiotics.

The MEDTECH Act, also in both Senate and House (Section 2241)  versions, would prevent the FDA from collecting adverse events caused by flawed electronic medical records and decision support software.  A study by the National Center of Health Research found that these types of health IT devices can cause like-threatening problems when they miscalculate incorrect drug dosages for chemotherapy drugs and other treatments.

The Advancing Breakthrough Devices for Patients Act, versions of which are in both House and Senate bills, would encourage shorter and smaller clinical trials for medical devices. These smaller studies make it impossible to include sufficient numbers of women, men, seniors, and racial and ethnic minorities. Moreover, a recent study of high-risk medical devices found that the median number of participants is currently only 65 patients, which is already too small to adequately evaluate safety and effectiveness for both men and women, let alone for elderly men and women compared to young adults, or for people of color. The House bill is even worse; for example, Section 2221 would permit companies that manufacture life-saving devices such as heart valves and stents, to be modified without submitting the new devices for FDA approval, as is now required.

Alarmingly, the bill in its current form also allows anecdotal and easily manipulated sources of health data to be used to approve new drugs (Section 2121).   It effectively would eliminate clinical trial drug testing for new medical uses (called “indications’ in the bill).  This measure also would result in the widespread use of medications for uses that are not approved by FDA, causing inevitable patient harm.  (Section 2012: Facilitating responsible communication of scientific and medical development).

In addition to the extensive dilatory effects on FDA’s ability to protect the public health, the bill also extends exclusivity provisions for the pharmaceutical industry, discouraging the use of cheaper generic drugs, and having the practical effect of increasing or maintaining higher drug prices, at a time when the vast majority of Americans are frustrated with and angered by rapidly increasing drug prices.  For example, the Advancing Hope Act, passed by the Senate, would continue the existing pediatric priority review voucher program through 2022. A recent GAO review of the program concluded that the program has questionable benefit.  And, by allowing drug makers to buy a priority review, the bill undermines FDA’s ability to set its work priorities based on public health needs.

There also is serious concern concerning whether the additional $550 million dollars allocated to FDA by the House version of the bill would be sufficient to carry out the extensive mandates outlined by the legislation.  FDA already is severely under-funded and cannot absorb unfunded mandates without dire consequences to its regulatory effectiveness and ability to protect public health.

The House version of the bill also weakens reporting requirements for the bipartisan Physician Payments Sunshine Act (“Sunshine”), a medical payments disclosure measure which is being successfully administered by the Centers for Medicare and Medicaid (CMS).  The Sunshine Internet data base has provided the public with a useful and readily accessible transparency tool that can be used to discover which physicians and surgeons are accepting payments from the pharmaceutical and medical device industry, how much, and for what purpose.

Until the Sunshine data base was established a few years ago, doctors were accepting hundreds of millions of dollars annually in undisclosed payments from industry, much of which was intended to influence drug prescribing practices and the physicians’ brand choice of medical devices.  The Sunshine Act does not prohibit or discourage these payments, merely makes them part of the public record, and allows patients and consumers to decide whether such payments influence their own medical treatment and choice of physicians.

In addition to weakening safeguards for patients and increasing the availability of treatments that are not proven either safe or effective, neither the House nor Senate bills include provisions to lower drug prices.  A recent study by a researcher at the National Cancer Institute found that most cancer drugs approved during a recent 5-year period are not proven to improve the health of cancer patients.  The National Center for Health Research assessed the cost of those ineffective drugs and found that they cost the same or more as cancer drugs that are proven to work.  A recent letter to Congress by a coalition of more than a dozen labor and public interest groups asked the Congress to delay consideration of the Cures/Innovation bills until there are measures included to lower drug prices.  We agree, but we also point out that several provisions in these bills would have the opposite impact, since many new drugs would be sold without clear evidence of efficacy, and yet those new drugs will inevitably cost more than older, more effective and less expensive treatments.

Sincerely,

National Center for Health Research
American Medical Student Association
American Medical Women’s Association
Annie Appleseed Project
Breast Cancer Action
Breast Cancer Coalition
Center for Medical Consumers
Connecticut Center for Patient Safety
Institute for Safe Medication Practices
Jacobs Institute of Women’s Health
Mothers Against Medical Error
MRSA Survivors Network
National Physicians Alliance
National Women’s Health Network
Our Bodies Ourselves
Quinolone Vigilance Foundation
TMJ Association
Washington Advocates for Patient Safety
WomenHeart
Woody Matters

For more information, please contact Jack Mitchell at jm@center4research.org.

Comments to FDA against removal of the black box warning for Chantix

Thank you for the opportunity to speak today. My name is Dr. Stephanie Fox-Rawlings and I am speaking on behalf of many members of the Patient, Consumer, and Public Health Coalition. The Coalition includes nonprofit organizations representing millions of patients, consumers, researchers, and doctors united to ensure that medical treatments are safe and effective.  The coalition does not have paid staff and does not accept funding from any outside sources, so I have no conflicts of interest.

Pfizer is once again asking the FDA to remove the black box warning that Chantix is associated with serious adverse events such as depression, hostility, agitation, suicidal thoughts, attempts, and completions. They want to replace it with the statement that these are associated with quitting smoking. They also want to remove the warning that there may be an increased risk for patients with a psychiatric illness. GlaxoSmithKline wants to remove REMs requirements for Zyban. They based these changes on one large, poorly executed clinical study.

It is important to point out that these black box warnings were initiated because of the enormous number of extremely serious psychiatric adverse events, including suicide and aggressive behaviors, associated with these smoking cessation products.  Research has also confirmed that some patients have extreme psychiatric responses that can be deadly to themselves and to others.  The purpose of these warnings is to let patients know that if they seem to be having uncontrollable feelings when on these drugs, that there is a good chance that getting off the drugs will solve the problem almost immediately.

Pfizer’s study concludes that Chantix does not have these risks but the FDA reviewers have clearly shown that there are extensive problems with how the data were collected and analyzed:

#1: The study measured psychiatric problems with something called the Neuropsychiatric Adverse Event Inventory (NAEI).  This is not a validated test so it was only supposed to be used to start the conversation about psychiatric symptoms.  Instead, it was used as a unvalidated checklist, which contributed to inaccurate data.  For example, it did not identify cases of suicidal behaviors that were identified by validated scales.

#2.  When patients reported psychiatric problems, those problems were not coded consistently.  The FDA pointed out that the staff doing interviews and coding were not always trained mental health professionals and didn’t seem to understand some of the categories they were coding.  Even worse, their very subjective measures of severity were sometimes completely incorrect: such as a patient who became severely depressed being coded as having a mild problem from taking Chantix.

#3: Since 70% had tried to quit smoking previously using one of these drugs, the study was biased toward people that had previously tolerated the drug.  This would drastically underestimate the percentage having serious adverse reactions.   In addition, anyone with suicidal thoughts or behaviors in the past year or anyone with self-injuring behaviors were excluded. While these patients should not be treated with a drug that could make these worse, this could again bias the results to make the drugs seem safer than they really were.

In summary, patients deserve access to smoking cessation treatments, but they also deserve warnings about the risks.  There remains considerable credible evidence that some patients are severely harmed by Chantix and Zyban, and those patients’ lives depend on warnings about the risks, so they will recognize that sudden suicidal, paranoid, or violent thoughts are side effects of the drugs.

Thank you for your time and consideration of our views.

 

Coalition Letter to Senators regarding the Senate’s Biomedical Bills (21st Century Cures companion legislation)

July 5, 2016

Dear Senator,

As members of the Patient, Consumer, and Public Health Coalition, we are writing to express our views as consumers, physicians, scientists, and public health experts regarding the Senate’s biomedical bills (21st Century Cures companion legislation).

We want all Americans to have the best possible medical treatments but we are concerned that the primary focus of these bills is on getting medical products to market more quickly, instead of making sure they are safe and effective. Whether creating a new expedited pathway for devices (which already are approved based on much lower standards than drugs) or deregulating health IT software, for example, patients will be at risk.

We are very concerned about unintended consequences of expedited approvals. If drugs are approved based on preliminary evidence and then later found to be ineffective or unsafe, potentially billions of dollars could be wasted by Medicare (taxpayers) and private insurers. Consumers are worried about skyrocketing drug prices. A Bloomberg analysis found that 30 of 39 drugs they reviewed had price increases more than double the rate of inflation from 2009 to 2015, even after discounts were factored in.[1]Innovative new drugs and devices will do nothing to improve health or save lives if they don’t work or if most Americans can’t afford them.

The Food and Drug Administration’s (FDA) primary mission is to protect the public health by “assuring the safety, efficacy and security” of drugs, biological products, and medical devices.[2] As a Senator, it is critical that any legislation you support advances the FDA’s role in protecting public health. Below are bills that we urge you to oppose followed by bills we would like you to support.

We urge you to oppose:

The MEDTECH Act (S. 1101)

The MEDTECH Act removes health IT software from FDA’s regulatory oversight. If this bill becomes law, the FDA would no longer gather information about life-threatening flaws in medical software and no longer have the authority to recall those deadly devices. Dangerous flaws are commonly caused by glitches in software design but can also result if the software is easily hacked. A National Center for Health Research study found that if medical software is removed from FDA regulatory oversight, millions of patients would be at risk from defective software. For example, oncology electronic medical record systems were recalled in the past because they calculated and recorded incorrect drug dosages. Clinical decision support systems used during surgery were recalled because they erroneously switched patient data and failed to warn physicians about dangerous drug reactions.

Advancing Breakthrough Devices for Patients Act (S. 1077)

The Advancing Breakthrough Devices for Patients Act lowers standards for safety and effectiveness for devices. Only 3% of all medical devices are studied in clinical trials, and most are already small. This bill would encourage even smaller clinical trials, which would inevitably have fewer women, people of color, and patients over age 65 (often too few to ensure that the device is safe and effective for those groups). The bill would also push FDA to rely on post-market studies rather than ensuring safety and effectiveness before hospitals and patients pay for the devices. Remember that these are already the riskiest 3% of medical devices! As a result, public and private insurers will spend billions on medical devices that might later be found to be unsafe or ineffective.

The PATH Act (S. 185)

While the amended version that was voted out of the HELP Committee was greatly improved over the 21st Century Cures version, we do not support the concept of a limited population approval pathway for antibiotics. Antibiotics approved via a pathway such as this will have minimal evidence of safety and effectiveness but will inevitably become widely prescribed to more general populations with less severe infections. As a result, resistance will develop and a potentially promising drug will become ineffective.

The Advancing Hope Act (S. 1878)

The ability of the Advancing Hope Act to stimulate innovation through the issuance of priority review vouchers is questionable and it does not efficiently use FDA resources to benefit public health. The priority review vouchers have so far been used for drugs already under development in the U.S. or already licensed in other countries.[3]Furthermore, by allowing sponsors to buy a priority review, the bill removes FDA’s ability to set its work priorities and resource allocations based on the public health merit of the project.[4] In a time of dangerous threats like Zika and Ebola virus, we expect our government agencies to be able to prioritize public health, not to be bound by priority review vouchers that were sold to the highest corporate bidder.

The Combination Product Regulatory Fairness Act (S. 1767)

We strongly oppose the Combination Product Regulatory Fairness Act because it would result in more combination products being classified as devices and thus reviewed with less scientific evidence when it would be better for patients if the FDA used the more rigorous drug review process. This bill also restricts the FDA’s ability to later seek additional clinical data if it discovers new information related to safety and effectiveness. This is dangerous for patients.

The REGROW Act (S. 2689)

While not included in the bills voted out of the Senate HELP Committee, the REGROW Act has been mentioned as a priority by the Republican leadership for inclusion in the Senate biomedical bills. This bill would allow complex biologic therapies to be conditionally approved based on very preliminary evidence and then prescribed to patients without proof that the new therapy actually works or is safe. Notably, the Alliance for Regenerative Medicine (ARM), which includes many of the best regenerative medicine researchers, does NOT support the REGROW Act. If passed, this Act could lead to CMS wasting billions of dollars on medications that were approved by the FDA but do more harm than good. Although strongly criticized by researchers and ethicists, this bill has support from a billionaire who has donated $2 million to a Senate super-PAC.

We urge you to support:

The Preventing Superbugs and Protecting Patients Act (S. 2503)

Drug-resistant infections from contaminated duodenoscopes and other reusable devices have hurt and killed many people throughout the United States. This legislation and the safety recommendations in the recent HELP minority staff report will help prevent this from happening in the future. We strongly urge you to support this legislation that will reduce and eliminate these deadly infections.

The Advancing Research for Neurological Diseases Act (S. 849)

The bill would provide a foundation for the Department of Health and Human Services (HHS) to learn more about the many factors involved in neurological diseases, such as geographic clusters of diagnoses, variances in the gender ratio, disease burden, and changes in health care practices. This could truly be a game-changer for people suffering from neurological diseases and provide critical information to researchers as they work on new treatments and cures.

As you consider combining only the best of these bills into a comprehensive legislative package, it is essential to provide additional mandatory funding for the NIH and FDA so that there are no unfunded mandates in the legislation and there is sufficient support to develop and monitor safe and effective medical treatments.  We particularly urge substantial new funding for the NIH to develop new antibiotics targeted to resistant bacteria, as well as to FDA and CDC to ensure stewardship of antibiotics already on the market. We must ensure that these institutions remain at the forefront of science and medicine for years to come and that patients can trust their drugs and medical devices to improve their health rather than harm it.

 

Sincerely,

Breast Cancer Action

Mothers Against Medical Error

MRSA Survivors Network

National Center for Health Research

National Consumers League

National Women’s Health Network

Quinolone Vigilance Foundation

The TMJ Association

Washington Advocates for Patient Safety

Woody Matters

 

[1] Langreth R, Keller M, Cannon C (June 29, 2016). Decoding Big Pharma’s Secret Drug Pricing Practices. Bloomberg. Available at: http://www.bloomberg.com/graphics/2016-drug-prices/.

[2] Food and Drug Administration. FDA Mission from the agency’s Web site. Accessed March 3,2016.http://www.fda.gov/downloads/aboutfda/reportsmanualsforms/reports/budgetreports/ucm298331.pdf.

[3] Branswell H (November 28, 2015). How a system to help treat rare diseases broke down,STAT.http://www.statnews.com/2015/11/28/priority-review-vouchers-rare-diseases/.

[4] McCaughan M (October 6, 2015). Priority Review Vouchers: FDA Has “Concerns,” Pharma & Medtech Business Intelligence.​

Coalition letter urging Senators to oppose S. 2912, the Trickett Wendler Right to Try Act of 2016

June 14, 2016

Dear Senator,

As members of the Patient, Consumer, and Public Health Coalition, we are writing to express our views as consumers, physicians, scientists, and public health experts regarding S. 2912, the Trickett Wendler Right to Try Act of 2016. We strongly urge you to NOT co-sponsor this bill. This bill is bad for patients, bad for doctors, bad for drug development, and bad for science.

As you may know, the history of the FDA is a history of Congress responding to medical tragedies by requiring FDA to do more to protect patients from harmful medical products. Thalidomide birth defects and deaths and infertility from the Dalkon Shield IUD are just two of many examples. Although the AIDS crisis resulted in a more flexible approach for deadly diseases for which there were no treatments, today’s HIV/AIDS advocates are among the FDA’s strongest supporters, because the scientific evidence that FDA required of pharmaceutical companies resulted in effective treatments and prevention strategies. The FDA’s essential role continues to be to achieve a balance between patients’ rights and societal good. It is critical that, in your role as a Senator, you support the agency in upholding this delicate balance.

The idea behind this bill and other Right to Try laws is to give terminally ill patients access to experimental drugs that have passed phase I testing – testing that is often done on healthy volunteers, not people with serious illnesses. While this type of legislation promises cures, it offers false hope. Since most phase 1 trials include less than 30 patients and are designed only to identify the most immediate side effects, they provide very little information about the drug’s safety and effectiveness. In fact, most drugs with promising phase 1 test results are later found to be too risky or ineffective for patients to use. This is especially true for cancer drugs. Under the proposed bill, desperate patients are likely to be exploited by unethical companies that want to sell their unproven treatments at prices that would bankrupt many families. Health insurance companies will not pay for these unproven treatments – if they did, insurance premiums would skyrocket as patients harmed by unproven treatments required more expensive remedial care.

In the recent past, access to experimental bone marrow transplants for breast cancer was expedited due to an early benefit seen in preliminary data. It was not until many women were harmed and some even died that researchers realized a terrible mistake had been made. If doctors and patients can be fooled into trying such a painful and toxic treatment, imagine how often patients would be fooled by treatments that are less painful but ineffective and expensive snake oil.

This legislation would subject patients to a great risk of harm and they would have no legal recourse if things go wrong. In fact, this bill and similar state Right to Try laws reflect the libertarian philosophy of the Goldwater Institute that created them: the patient is on his or her own without any protections or safeguards. The bill explicitly states that drug and device companies as well as physicians cannot be held liable for any tragic outcomes, even if the company or a physician misled the patient. Even worse, if a patient suffers a terrible medical complication from a Right to Try treatment, the insurance company would not need to pay for the medical care that is needed to treat that complication. The only thing worse than a terminal illness is being terminally ill and suffering a major complication as the guinea pig in an experimental treatment that you had to pay for.

There are many other problems with the bill, but perhaps the most important thing for you to know is that the FDA’s current compassionate use program already provides patients with the opportunity to try experimental drugs, while offering some protections to patients and society. For example, while physicians and drug companies are required to report the outcomes of experimental treatments obtained through the FDA’s compassionate use program, Right to Try laws do not carry such stipulations. Indeed, this bill strips all protections from patients who would use it. Bypassing the oversight of the FDA is not in the best interest of patients or the public health.

The one shortcoming of the FDA’s current compassionate use (“expanded access”) program is also in the Right to Try bill: the company is not required to provide the experimental drug to the desperate patient. In some cases, that’s because the company doesn’t have enough doses to provide to patients not in a clinical trial, and in other cases, the company believes that the patient is more likely to be harmed by the product than helped by it.

In conclusion, Right to Try laws such as S. 2912 will do more harm than good for patients and society. The bill is opposed by experts in the field as well as by legitimate drug companies. We urge you to oppose the Trickett Wendler Right to Try Act of 2016.

Sincerely,

American Medical Women’s Association

Connecticut Center for Patient Safety

DES Action

Jacobs Institute of Women’s Health

MedShadow Foundation

National Center for Health Research

National Physicians Alliance

 

 

The Patient, Consumer, and Public Health Coalition can be reached through Tracy Rupp at 202-223-4000 or tr@center4research.org.

 

Coalition’s comments to the FDA on User Fees for Over-the-Counter Drugs

June 10, 2016

Comments of Members of the Patient, Consumer, and Public Health Coalition at the Public Meeting on OTC Monograph User Fees

Thank you for the opportunity to speak today.  My name is Paul Brown and I am speaking on behalf of 10 members of the Patient, Consumer, and Public Health Coalition.  Our informal coalition of nonprofit organizations represents the interests of patients, consumers, health-care professionals, scientists, and public health experts.

We support providing FDA with additional resources through the implementation of OTC user fees, so the agency can fulfill its mission of protecting the public from dangerous and ineffective OTC products.  Additional funding will help FDA to finalize the remaining OTC monographs, and allow patients and consumers to have confidence in the OTC products they use every day.

Since the OTC drug review process was established in 1972, FDA has struggled to complete the safety and efficacy evaluations of ingredients used in OTC drug products.  More than 40 years later, the monograph process still has not been completed for all ingredients and conditions of use.

As a result, many OTC products without a general recognition of safety and effectiveness (GRASE) determination continue to be marketed, leaving millions of American vulnerable to potentially unsafe products.

A staff of only 18 people cannot effectively regulate 800 active ingredients for over 1,400 different therapeutic uses. We are particularly concerned about how the current process limits FDA’s ability to require new warnings or other labeling changes to address emerging safety or effectiveness issues in a timely manner.

We strongly urge FDA to include funding in user fees to address emerging safety and effectiveness issues.  FDA needs resources to provide ongoing surveillance of marketed products and move quickly when safety signals arise.

This is especially important for products used by children. When the monographs were first developed in the 1970s, FDA lacked specific data on use in infants and children.  So, FDA did what was scientifically customary at the time and extrapolated the data by simply reducing adult doses by a percentage.

Our understanding of pediatric dosing has grown since then and, as a result, data from actual use in the pediatric population is preferred.  Many products continue to be given to infants and children without sufficient safety and effectiveness data. OTC user fees are needed to support the reexamination of the use of these products in children.

OTC product user fees should also support the development of product formulation standards. The monographs set forth the conditions under which a specific active ingredient used in a drug product is generally recognized as safe (GRAS) and generally recognized as effective (GRAE) and not misbranded.

The monographs, however, generally do not dictate what other non-active ingredients can be added, or other aspects of the formulation. For example, we know that many product formulation variables affect how much of a tablet’s medication dose is absorbed. The regulatory science behind generic drugs has shown us that excipients and manufacturing quality control must factor into the determination of a product’s safety and effectiveness. Therefore, we recommend development of standards for drug products, not just their ingredients; and we urge FDA to include funding for this in user fees. (As United States Pharmacopeia (USP) has recommended.)

A user fee system for OTC drugs will have to take into account the way OTC drugs come to market.  Since the monograph system is ingredient-based and not product-based and, since sponsors of monograph drugs are not required to obtain FDA approval prior to marketing, the fee structure will have important differences as compared to that used by the prescription drug programs.

We recommend that user fees be structured as a product listing fee based on a sliding scale proportionate to the complexity and reviewing resources required. We feel this mechanism would provide the agency with a stable and predictable source of funding for the OTC division.

We would avoid structuring the fee as a facility fee since it may have the unintended consequence of pushing sponsors to consolidate operations into as few facilities as possible. This could impact the supply chain and cause OTC drug shortages, if a facility is removed from operation.

In summary:

  • We support the establishment of a user fee program for OTC drugs so that all OTC monographs can be finalized.
  • We urge you to include funding in user fees to address emerging safety and effectiveness issues as well to reexamine use of certain OTC products in infants and children. Additional resources are critical to protect public health.

Thank you for your attention.

American Medical Student Association
MAME
MedShadow
MISSD
National Center for Health Research
Our Bodies Ourselves
Quinolone Vigilance Foundation
The TMJ Association
Washington Advocates for Patient Safety
WoodyMatters

Coalition Comments on FDA Draft Guidance for Generic Abuse-Deterrent Opioids

May 24, 2016

Comments of members of the Patient, Consumer, and Public Health Coalition on “General Principles for Evaluating the Abuse Deterrence of Generic Solid Oral Opioid Drug Products: Guidance for Industry”

Docket No. FDA-2016-D-0785

Thank you for the opportunity to comment on the draft guidance, “General Principles for Evaluating the Abuse Deterrence of Generic Solid Oral Opioid Drug Products: Guidance for Industry.” Development of such products is of great public health importance as a strategy to help make pain medications more affordable to those who truly need them while also reducing opioid abuse.

The Patient, Consumer, and Public Health Coalition is an informal coalition of nonprofit organizations representing the interests of millions of patients, consumers, health-care professionals, scientists, and public health experts. The comments and recommendations of the members of the Coalition follow:

  1. Avoid use of the misleading term “abuse-deterrent”

While the guidance does not specifically address labelling, we urge FDA to avoid use of the term “abuse-deterrent” since it is often misinterpreted to mean “addiction-deterrent.” In fact, a recent study found that nearly half (46%) of physicians think that abuse-deterrent formulations make these medications less addictive than others.[1] Instead, labelling language that more accurately captures the product’s abuse-deterrent properties should be used. For example, if a pill has been made difficult to crush, it should be labeled “crush-resistant.” It is important to use precise language because “abuse” and “addiction” are often used interchangeably.

  1. Provide guidance for all types of abuse-deterrent technologies

The draft guidance includes recommendations to industry on the studies needed to show that a generic opioid is no less abuse-deterrent than the brand-name (or reference) drug, with respect to all potential routes of abuse. It provides testing recommendations for four of the seven categories of abuse-deterrent technologies described in FDA’s “Abuse-Deterrent Opioids: Evaluation and Labeling” guidance: solid oral opioid drug products formulated to incorporate physical or chemical barriers, agonist/antagonists, aversive agents, and combinations of two or more of these technologies. Since this field is continually evolving, we urge the FDA to also develop guidance for products in the remaining three categories so that patients have access to a variety innovative pain management therapies that are also safe and effective.

  1. Require the generic product to show it is not less abuse-deterrent than the reference product with respect to all potential routes of abuse

We agree with FDA that it is necessary for a generic manufacturer to provide studies that show that their product is not less abuse-deterrent than the reference product with respect to all potential routes of abuse. This will help minimize the risk of shifting abuse to another potentially more dangerous route of abuse (e.g. oral abuse to intravenous abuse). It will also prevent the approval of a generic opioid product that is less abuse-deterrent than the reference drug, which could lead opioid abusers to preferentially seek out and abuse generics. It is critical that, in attempting to solve one problem, we avoid creating a new one.

  1. Include a control product in tampering studies

Since the abuse-deterrent properties of currently approved drug products can eventually be compromised, it is important to have a good understanding of the type of manipulation or tampering that renders the opioid non-abuse-deterrent. Therefore, we agree with FDA’s recommendation to include a control product (i.e. a non-abuse-deterrent version of the reference product) in studies of abuse-deterrence. This will help provide a more accurate understanding of the product’s ability to deter abuse.

  1. Apply extra scrutiny to Tier 1 studies

As stated in the draft guidance, FDA recommends that applicants follow a tier-based approach when comparing a generic product to a reference product. This tier-based approach allows for hierarchical testing, starting with simple and gentle manipulations of the product (Tier 1) and progressing to more destructive mechanical and chemical manipulations (Tiers 2, 3, 4, etc.). Using this method, all of the null hypotheses in Tier 1 must be rejected before testing the null hypotheses in higher tiers. For that reason, it is essential that Tier 1 studies are rigorously conducted and documented. We urge FDA to apply extra scrutiny to these Tier 1 studies to ensure the statistical integrity of the tier-based approach.

  1. Enforce post-marketing real-world epidemiological study requirements for reference opioids

While not specifically addressed in this guidance, we strongly urge the FDA to enforce post-market study requirements for reference drugs. Since generic abuse-deterrent opioid formulations use the branded product as the reference for actual ability to deter abuse, it is critical that FDA follow through on its requirement for real-world post-marketing studies. An unsafe and ineffective reference product will result in unsafe and ineffective generic products. Sponsors of brand name products with approved abuse-deterrent labeling must complete the required long-term epidemiological studies to assess their effectiveness in reducing abuse in practice or risk having their approval revoked.

Conclusions

In summary, we applaud the FDA for providing guidance to industry to advance the regulatory science behind abuse-deterrent oral opioid formulations. We agree with many of the recommendations in the guidance and urge the FDA to consider our recommendations regarding the use of the term “abuse-deterrent”, the development of guidance addressing additional abuse-deterrent technologies, the scrutiny applied to Tier 1 studies, and the enforcement of post-marketing study requirements for reference products.

Sincerely,

American Medical Women’s Association

Cancer Prevention and Treatment Fund

Connecticut Center for Patient Safety

MedShadow Foundation

National Consumers League

The TMJ Association

Washington Advocates for Patient Safety

 

References

[1] Hwang CS, Turner LW, Kruszewski SP, et al. Primary Care Physicians’ Knowledge And Attitudes Regarding Prescription Opioid Abuse and Diversion. Clin J Pain. 2016 Apr;32(4):279-84.