June 13, 2022.

National Center for Health Research’s Comments on Diversity Plans to Improve Enrollment of Participants From Underrepresented Racial and Ethnic Populations in Clinical Trials [FDA-2021-D-0789]

We are writing to express our views on the Food and Drug Administration’s (FDA) draft guidance to provide recommendations to sponsors developing medical products on the approach for developing a plan to enroll representative numbers of participants from underrepresented racial and ethnic populations.

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

We strongly support the proposed recommendations which provide specific, actionable guidance for sponsors to develop a meaningful Race and Ethnicity Diversity Plan. In particular, we appreciate the proposed recommendation for sponsors to clearly define and justify enrollment goals for underrepresented racial and ethnic minority populations. Most important, representation in a trial must be adequate to conduct appropriate subgroup analyses on efficacy and safety. For example, if a minority group is 20% of the patient population but there are only 100 patients in the entire study, 20 patients would be 20% but would not be sufficient to determine safety or efficacy for that group.

It is thus encouraging that the draft proposal recommends that sponsors provide any available evidence describing disparities in health outcomes related to the drug or therapy, but acknowledges that the lack of this evidence should not be grounds to ignore the importance of diversity.  For too long, many clinically meaningful disparities in the efficacy of drugs or therapies in minority populations have been hidden by a lack of data. Thus, it is crucial to ensure that sponsors describe existing research on similarities and differences in how the disease or condition under study is experienced by racial and ethnic minorities, and identify potential gaps in existing data.

The goal is for the inclusion of these recommendations to improve the accountability of sponsors to make real and sustainable improvements in the representation of minorities in trials. However, to truly hold sponsors accountable, this draft proposal should go further by providing meaningful incentives for sponsors to follow the recommendations outlined. The most meaningful incentive within current law would be that FDA make it clear that the agency will not approve medical products for all populations if the product was not adequately tested for safety and efficacy on sufficient numbers of patients representing major demographic subgroups.

National Center for Health Research can be reached at info@center4research.org or at (202) 223-4000.

July 29, 2022

We are writing to express our views on the AHRQ Draft Comparative Effectiveness Review comparing Partial Breast Irradiation (PBI) to Whole Breast Irradiation (WBI) as a treatment for early-stage breast cancer.

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

We agree with the AHRQ review that clinical trials provide sufficient evidence that PBI is a valuable treatment option for select patients with early-stage breast cancer. Patient outcomes for several types of PBI did not differ significantly from WBI patients in terms of ipsilateral breast recurrence (IBR), overall survival, and cancer-free survival at 5 and 10 years. However, IORT PBI patients did have higher levels of recurrence (IBR) than WBI patients, despite no difference in overall survival or cancer-free survival.  Overall, PBI patients have fewer acute adverse effects, lower transportation costs and days away from work, and fewer financial strains, making it a more convenient therapy option compared to WBI.  

However, there are numerous types of PBI, and the data are not adequate on the effectiveness of each one of them compared to WBI.  In addition, we agree with the AHRQ review that there is currently insufficient data to draw conclusions about the risks and benefits of different types of PBI compared to each other or to WBI for women who are diverse in terms of patient, tumor, and treatment characteristics. Outcomes at 15 and 20 years are also important to evaluate. For these reasons, more research is necessary to provide the most useful information to patients considering breast irradiation.

For more information, please contact Dr. Diana Zuckerman at dz@center4research.org. 

Emily Alpert Reyes, Los Angeles Times, June 23, 2022

In Rochester, N.Y., Diane Coleman has relied on a machine to help her stay alive, but she worries that it might be slowly undermining her health.

Her ventilator was among millions of breathing devices that Philips Respironics recalled last summer over safety concerns about numerous models of its ventilators, BiPAP and CPAP machines.

The reason: Polyester-based polyurethane foam used to muffle noise in those machines could degrade, giving off chemical gases and bits of black debris that could be swallowed or inhaled.

The possible risks: headaches, dizziness, nausea, irritated eyes and airways, and “toxic or cancer-causing effects,” according to federal regulators. The Food and Drug Administration put the recall in its most serious category, involving “a reasonable probability” that a product “will cause serious adverse health consequences or death.”

Yet a year later, many patients are still awaiting replacements — and some are using the recalled machines despite those possible risks.

Coleman said her machine underwent some initial repairs, but she is seeking a new one after federal regulators sought more safety testing of the replacement foam used for such fixes. The 68-year-old, who is president and chief executive of the disability rights group Not Dead Yet, has a form of muscular dystrophy and uses her ventilator roughly 22 hours each day.

She is nervous about how it could affect her, but “it’s not like I can stop using it.”

[….]

The devices are commonly used to treat sleep apnea, a disorder in which breathing is repeatedly interrupted during sleep, which can increase the risk of heart problems and leave people dangerously drowsy during the day. The FDA has advised patients who use the recalled CPAP or BiPAP machines to talk to their doctors about whether to stop.

Tom Wilson, who administers a Facebook support group for CPAP users affected by the recall, said he has read comments from group members who say they haven’t had any communication with Philips despite registering their devices with the company as much as a year ago. Some have paid out of pocket to get other devices.

[….]

“They’ve botched the whole thing,” said Dena Young, senior counsel at Berger Montague, who said that most of the people represented by her firm had not gotten a replacement or repair. As they wait, “some of them are still using the Philips because they don’t have a choice.”

Federal investigators have also taken interest: In April, Philips said the U.S. Department of Justice had subpoenaed the company in regards to events leading to the recall.

Consumer safety advocates argue that the halting process underscores the shortcomings of the recall system, which relies heavily on private companies to inform consumers and take action.

“It isn’t actually easy for the FDA to take products off the market,” said Diana Zuckerman, president of the National Center for Health Research, a nonprofit research center that has raised concerns about the safety of medical products. “It should be a lot easier than it is.”

But the actions that the FDA has taken so far in the Philips recall also show that the agency “has more power in recalls than they usually use,” Zuckerman said.

The FDA’s Center for Devices and Radiological Health told Philips last month that it was seeking to order the company to turn in a plan that could include not only repairing and replacing the recalled devices, but also providing refunds. In a November report, an FDA investigator found that Philips had failed to start taking appropriate action years earlier when the company first became aware the foam could be breaking down. Emails showed that the company was aware of “foam degradation issues” as early as October 2015, the FDA investigator found.

Within three years, more emails indicated that Philips had gotten more complaints about crumbling foam in ventilators and said that testing had confirmed that it broke down in high heat and high humidity, but the firm “made the decision not to change the design,” according to the FDA report in November. The FDA investigator noted that dating to 2008, Philips had gotten more than 222,000 consumer complaints that included keywords such as “contaminants, particles, foam, debris, airway, particulate, airpath and black.”

[….]

This year, the FDA found that Philips’ efforts to alert patients were insufficient, concluding that many patients were probably still unaware of the health risks nine months after the recall had begun. In March, it ordered the company to notify health professionals, device distributors and users of the recalled machines after estimating that only 50% of patients and consumers who had gotten recalled CPAPs and BiPAPs within the last five years had registered with the company for a replacement.

[….]

In Philadelphia, Meghann Luczkowski likewise worried about what would happen if Miles, her 8-year-old son, were switched to a different ventilator. Miles has a rare form of dwarfism that causes a “floppy airway” that needs to be reopened with mechanical ventilation. He had briefly been put on a different ventilator in the past but couldn’t maintain safe levels of oxygen and suffered “blue spells” in which his skin changed color.

His Philips machine has been “his lifeline,” allowing him to live at home with his family. But Luczkowski said they had begun noticing black buildup when they changed a filter in the machine.

“It’s a very scary thing to hear that the machine that keeps your child alive could suddenly be the thing that’s harming them,” Luczkowski said.

[….]

Concerns have continued to mount. From April 2021 through April 2022, federal regulators have gotten more than 21,000 reports about medical issues potentially tied to the recalled devices — or malfunctions likely to cause injuries if they recurred — including 124 reports linking them to deaths. Cancer has been a stated concern: Since 2020, more than 1,100 such reports about Philips CPAP or BiPAP machines have included the words “cancer,” “tumor” or “tumour,” said Madris Kinard, chief executive of Device Events, which gathers data to track problems with medical devices.

Those medical device reports, which can be submitted by health professionals and patients as well as manufacturers, do not require verification that the device caused the injury or death; Philips stressed that submitting such reports “is not evidence that the device caused or contributed to the adverse outcome or event.”

However, Zuckerman said “it’s assumed that a lot of deaths and other serious injuries don’t get reported at all.”

In La Quinta, Matthew P. Stone counts himself as relatively lucky. The 61-year-old, who had been using a Philips CPAP machine for sleep apnea, had been able to fall back on an old device from another manufacturer.

But Stone, like others, has been galled by the way the recall has played out. At one point, Stone said, he tried to lodge a complaint with federal regulators and was referred to a Southern California number that kept cutting out before he could leave a message.

“I am so incredibly disappointed,” he said, “at the lack of advocacy by anybody involved.”

To read the entire article, click here.