Letter to Congresswoman DeGette Expressing Concerns About 21st Century Cures

May 19, 2015

The Honorable Diana DeGette
United States House of Representatives
Washington, DC 20515


Dear Congresswoman DeGette,

As members of the Patient, Consumer, and Public Health Coalition, which includes organizations representing patients, consumers, health professionals, and scientists,  we are writing to express our strong concerns about the 21st Century Cures legislation.  At the recent E&C Subcommittee on Health markup of the 21st Century Cures Act, Committee Ranking Member Frank Pallone stated that the Act was “far from a finished product,” and the Health Subcommittee Ranking Member Gene Green said there is “still work to do.”  We agree. Several sections of the Act would lower standards for the approval of antibiotics, medical devices, and most prescription drugs – putting patients at unnecessary risk of injury or death.  A few of our specific concerns are below.

If these provisions are fixed in Committee, we will be able to support the Bill.  But as currently written, the FDA provisions of 21st Century Cures violates the basic tenet of medical care–“First, do no harm.” The FDA provisions are more geared toward helping industry than helping patients. Patients deserve an FDA that keeps unsafe and ineffective pharmaceuticals and medical devices (including software) off the market by evaluating their risks and benefits as carefully as possible, in addition to as quickly as possible.  These revisions are necessary to provide those safeguards for all patients.

  1. Section 2021: Drug Development Tools

The best evidence that a drug will help patients is based on its impact on patients’ health.  Sometimes “surrogate endpoints” can be used instead of patient health, if there is solid evidence that the surrogate predicts patients’ health.  However, Section 2021 encourages the use of surrogate endpoints to support accelerated approval of a drug even if there is no solid evidence that patients would benefit.  The vague language of this section says that the drug would only have to be “reasonably likely” to predict safety or effectiveness.  Unfortunately, many “likely” measures of benefit have later been found to have no benefit or even to be harmful.

  1. Subtitle D: Modern Clinical Design, Section 2062-63: Evidence from Clinical Experience and Streamlining Data Review

Current FDA standards usually require evidence of safety and effectiveness in clinical trials of patients.  This section would encourage much lower standards, including the belief of one or more physicians or patients that a product is safe or effective.  That’s the definition of “clinical experience.”  This might seem justified because the provision focused on new uses of previously approved drugs.  However, just because a product is approved for one type of treatment doesn’t mean it is safe or effective for other types of treatment.  The FDA approves drugs by weighing risks compared to benefits.  For example, a drug that can save a cancer patient might be approved despite potentially fatal side effects, but that same drug would not be considered safe enough for a stomach ache.  Similarly, a drug that is effective for an otherwise fatal brain cancer might be approved despite substantial risks, but might be much less safe or effective than existing breast cancer treatments.  That’s why the FDA approves drugs and devices for specific treatments, not for all treatments.

The bill would also allow clinical experiences to be used to prove safety and effectiveness instead of post-market studies.

The bill further erodes FDA standards by allowing drug companies to submit short summaries about the safety and effectiveness of already approved drugs, instead of providing actual evidence to support what is stated in the summaries.  This would apply to new indications, even when drugs were approved in expedited pathways based on preliminary, inconclusive data.

Even more egregious, the bill states that “nothing in this section prohibits the Secretary from using evidence from clinical experience for purposes not specified in this section,” which suggests clinical experience could possibly be used as evidence to support FDA approval for new medical products as well.  Overall, the wording of these sections is so vague that it could eviscerate the FDA’s ability to make informed judgments about the safety or effectiveness of any drug, device, or vaccine.

  1. Sections 2121: Approval of Drugs for Use in a Limited Population of Patients

This section would create a new pathway for approving antimicrobials that would discourage the use of large, well-designed, randomized, controlled clinical trials, which are the gold standard for assessing safety and effectiveness.  Instead, the proposed pathway would force the FDA to enter into a written agreement early in the clinical development program that would allow approvals based on preliminary, uncontrolled clinical studies alone. The drugs would be tested on small numbers of patients (a limited population) but could then be prescribed for all patients without clear evidence that it is beneficial for all patients.  That would be harmful to patients.

It is important to note that while antibiotic resistance is a public health problem that is related to the lack of financial incentives to develop new antibiotics, the issues are different for antifungals.  If Congress lowers the standards for antifungals as described in this provision, that would be very harmful to patients without providing a benefit to patients.

  1. Section 2123: Encouraging the Development and Use of New Antimicrobial drugs

This section would pay a bonus to hospitals to prescribe new antimicrobials. The more widely these drugs are used, the faster bacteria and fungi will become resistant to them.  To preserve these drugs, hospitals should be given incentives to avoid using new antimicrobials when not medically necessary and to instead prescribe older antibiotics whenever possible. This provision does the opposite, encouraging overuse of new antimicrobials by paying a financial bonus to hospitals each time they use one.

New antifungals are very expensive and this bonus would exacerbate that situation.  While new antibiotics have the potential to treat resistant bacteria, and thus research investment is important, the overall effect of this provision would be to reduce, rather than expand, the availability of effective antibiotic drugs.

In summary, this section would put patients at risk by reducing the availability of effective antimicrobials, and also places additional financial strain on Medicare.

  1. Section 2151: Extension of Exclusivity for a New Indication for Rare Disease

This section provides an additional 6 months of patent exclusivity for a previously approved drug that the FDA has approved for a new, “orphan” indication.  We support this section, but FDA should have the authority to revoke that extension if subsequent research indicates that the new indication (type of treatment) is not safe and effective enough to support approval. 

Subtitle L and M – These Medical Device sections have several provisions that concern us, because of the emphasis on shorter and smaller clinical trials, application of surrogate endpoints, and pressure on the FDA to use adaptive trials designs and Bayesian Statistics.  FDA scientists and statisticians should make those decisions, not Congress.  Our major concerns regarding these subtitles are specified in #6 and #7.

  1. Section 2221: Third-party Assessment

Under this section, makers of high-risk medical devices could pay a 3rd party to assess whether the company can accurately determine the safety and effectiveness of newly redesigned devices, instead of the companies submitting an application for the FDA to approve the newly revised device.  This is a bad idea for several reasons:

a.  FDA has testified that it would cost the agency more money and resources establishing and monitoring this program than they would spend actually reviewing these potentially dangerous high-risk devices.  At the same time, FDA would get no user fees to reimburse them for their work.  It therefore has no benefit to patients or taxpayers.

b.  3rd parties would be selected and paid by the companies.  The 3rd parties that have a track record of the most positive evaluations for the companies will have the most customers, creating an incentive for easy approvals rather than an incentive to protect the public health.

c.  Once a device manufacturer has been certified by a 3rd party, the manufacturer will be authorized to make changes to devices without first notifying or seeking approval from the FDA or any other outside entity, public or private. The bill would therefore create a new class of “certified” device manufacturers who would regulate themselves. The recent example of the Olympus endoscope that caused the deaths of patients after the company made design changes without FDA approval show that this is a dangerous idea.

  1. Section 2222: Medical Device Approvals

This section would lower the approval standards for high-risk medical devices, including those that can save lives (or could be fatal if they fail).  Under current law, the standards for high-risk medical devices are much lower than those for even the least important prescription drugs.  Most medical implants and high risk medical devices are currently reviewed through a 90-day process that does not require clinical trials on human beings.  Whereas drugs are tested in randomized clinical trials, even the highest risk medical devices are rarely tested on patients to see if they are better or worse than other treatments.

But the proposed law would lower current standards even more.  Even life-saving heart valves and stents could be approved on the basis of case studies of just one or two patients, or poorly conducted studies published in peer reviewed medical journals.

No peer-reviewed journals scrutinize the accuracy of the data submitted; they only review the interpretation of the data provided.  In contrast, the FDA has access to the complete trial protocols and datasets, can inspect clinical trial sites to monitor trial conduct, and often re-analyzes data to determine its accuracy.  Moreover, some peer-reviewed medical journals have a track record of publishing anything that is submitted. In addition to their questionable accuracy, peer reviewed studies would not necessarily include women, racial and ethnic minorities, people over 65, or children.

  1. Subtitle N, Health Software

This section defines “health software” and exempts it from FDA regulation. The proposed definition of “health software” includes Electronic Health and Medical Records (EHRs and EMRs) (under Section 2241(1)(C)) and software which guides treatment decisions by physicians (under Section 2241(1)(F)). This puts patients at risk, because if this software is inaccurate, patients can be harmed just as they would by other types of medical devices.

The bill states that the FDA could regain the ability to regulate software which guides treatment decisions by physicians (Section 2241(1)(F)) under narrow circumstances.  We disagree that health software should be exempt from FDA regulation.  However, if it is exempted in this bill, the process for regaining regulatory authority needs to be clearly described and should not be burdensome to the agency. In addition, EHRs and EMRs (defined under Section 2241(1)(C))  should be added to the type of software FDA could regain the ability to regulate.

  1. Section 3041:  Exempting Transparency When Companies Pay Physicians for Speeches or Other Activities

This loophole would create a gaping hole in the Physician Payment Sunshine Act, by exempting manufacturers from reporting speaker fees or gifts to doctors that are intended for “continuing medical education” purposes. These could include hefty fees and other valuable payments and gifts, such as expensive admission into medical conferences at lavish resorts. It would open another loophole by defining an existing exception for “educational materials that directly benefit patients” to include medical textbooks and journals. These very costly items are clearly gifts to doctors that they would otherwise have to pay for.

In conclusion, the proposed 21st Century Cures legislation includes provisions that we enthusiastically support, and we understand Members’ desire to move quickly.  However, many of the provisions in this 300-page legislation are based on complicated scientific issues and require much greater scrutiny by Congress and the public.  For example, the proposed increase in NIH funding deserves support, but there is no guarantee that an increase in authorized funding would translate into an increase in appropriated funds.  Similarly, the bill includes numerous unfunded mandates for the FDA, which would be more appropriately considered as part of future PDUFA and MDUFA legislation, so that funding and increased work load would be considered at the same time.

We are disappointed that our Coalition and most of our nonprofit member organizations have not been consulted as this legislation has been developed.  Most of our previous efforts to share the views of our tens of millions of constituents have been met with silence from majority staff and numerous minority staff as well. We strongly encourage you to revise the legislation so that it will have the support of the millions of patients, consumers, scientists, and health professionals represented by our organizations.


American Medical Women’s Association
Annie Appleseed Project
Association for Pelvic Organ Prolapse Support
Breast Cancer Action
Center for Medical Consumers
Jacobs Institute of Women’s Health
Mothers Against Medical Error
MRSA Survivors Network
National Center for Health Research
National Women’s Health Network
Our Bodies Ourselves
The TMJ Association
Center for Science and Democracy, Union of Concerned Scientists

The Patient, Consumer, and Public Health Coalition can be reached through Paul Brown at (202) 223-4000 or pb@center4research.org