Division of Dockets Management (HFA-305)
Food and Drug Administration
5630 Fishers Lane, Rm. 1061
Rockville, MD 20852

September 16, 2014

Comments of members of the Patient, Consumer, and Public Health Coalition
on Draft Guidance for Industry on Internet/Social Media Platforms:
Correcting Independent Third-Party Misinformation about Prescription Drugs and Medical Devices
Docket No. FDA-2014-D-0447

As members of the Patient, Consumer, and Public Health Coalition, we are writing to express our concerns about the draft guidance for “Correcting Independent Third-Party Misinformation about Prescription Drugs and Medical Devices.”

This draft guidance only applies to companies who “voluntarily choose” to correct misinformation that appears on the Internet or through social media platforms from third party entities. However, companies should be held responsible for the accuracy and balance of all information about their product that appears to be promotional, not just for sources they voluntarily choose to correct. Companies would have no incentive to correct information that praises or over-exaggerates the benefits of their product, so there would an imbalance in the type of information that gets corrected.

Due to the fact that this guidance is voluntary in nature and that there are no enforcement mechanisms in place, it will not do enough to protect individual patients or the public health more generally.  Only a strict requirement to correct misinformation would ensure that patients are not misled.

While we are sympathetic that it would be more work for companies to correct all online misinformation, we are certain that companies are aware of almost all information regarding their products that is either critical or promotional.  Information in blogs, patient Web sites, and other “independent” third party sources are often bought and paid for, directly or indirectly, by the companies whose products are being praised (or whose competitors’ products are being criticized).  Without any enforcement mechanism, it is impossible for patients, consumers and other stakeholders to determine the true source of the information, whether it is from an independent third party, and whether the information is accurate.  For example, some blogs and forums make it difficult or impossible to determine if the author is or isn’t associated with the company that makes the product.

To help minimize the misuse of social media and internet promotions, substantial penalties should be imposed on companies that pay for any promotional materials that are biased or inaccurate.

One example that illustrates this problem is Wikipedia. It is against the Wikipedia rules for companies to promote themselves, but the reality is very different.   Wikipedia is a major source of information to millions of people in America and around the world. This platform could allow someone to propagate a significant amount of information, including misinformation, to millions of consumers. Anyone, whether knowledgeable, biased, or not, is free to edit a Wikipedia article.  If the person editing an article were employed or paid by the company that made the product, directly or indirectly, Wikipedia administrators would not know that unless the individual doing the editing used an ISP associated with the company. As a result, Wikipedia articles about prescription drugs and medical devices vary greatly in balance and accuracy.

It is critical for FDA to ensure balance and accuracy on such platforms, because Wikipedia is the first source of information that appears on a Google search for many medical conditions, drugs, and other medical products.  Since Wikipedia has an army of volunteers whose job it is to enforce its rules aimed at reducing the use of their platform for promotional purposes, and since those rules are currently ineffective for ensuring the objectivity of information about medical products, FDA staff should reach out to Wikipedia officials to determine how the agency can provide information that would help Wikipedia determine how to improve its own efforts to ensure that information about medical products is “neutral” rather than promotional.

The draft guidance states that all corrective information provided by the drug or device companies should be “consistent with FDA-required labeling for the product.” We find this problematic because even if corrective information can be identical to FDA-approved labeling, it could also be incomplete. For example, a Web site can include exact wording about benefits but exclude or limit information about risks.  The FDA’s draft guidance needs to be more specific about the importance of providing complete labeling information in posted corrections to misinformation.

In addition, the draft guidance does not address the issue of information on off-label usage of medical products.  Patients could be harmed by misleading or incomplete information on the risks and benefits of off-label use of medical products.  It is essential that the FDA stipulate that companies must also identify when information refers to indications not approved by the FDA and inform consumers that the accuracy of such statements has not been reviewed by the FDA.

The draft guidance recommends providing a link that goes directly to FDA-required labeling. Although we think providing a link is a great idea, information about risks should also appear on the actual Web sites and forums. One click away is one click too many. If the information about benefits doesn’t require a click, the information about risks shouldn’t require a click either. Unlike TV, radio, and magazine ads where every piece of information costs a lot of money to include, it is much easier and cheaper to include comprehensive risk information on the Internet.

A major shortcoming of the guidance is that there are no requirements for how speedily a company must correct misinformation. In the world of social media and “viral” marketing, it may only take a few hours for content to go live and reach the targeted audience. If there is no time frame in which companies must correct the misinformation, then on many platforms like Twitter and Facebook, a correction may be ineffective after a significant amount of time has gone by.

In conclusion, the Internet and social media are often the first source of information that health professionals and consumers use to find out about risks and benefits of medical products.  This information has the potential to influence consumer behavior and physician treatment decisions.  The FDA needs to make sure that the information available on the Internet is as accurate and balanced as possible, and should not rely on companies who make the medical products to voluntarily correct flattering or promotional material about the products they are selling. FDA should require companies to correct this information to the greatest extent possible in order to ensure that consumers are not influenced by misinformation that may harm their health.

Annie Appleseed Project
Breast Cancer Action
Center for Medical Consumers
Connecticut Center for Patient Safety
MISSD
National Center for Health Research
Our Bodies Ourselves
The TMJ Association
WARS
WoodyMatters

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

Division of Dockets Management (HFA-305)
Food and Drug Administration
5630 Fishers Lane, Rm. 1061
Rockville, MD 20852

August 25, 2014

Comments of Members of the Patient, Consumer, and Public Health Coalition
on the Draft Guidance
Medical Device Data Systems, Medical Image Storage Devices, and Medical Image Communication Devices
[Docket No. FDA-2014-D-0798]

As Members of the Patient, Consumer, and Public Health Coalition, we are writing to express our opposition to the draft guidance Medical Device Data Systems, Medical Image Storage Devices, and Medical Image Communication Devices. With this draft guidance, the FDA is notifying manufacturers and others that it “does not intend to enforce compliance with regulatory controls that apply to” medical device data systems (MDDS), medical image storage devices, and medical image communications devices.  The FDA has stated it is using its enforcement discretion on these devices because of “the low risk they pose to patients and the importance they play in advancing digital health.” We strongly disagree.

We examined the MAUDE adverse events database for these devices and found 224 adverse events reports; it is widely known that MAUDE drastically undercounts adverse events. MDDS devices (product code OUG) had 66 adverse events reported to MAUDE including four deaths and ten injuries associated with the devices. One of the deaths involved an “un-viewable transmission” that was a care alert.1

One MAUDE report stated, “Death from the delay in diagnosing and treating sepsis was narrowly avoided.”2 Another MAUDE report stated that a typo in an Electronic Health Record (EHR) (two apostrophes on a name instead of one) led to an injury of a critically ill patient because the EHR could not be accessed. The report states, “The vendor’s device is defective…it failed to warn of the error. These MDDS devices need tighter regulation, surveillance and safety”3 (emphasis added).

The MAUDE database shows 65 adverse events for medical image storage devices (product code LMB) and 93 adverse events for medical imaging communication devices (product codes NGE and LMD).  A report on Siemens’ Soarian/Invision EHR raised concerns about an allergy alert falling through the cracks in the electronic health records.  The MAUDE report states, “We are concerned that if such a basic error is allowed to go unrecognized by these supposedly safe devices, how safe are they exactly”? (emphasis added).4

In 2011, the FDA down-classified MDDS from Class III (high-risk) to Class I (low-risk).  The agency stated, “Since then, FDA gained additional experience with these types of technologies and has determined that these devices pose a low risk to the public.”5 However, all 66 of MAUDE adverse events for the MDDS (product code OUG) were from 2011- July 2014, which seems to contradict the FDA’s claim that these devices now pose a low risk.

The draft guidance states that “MDDS are not intended to be used in connections with active patient monitoring.”  How will FDA enforce the prohibition on using MDDS for active patient monitoring?

By not enforcing compliance with regulatory controls, basic information will not be collected by the FDA “including registration and listing, premarket review, postmarket reporting and quality system regulation for manufacturers of these types of devices.”6 This would make it much more difficult to recall a defective product such as the Class II recall in 2012 for the MDDS device (CareFusion 209 Inc.) that affected 1,676 devices, recalled  because the devices “may continue to display the previous patient’s exams.”7

The FDA’s core mission is to protect the public health by ensuring the safety and effectiveness of medical products. If the FDA uses its enforcement discretion to ignore regulations on devices that can seriously harm patients when they don’t work well, it will put many patients and the public health at risk.

Annie Appleseed Project
Breast Cancer Action
Connecticut Center for Patient Safety
National Center for Health Research
National Organization for Women
The TMJ Association
WARS
WoodyMatters

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

 

September 9, 2014

The Honorable Barbara Mikulski
Chairwoman
Committee on Appropriations
United States Senate
S128, US Capitol
Washington, DC 20510

The Honorable Richard Shelby
Ranking Member
Committee on Appropriations
United States Senate
S-146A US Capitol
Washington DC 20510

Dear Chairwoman Mikulski and Ranking Member Shelby:

In November 2013, the Food and Drug Administration (FDA) proposed to revise its regulations to allow generic drug manufacturers to initiate safety updates to their products’ labeling.8 We strongly support the FDA’s proposal.

Generic manufacturers currently are barred from providing new warning information, except in response to a brand-name update or FDA order.  Yet most prescription drugs sold in the United States are generic versions, and the brand-name manufacturer often stops selling the drug after generic versions come on the market.

Allowing the generic manufacturers to initiate safety updates, as brand-name companies have done for 30 years, is essential to patients and consumers, as promptly updated warnings can provide informed consent to patients and physicians and prevent serious harm to patients.

Recently, the House Committee on Appropriations included a few sentences in its report of the Agriculture, Rural Development, Food and Drug Administration, and Related Agencies Appropriations Bill for fiscal year 2015 that would unnecessarily delay the FDA’s ability to finalize the proposed rule and leave patients and consumers exposed to the current inadequate safegurds.

Patients and consumers deserve up-to-date information about the prescription drugs they use, including the most up-to-date safety warnings.  Allowing generic drug manufacturers the flexibility to update safety labeling as soon as they become aware of new information is important to protect the health of all Americans and maintain the public’s trust in generic drugs.  The FDA’s proposal deserves the strong support of Congress and all those who care about public health in the United States.

We strongly oppose the inclusion of the House Language and ask for your support in making sure that it is not included in any final appropriations report for the Food and Drug Administration, or any other legislation.

Thank you for your consideration.

Alliance for Justice
Alpha-1 Foundation
American Autoimmune Related Diseases Association
American Medical Student Association
American Medical Women’s Association
Annie Appleseed Project
Brain Injury Association of America
Breast Cancer Action
Center for Justice & Democracy at New York Law School
Center for Medical Consumers
Center for Science and Democracy at the Union of Concerned Scientists
Connecticut Center for Patient Safety
Consumers Union
COPD Foundation
Jacobs Institute of Women’s Health
Lupus Foundation of America
Mothers Against Medical Error
National Center for Health Research
National Consumers League
National Eczema Association
National Latina Institute for Reproductive Health
National Physicians Alliance
National Women’s Health Network
New Yorkers for Patient & Family Empowerment
Our Bodies Ourselves
Prevent Blindness America
Public Citizen
Public Justice
Reproductive Health Technologies Project
Sjogren’s Syndrome Foundation
The TMJ Association
U.S. PIRG
WARS
WoodyMatters

The organizations listed above can be reached through Paul Brown at (202) 223-4000 or at pb@center4research.org

Division of Dockets Management
Food and Drug Administration
5630 Fishers Lane, Room 1061 (HFA-305)
Rockville, Maryland 20852

August 25, 2014

Comments of the Patient, Consumer and Public Health Coalition
on the Draft Guidance for Industry on
“Distributing Scientific and Medical Publications on Risk Information for Approved Prescription Drugs and Biological Products—Recommended Practices”
Docket No. FDA-2014-D-0758

As members of the Patient, Consumer and Public Health Coalition, we strongly urge the Food and Drug Administration (FDA) to withdraw its draft guidance proposing to allow pharmaceutical firms to distribute to health care providers and facilities scientific medical literature suggesting that the risk information for prescription drugs and biological products are less than what is stated in the FDA-approved product labeling. The guidance has the potential to cause confusion and greatly harm patients.  It would undermine the public health mission of the FDA by allowing companies to provide potentially invalid and misleading information that patients and their physicians would use as the basis for medical decisions.

The guidance would allow the distribution of risk information prior to FDA approval of formal changes to label information.  While proposed changes to FDA-approved labels that involve removal or mitigation of previously stated risk information must be reviewed and approved by the FDA in accordance with existing regulatory requirements, the publications that would be distributed in accordance with this proposed guidance would not be reviewed by the FDA.  Thus, there will be no safeguards to ensure that the “new risk information” is unbiased or accurate.

The draft guidance states that it “is not intended to apply to information about a newly identified risk (not previously included in the approved labeling) or new information that indicates that a risk already identified in approved labeling is more serious [italics ours] than is reflected in that labeling.”  The guidance states that, “the term new risk information refers to information that becomes available after a drug is marketed that rebuts or mitigates information about a risk already identified in the approved labeling.”   This limited definition of “new risk information” essentially facilitates more rapid communication of reduced risk alone, but neglects greater risk. Moreover, there would be no safeguards to ensure that the “new risk information” is unbiased or accurate.

The FDA recommends that the scientific and medical data should be from independent, peer-reviewed journals, and be “at least as persuasive as the data sources that underlie the existing risk assessment…as reflected in approved labeling.”  However, it is widely recognized that peer-reviewed scientific journals vary significantly in their data requirements and review standards for publication.  Moreover, many peer reviewed articles are ghostwritten by industry staff and consultants.9 There is no assurance that the peer-reviewed journal processes would approach the comprehensiveness and scrutiny of an FDA pre-market review. Moreover, journals of varying standards would be entrusted to review critical risk data that could have dire health implications for patients.  The FDA acknowledges the potential for harm, stating that “if the new information is unreliable or presented without the appropriate context, it could influence prescribing decisions or patient monitoring in a way that could harm patients.”   Yet, the FDA guidance would allow such biased information to undermine the integrity of risk information provided to physicians (and indirectly, to patients).

The FDA guidance suggests a cover sheet to accompany such literature, which would include several pertinent statements, including a reminder that the FDA has not reviewed the data, and disclosing any financial interests or affiliations between the study authors and the company. This cover sheet would not be sufficient to counterbalance biased or questionable information in the articles.  Moreover, guidance documents are non-binding, and no enforcement strategies have been outlined. Companies would therefore be under no obligation to comply with these suggested restrictions.

Obviously, companies would not be likely to distribute scientific or medical articles that indicate an increased risk of their own products, but they might want to distribute scientific or medical articles that indicate an increased risk of their competitors’ products.  Such information could certainly be biased or inaccurate, but not more so than the information provided by companies regarding their own products. So, why would the FDA allow one type of communication and not the other?  We believe distribution of either type of risk information by drug company reps is unacceptable.

In addition to the problematic public health implications of this guidance, we strongly question its scientific rationale.  The draft guidance notes the value of post-market information, stating that premarket risk information may be limited in assessing a drug’s safety profile “by the nature of the supporting data and the size of the population exposed.”  However, if a rare safety signal is detected in small pre-market studies, finding a reduced risk in a larger post-market study would be unexpected, and would deserve careful unbiased scrutiny from FDA scientists before that information could be used to influence physicians’ prescribing habits.  Moreover, a larger or more generalizable post-market study that confirms or identifies rare safety events would be much more likely.  Yet this guidance intentionally does not address this situation.

In summary, this guidance is misguided and dangerous.  It would undermine the already limited efficacy of risk information provided in FDA-approved labels by allowing the distribution of competing risk information not subject to the same scientific rigor and neutrality which are the whole rationale for the existence of the FDA review process.  We strongly urge the FDA to withdraw this poorly conceived guidance, which would allow potentially unsubstantiated safety information to be communicated without the safeguards patients need and the public health deserves.

American Medical Student Association
American Medical Women’s Association
Annie Appleseed Project
Breast Cancer Action
Center for Medical Consumers
Community Catalyst
Connecticut Center for Patient Safety
Consumer Reports
Jacobs Institute of Women’s Health
MISSD
National Center for Health Research
National Organization for Women
National Women’s Health Network
Our Bodies Ourselves
POGO
The TMJ Association
WARS
WomenHeart: The National Coalition for Women with Heart Disease
WoodyMatters

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

September 11th, 2014

 

My name is Dr. Laurén Doamekpor, and I am a senior fellow at the National Center for Health Research. Our research center scrutinizes scientific and medical data and provides objective health information to patients, providers and policy makers. We do not accept funding from drug companies, and therefore I have no conflicts of interest.

We all know that obesity comes with many health risks, and millions of Americans would benefit from safe and effective treatment options.  After a careful review of the data, I am sure that many of you share our skepticism about whether Liraglutide meets the standards of safety and efficacy that patients and consumers deserve.

1) Like most weight loss strategies, this drug helps patients lose weight during the first year.  But obesity is usually a chronic condition and any potential treatment should be studied for much longer than 1 year.  We need more than 2-year data to know if the drug is effective and safe.

The data from the largest trial (trial 1839) show that patients in the Liraglutide group were almost 3 times as likely to experience an adverse event compared to the placebo group, some of them serious. When the weight management data were pooled, patients on Liraglutide were more likely to experience gallbladder disorders and pancreatic conditions. Victoza when used for diabetes, has been found to cause pancreatitis in post-market studies.  Now that we know these risks, we need to be very concerned about them with Liraglutide as well, since it has the same active ingredient.  At the very least, longer term studies are needed BEFORE Liraglutide is approved and BEFORE patients are buying it.

2) We question whether this drug will work effectively and safely in people of color. Pooled data from the 4 phase 3 trials showed that Black patients made up only 11% of the trial samples and Hispanic patients made up only 10%. The sponsor states that the U.S. trial population reflects the racial and ethnic distribution in the U.S. but it does NOT reflect the prevalence of obesity in these racial and ethnic groups.

Black adults, particularly Black women, are more likely to be overweight and obese than any other racial group in the U.S. They are also more likely to have sleep apnea and type 2 diabetes. Because the sponsor did not conduct any subgroup analyses, despite FDA guidance to do so, we don’t know about the safety or efficacy for Black men or women based on these data.

If the sponsor wants this drug approved for all adults, not just White adults, it needs to be analyzed separately for a reasonable number of Black and Hispanic adults.

We urge you to vote that the benefit-risk assessment is NOT favorable and does NOT support approval because of the lack of data on long-term efficacy and safety AND the lack of meaningful data on safety and efficacy for people of color.

 

 

Written by Laurén A. Doamekpor

September 9, 2014

Good afternoon. My name is Anna Mazzucco and I’m speaking on behalf of the National Center for Health Research. Our non-profit research center assesses scientific and medical data and provides objective health information to patients, providers and policy makers. Our organization does not accept funding from drug companies, and therefore I have no conflicts of interest.

We know that hypertension is a condition that affects millions of Americans. One in 3 adults has high blood pressure and is at risk for other serious health conditions, such as heart disease and death.

Our medical and scientific experts have carefully reviewed the data provided to you by the FDA and we want to share our concerns:

Data from the pivotal trial showed that the trial’s primary and key secondary endpoints were met. Patients on the highest-dose of the FDC (20/320 mg) had very small but statistically greater mean reductions in DBP and SBP as compared with the highest approved dose of the monotherapy drugs.  However, patients in this trial were only treated for 8-weeks. Most hypertension patients require medication for years if not decades.  As all of you know, this trial should have been much longer.

We share the FDA’s reservations about the clinical relevance of the small reductions in blood pressure. We question whether approving this combination drug will make a difference in patients’ health.

Is a small improvement worth the risk of adding a second drug?  With only 8 weeks of data, it is impossible to say with any conviction that this combination product is safe.  That means it is impossible to say whether the tiny benefit outweighs the unknown risks.

And since there is so little benefit, we are especially concerned about the lack of diversity in the efficacy and safety pivotal trials. Most patients were White and younger than 65 years. Blacks are more likely to have high blood pressure compared to any other racial or ethnic group. Adults over the age of 60 are much more likely to develop hypertension as well. But only about 10% of the patients in the efficacy trial were Black and only 9% of both pivotal trial samples were over 65.

This is not an issue of political correctness.  Older adults metabolize drugs differently than younger adults. In some cases, such as beta blockers, we know that Blacks tend to metabolize blood pressure medications differently than Whites.

Fortunately, the sponsor conducted subgroup analyses in both trials. The results showed racial differences.  There was no difference in blood pressure reduction for Black patients on the combined drug FDC 20/320 compared to patients in the monotherapy 40 mg arm.

Those results indicate that FDC 20/320 does not work for Black patients and should not be approved for them.  However, with the small number of Blacks in the different dosage groups, it is impossible to conclude with any confidence that FDC at any dosage is more effective for Blacks than the monotherapy drug alone.  If the company wants approval of its drug for non-white patients, they need to study a large number of them to see if it is effective for a generalizable population.

Subgroup analyses in the safety pivotal trial exposed important differences. Although there was a generally low incidence of adverse events across the unfortunately short-term study, patients over the age of 65 in either the experimental group or the monotherapy group were more likely to have bradycardia than younger patients.   That’s important information for the label for the  monotherapy drug, which is already on the market, as well as the combination drug if it is approved.

In summary:

  1. The sponsor has not proven that their drug is safe for patients using it for more than 8 weeks.  That is not an acceptable study for a blood pressure medication that would be taken for years.
  2. The sponsor has not proven this their drug is effective for non-white populations, compared to monotherapy, but preliminary data indicate that it is not effective at the 20/320 dose.

Hypertension is a major cause of death.  If FDC is approved on the basis of such weak data, it could potentially harm millions of patients.  It is not enough to require post-market studies to answer questions that are essential to answer BEFORE this drug is approved.

Please request longer term data with larger numbers of minority patients BEFORE approving this combination drug.

September 3, 2014

Good afternoon. My name is Dr. Laurén Doamekpor, and I am a senior fellow at the National Center for Health Research. Thank you for the opportunity to speak today. Our non-profit research center assesses scientific and medical data and provides objective health information to patients, providers and policy makers. We have great respect for the FDA, which is why our center’s president is on the Board of Directors of 2 nonprofit organizations focused on providing additional resources to the FDA: the Alliance for a Stronger FDA and the Congressionally mandated Reagan-Udall Foundation. We do not accept funding from drug companies therefore I have no conflicts to disclose.

We are all aware of the important role that OTC antiseptics play in reducing the risk of infection, particularly in the healthcare setting. That is why it is crucial to ensure that the ingredients in these products are as safe and effective as possible.

In our review of the FDA’s proposed safety framework, we were encouraged to see that many of the studies that the FDA proposes to support a GRAS determination for an OTC antiseptic active focus on the right questions. We agree that it is important that studies address the degree of human absorption, metabolic rates and carcinogenic effects. However, considering that many healthcare antiseptics are used more than once, and in many cases for extended periods of time, it is important that studies be conducted for long enough periods of time to establish the real world effect of these ingredients.

Based on the FDA’s proposed framework, the summary of the available data for the healthcare active ingredients shows that there are many unanswered questions about the safety of the healthcare antiseptic drug products. In fact, for some of the ingredients, close to nothing is known. This concerns us, and I’m sure it concerns you as well.

For example, even though alcohol is commonly used in antiseptic products in the healthcare setting, but only some data are available about human absorption. In some cases, such as benzalkonium chloride, the only data available are on bacterial resistance, not safety issues.

Hospital-acquired infections are a major killer in the U.S. today.  Without more data, patients are at risk for infections, adverse reactions, and death.

We are particularly concerned about pregnant healthcare workers who may be exposed to some of these antiseptic ingredients several times during their pregnancy. Since many of these ingredients lack important safety data, there must be additional warnings provided on these products for women who are pregnant or breastfeeding.

As you continue your discussion today, please keep these unanswered questions in mind.  Patients’ health and safety should be at the forefront of this meeting.

The National Center for Health Research explains why drugs have to be tested on all kinds of people to know who they work for and who can be harmed by them. We’re quoted in MedPage Today, and blogs by the Wall Street Journal and The Scientist.

 

FDA is Chastised Over its ‘Action Plan’ to Diversify Clinical Trial Participation

By Ed Silverman, The Wall Street Journal

August 28, 2014

In response to a law passed two years ago, the FDA was directed to assess the extent to which women and minorities are represented in clinical trials and also devise a plan to bolster their participation. The requirement was made in response to concerns that drugs and devices may often be used by subsets of the population on whom the products were not actually tested.

Well, the FDA released its plan the other day and it was met with what could best be described as faint praise. In particular, a pair of consumer advocacy groups says the biggest issue is that the so-called Action Plan lacks the sort of teeth needed to generate real change. They also complain the plan fails to require drug and device makers to contain specific demographic information in product labeling.

They acknowledged the plan does contain several constructive steps, such as working with drug and device makers to revise product applications with enhanced information on “demographic subgroups;” strengthening FDA reviewer training so the need for demographic data is communicated; improving FDA systems for collecting and analyzing such data; and updating or finalizing guidance for industry.

“The action plan has a lot of good things,” Diana Zuckerman, the president of the National Center for Health Research, tells us. “The problem is there is no incentive for industry to recruit more diverse groups of patients. As long as they continue to test mostly on white men under 65 [years old] and get drugs and devices approved, then they have no incentives” to diversify the pool of trial participants.

What does she suggest? The FDA ought to consider not approving drugs and devices for use in people on whom these products were not tested. As an example, if a drug is tested predominantly on men, then the agency should not endorse widespread use for women. “They need to put some muscle behind their actions. I think if FDA did this,” she says, “then the companies would find they’re able to miraculously find they can recruit all those groups.”

Read the original article here.

Surgery Studies Rarely Use Females

An analysis of papers published in several surgical journals reveals an overwhelming reliance on male subjects and male-derived cells.

 

By Kerry Grens, The Scientist

August 28, 2014

Sex biases are evidenced in many areas of science—from clinical trials in humans to basic neuroscience studies on animals. Often, male subjects are overrepresented, compromising the generalizability of findings. In a study published in the September issue of Surgery, researchers from Northwestern University analyzed more than 2,300 papers from five surgical journals, finding an overwhelming skew toward investigations involving male-only subjects and cells derived from males.

“Women make up half the population, but in surgical literature, 80 percent of the studies only use males,” Northwestern Medicine vascular surgeon Melina Kibbe, who led the study, said in a press release.

The studies Kibbe and her colleagues reviewed were published in the Annals of Surgery, the American Journal of SurgeryJAMA Surgery, the Journal of Surgical Research, and Surgery from 2011 to 2012. About a quarter of the studies involved animals or cells. Just 3 percent of the total reported using both male and female subjects or cells, while another 22 percent did not state the sex.

According to the release, “editors of the five major surgical journals reviewed in this study have responded to this finding and will now require authors to state the sex of animals and cells used in their studies. If they use only one sex in their studies, they will be asked to justify why.”

Although sex disparities in clinical trials have received considerable attention, such human studies still suffer from unsatisfactory diversity. Last week, for instance, the US Food and Drug Administration (FDA) released an action plan to address the need for more women and minorities in clinical trials. The Wall Street Journal’s Pharmalot blog pointed out that the plan was met with “faint praise,” lacking “the sort of teeth needed to generate real change.”

Speaking with MedPage Today, Diana Zuckerman, the president of the National Center for Health Research, said: “As long as the FDA is going to approve these products for everyone, when they haven’t been studied on everyone, then the [pharmaceutical] companies really have no incentive to improve.”

Read the original article here.

August 20, 2014

Division of Dockets Management (HFA-305)
Food and Drug Administration
5630 Fishers Lane, Rm. 1061
Rockville, MD 20852

Comments of Members of the Patient, Consumer, and Public Health Coalition
on the Proposed Order
Microbiology Devices; Reclassification of Influenza Virus Antigen Detection Test Systems
Intended for Use Directly With Clinical Specimens
[Docket No. FDA-2014-N-0440]

Members of the Patient, Consumer, and Public Health Coalition strongly support the up-classification of influenza detection devices. We support moving the devices from class I to class II with special controls and into a new device classification regulation (from 21 CFR 866.3330 to 21 CFR 866.3328).  We agree with the FDA that “the accuracy of these devices has serious public health implications,” since influenza can cause serious illness and death.10

Many of the rapid influenza antigen detection tests or RIDTs (also referred to as antigen tests) that were cleared since 1998 have had performance problems (good specificity but low sensitivity).11 The 2009 flu pandemic underscored that RIDTs “performed poorly resulting in misdiagnosed cases.”12

On June 13, 2013, the Microbiology Advisory Panel met to discuss performance problems with RIDT systems. The panel noted that “poor sensitivity of RIDTs has always been a concern,”13 and they raised concerns that influenza viruses mutate quickly.  Fast changing viruses “may cause the functional components of influenza diagnostic devices not to recognize current influenza strains,” which will lead the devices to provide inaccurate results.14

Panel members indicated that putting RIDTs into Class II with special controls was needed to mitigate the risks of false positive and false negative results.  We strongly agree.

In the past, FDA has cleared these less-than-effective RIDT devices as class I 510(k) devices. This allowed the devices to be used as predicates for new 510(k) submissions, which “promotes further clearance of devices that do not meet the needed performance for detection and management of infection by novel strains of influenza.”15  Reclassifying RIDTs as class II will better ensure that ineffective devices are no longer cleared on an ineffective class I RIDT predicate. Devices that were cleared as class I RIDTs will have to meet the class II special controls to remain on the market, which will better protect patients and public health.

We agree with FDA’s proposed order that RIDTs regulated under 21 CFR 866.3330 be reclassified into Class II with special controls under the new device name “influenza virus antigen detection tests system”(21 CFR 866.3328).  Section 866.3328 specifically states, “Because influenza is highly contagious and may lead to an acute respiratory tract infection causing severe illness and even death, the accuracy of these devices has serious public health implications.”16 The regulation also lists precise special controls for these devices including sensitivity and specificity performance characteristics.

The early diagnosis of influenza can reduce the inappropriate use of antibiotics.  In contrast, the failure of the device to perform accurately could harm patients. For example, a false negative could result in a dangerous delay in treatment, or could result in spreading the flu in families and communities as well as vulnerable settings such as hospitals, retirement communities, and nursing homes. A false positive could lead to unnecessarily isolating a patient or a delay in treating respiratory infections caused by something else besides the flu.

Conclusions

Due to the widespread use of RIDTs—and their current lack of accuracy—we strongly support the FDA’s proposed order to up-classify the devices from class I to class II with special controls.  More stringent requirements for influenza diagnostic devices would assist health care professionals in accurately diagnosing patients, and help public health officials better respond to influenza outbreaks. Because flu viruses can make people severely ill or lead to death, RIDTs must be as accurate as possible, and up-classification with specific special controls is urgently needed to protect patients and the public health.

American Medical Women’s Association
Annie Appleseed Project
Center for Medical Consumers
Connecticut Center for Patient Safety
National Center for Health Research
National Consumers League
National Organization for Women
National Women’s Health Network
POGO
Public Citizen
WARS
WoodyMatters

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

By Diana Zuckerman, Ph.D.

The media frenzy surrounding the Ebola crisis in West Africa shows that many journalists don’t understand that an experimental drug is just that – a scientific experiment. It is not a “breakthrough” drug or a “cutting-edge treatment” or a prize to be envied, unless or until it is proven to be safer and more effective than nothing.

Ebola is a deadly disease, but it doesn’t kill 100% of those who are diagnosed. Experts estimate that this Ebola strain kills 60% of patients. That’s horrific, but not high enough to say with certainty that a person who took the experimental drug and survives has been saved by the drug – as Sanjay Gupta announced on CNN.

The CDC points out that some Ebola patients recover with no treatment other than “supportive care.” We don’t yet know if the experimental drug for Ebola, ZMapp, helps patients more than supportive care. Nevertheless, the hype keeps growing and pressure on the FDA is mounting to make the treatment more available. The FDA already responded to that pressure by making another Ebola drug, TKM-Ebola, more available, even though it is also not proven safe or effective.

In addition to the “we need new drugs faster” mantra in the U.S. — which is almost as strong for every other new drug as it is for Ebola drugs — one of the messages coming from overseas is that the U.S. is hogging this miracle drug for its own citizens. USA Today reports that, “Two Americans with Ebola received at least half of the world’s supply of a drug that might be able to change the course of the deadly virus. Some people are asking how to allocate additional doses of this drug and whether it was ethical to give those drugs to American missionaries when they weren’t available to West Africans suffering from or fighting the outbreak…. Anthony Kamara, a 27-year-old man riding a bicycle in Freetown, Sierra Leone, said ‘Americans are very selfish. They only care about the lives of themselves and no one else.’”

Medical ethicists point out that it is appropriate to give limited drug supplies to medical missionaries such as Nancy Writebol and Kent Brantly, because as first responders they got sick caring for Ebola patients. And, the FDA already has a humanitarian exemption that allows patients’ access to experimental drugs when necessary, if the drug company agrees to it. So, rushing FDA approval for ZMapp or other Ebola drugs is not necessary and we can all feel good that the two patients seem to be doing well so far.

It is discouraging to see so many journalists and “talking heads” missing the point: we don’t know yet if ZMapp, or any other Ebola drugs in development, will save lives or cost lives. We don’t know if some of these drugs might work on patients at an early stage of the disease but harm them at a later stage. Science can eventually tell us, and this epidemic may be a good time to test experimental drugs, but science takes time. It makes sense to give patients an informed choice to face the risks of an experimental drug, if that is possible, but that doesn’t mean that it is ethical to distribute an unproven drug to everyone.

Urgent situations show us how important good science is, but good science takes time. AIDS activists have learned those lessons and are now recommending FDA be cautious before approving unproven new drugs: “AIDS Activist Takes Up New Fight: Defending FDA,” AP, August 11, 2014.

Meanwhile, let’s celebrate the efforts of scientists to cure Ebola and use the teachable moment to explain why research is necessary and why it is important to do it well.

——

Read the article on AAAS’s “Sci on the Fly” blog here.