Definition of a Guinea Pig: Ask the FDA!

Barely Half of Postmarket Studies Completed After 5 Years

FDA fails to enforce requirements

• by Larry Husten, CardioBrief September 20, 2017 
• 
  

Pharmaceutical and device companies are often taking advantage of a lenient (or, some would say, negligent) FDA to shirk their obligation to perform timely post-approval studies, a new Perspective published in the New England Journal of Medicine shows.

The topic has gained increasing  visibility and importance as the FDA has granted approval to many new drugs and devices without all the evidence that might ideally be required.For safety as well as efficacy, the FDA has allowed much of the burden of proof to shift from pre-approval to the post-approval period.

But in an analysis of 614 post-approval requirements and commitments imposed by the FDA in 2009 and 2010 (the first full years after the FDA gained the power to require these studies), Steven Woloshin at Dartmouth Institute for Health Policy and Clinical Practice and colleagues showed that only 54% of these studies were completed after 5-6 years. They found that 20% of "required" studies had not been started and 25% were delayed or ongoing as of September 2015.

"It's not a secret that we need a better post-market system," said former FDA Commissioner Robert Califf, now at Duke University. "The good news is that technology is no longer the limiting factor -- it's all about culture, organization and priority setting by policy makers, clinicians and patients and their 'carers' (families and loved ones)."

The authors observed that in many cases there didn't appear to be any good reason for the delays. For instance, more than 5 years after approval of buprenorphine/naloxone film (Suboxone), no protocol had been submitted for assessing the risk of QT-interval prolongation, "even though the design of such studies is highly standardized and participants are observed for a limited period."

"The slow, irregular pace of post-approval studies contrasts starkly with the short, rigid deadlines and other shortcuts used to speed marketing approval," the authors wrote.

The FDA should "do more to ensure that sponsors meet post-approval deadlines," the authors urged. Although the FDA has the power to impose fines or other penalties on companies that fail to live up to their obligations, "to our knowledge, it has never imposed such fines." They also recommend that the FDA set shorter deadlines for post-approval studies.

"Woloshin and colleagues offer some useful insights into the FDA's use of post-approval studies to confirm and further evaluate drugs' safety and efficacy at the time of approval," said Joe Ross of Yale University. "While more than half were completed, many were not. This study is only made possible by the efforts at FDA to provide public transparency of the post-approval requirements, but more information could help the public and the profession understand why certain requirements were not fulfilled, whether these studies were intended to provide key clinical information to inform practice (as opposed to safety info that instead came from another clinical study), and even for those studies that were completed, whether the results were published and made available."

Sanjay Kaul of Cedars-Sinai Medical Center said that it is not unreasonable to shift "the regulatory burden from the pre-approval phase to a life cycle-based approach. However, the success of such an approach is predicated on a rigorous and timely post-approval phase. That 1 in 5 post approval studies had not even been started after 5 to 6 years calls into question the degree to which the changes in the FDA's regulatory authority in 2007 have resolved the challenge of reducing the number of unfulfilled post-approval requirements. This can hardly be reassuring given the 21st Century Cures Act which calls for faster marketing of drugs and devices at the cost of stringent evidentiary standards! Even though the FDA has congress-legislated authority to revoke approval of drugs and devices that failed to confirm clinical benefit on post approval studies, it rarely does so! It is difficult to put the genie back into the bottle."

The "bottom line," said Kaul, is that "marketing drugs and devices faster can only be justified if there are much better post-market data to reliably support efficacy and safety."

• https://www.medpagetoday.com/cardiology/cardiobrief/68035

Cardiologists Arrested: Human Experimentation

http://www.forbes.com/sites/larryhusten/2012/11/11/nine-italian-cardiologists-arrested-in-broad-investigation-of-research-fraud-and-misconduct/

Larry Husten, Contributor

A medical journalist covering cardiology news.

PHARMA & HEALTHCARE | 11/11/2012 @ 7:59PM  (FiDA highlight)

NineItalian CardiologistsArrested In BroadInvestigation Of Research Fraud And Misconduct

Nine Italian cardiologists have been arrested as part of a broad investigation into serious medical misconduct at Modena Hospital, according to multiple reports in the Italian media. The investigation encompasses at least 67 other individuals and a dozen medical equipment companies, including 6 foreign companies. The charges include conspiracy, fraud, embezzlement, bribery, forgery and performing unauthorized clinicaltrials. Several news reports mentioned that stents and angioplasty balloons were involved.
According to one Italian website, the investigation started in 2011 in response to allegations by a group, Amici del Cuore (Friends of the Heart), that patients at the Modena Hospital (Policlinico di Modena) received treatments and procedures as part of unauthorized experiments. In some cases the procedures may have resulted in fatal outcomes. The accused physicians ”performed experimental tests without making it known to patients for the sole purpose of writing about these trials in specialized magazines collecting money through bogus non-profit organization,” the website reported. [All translations in this story taken from Google Translate.]

“We wanted to ask questions about certain procedures that went far beyond the standard ones, and that seemed unusual to us,” the president of Friends of the Heart, Professor Giovanni Spinella, told Il Salvagente. “We were aware that invasive procedures were performed, often on peripheral organs, and sometimes had little to do [with] the heart. And unfortunately had caused discomfort and damage to several patients.”

Another Italian site quoted a police official who called it “a major operation” and said the accused “committed human clinical trials without authorization and installed medical devices and equipment defective in patients unaware of being subjected to an experimental treatment.” The accused physicians then “created false medical records to cover medical errors.” The Italian media said the investigation included recordings of telephone conversations between the suspects. The Italian police named the operation camici sporchi (“dirty gowns”).

The most prominent person arrested was Maria Grazia Modena, the chief of cardiology at Modena Hospital and a former president of the Italian Society of Cardiology. (Grazia Modena was the subject of a profile in Circulation European Perspectives (PDF) in 2007.) Modena, 60 years old, was trained partly at New York University and the Mayo Clinic. The second main focus of the investigation appears to be the head of the catheterization laboratory at the hospital, Giuseppe Sangiorgi. According to news reports, he is the only arrested physician who is still in jail.

Here are the names of the nine physicians:

•               Maria Grazia Modena, chief of cardiology

•               Giuseppe Sangiorgi, head of the catheterization laboratory

•               Luigi Vincenzo Politi

•               April Alexander

•               Simona Lambertini

•               Giuseppe Biondi Zoccai

•               Fabrizio Clement

•               Alessandro Mauriello

Andrea Amato, 36

High Standards for FDA leaders?

•                Police & Fire

FDA Official Pleads Guilty to Prostitution Charge, GetsOne Day of Probation

William Maisel is one of three men who pleaded guilty to charges of soliciting prostitution during a sting carried out by the Howard County Police Department.

•                By Brian Hooks

•                September 25, 2012

Dr. William Maisel, the cardiologist and Food and Drug Administration (FDA) official charged by the Howard County Police Department in July with soliciting a prostitute, recently pleaded guilty in district court.

Maisel is the deputy director of the Center for Devices and Radiological Health (CDRH), which has become embroiled in an employee-spying scandal. He received one day of probation and paid $257.50 in fees and courts costs, according to T. Wayne Kirwan, spokesperson for the Howard County State's Attorney's Office.

Maisel's one day of probation ended on Friday, Sept. 21, according to Kirwan.  

According to charging documents from district court, an undercover female police officer approached Maisel at a restaurant on Route 1 in Jessup and asked him if he wanted "a date." Maisel agreed and asked how much it would cost for sex.

Three of the other men arrested in the prostitution sting also pleaded guilty and received probation, according to Kirwan, but only one faces probation longer than two days. Five additional men charged are still facing court dates.  

In a matter unrelated to Maisel's arrest, the National Whistleblower Center (NWC) is asking whether the charges against him are indicative of his involvement in the FDA surveillance activity, reports The Washington Post.  

According to the NWC, Maisel was responsible for firing Ewa Czerska–one of the FDA employees observed in the surveillance–and the whistleblowers are asking whether Maisel's work will be investigated, reports The Post.  

FDA spokesperson Erica Jefferson told The Post that the administration considers the solicitation charges "a personal matter" that would not affect his work.

Cardiologist William MaiselArrested In Prostitution Sting Operation

Larry Husten, Contributor to Forbes

PHARMA & HEALTHCARE | 8/01/2012 @ 3:34PM

Cardiologist William Maisel, the deputy director for science at the FDA Center of Devices and Radiological Health, was arrested on prostitution charges after being caught in an undercover sting operation in North Laurel, Maryland. Maisel was one of 10 men arrested on July 13.

The Savage-Guilford Patch reported that Maisel ”approached a plain-clothed female police officer and offered money for sex.” He is scheduled to appear in Howard County District Court on Sept. 20.

According to Pharmalot, the news ”was greeted with a mixture of shock and sadness inside the FDA, which is treating the incident as a personal matter, according to an FDA spokeswoman. The arrest, she tells us, ‘has nothing to do with the work he is doing here.’” Maisel did not respond to a request for comment from Pharmalot.

Prior to joining the FDA Maisel had been the director of the Medical Device Safety Institute at Beth Israel Deaconess Medical Center and an assistant professor of medicine at Harvard Medical School. Maisel was a vocal advocate for better safety measures and FDA reform in the wake of the recall of the Sprint Fidelis ICD lead recall.