Posts Tagged ‘drug safety’

FDA Commissioner Hamburg’s Report Card: NEJM provides a “perspective.”

Friday, October 15th, 2010

On October 6, 2010, The New England Journal of Medicine published a well written “perspective” on FDA Commissioner Dr. Margaret Hamburg’s efforts to “revive the FDA.” Her principal deputy commissioner, Dr. Joshua Sharfstein, echoed the same sentiment: “I keep a list of things I wish were moving faster and  a list of things moving at just the right speed, and these nothing on the second list.” (emphasis added). Dr. Hamburg is just completing her first year as commissioner at the FDA. We can only hope she remains and stays steadfast to the goals and objectives she has set out to achieve.

Since the NEJM is a subscription journal, I’m not sure if you will be able to access the full article, but I certainly hope you can.

Of significance for those of us who deal with FDA’s actions on virtually a daily basis, Commissioner Hamburg’s first quoted comment is of particular interest: ““You feel it differently at the FDA — how long it takes to move things through the system.” Welcome to bureaucracy at its finest, Commissioner.

What Commissioner Hamburg has done, however, deserves a lot of credit – at least in my non-politically based opinion.

Her objectives are listed by the NEJM article as being making “the FDA more nimble and proactive, restoring its credibility and refocusing staff on its public health mission, persuading Congress to boost funding for its expanding portfolio of responsibilities [and] sharpening its ability to deal with new science and globalization.” A very healthy list in all senses of the word.

Here is a list of just some of the actions taken and projects underway:

  • major recalls of over-the-counter pediatric medications
  • major recalls of salmonella-contaminated eggs
  • engaging in major debates over direct-to-consumer genetic testing
  • addressing safety concerns over the “blockbuster” diabetes drug, rosiglitzone
  • implementation of a 2009 law making the FDA responsible for tobacco regulation
  • making food-package labeling more evidence based
  • launching initiatives to “clarify and standardize” processes for evaluation drugs and medical devices
  • making more information public

As far as dealing with the issue of bureaucratic lethargy, Hamburg, Sharfstein and other key people at the FDA have created a new process known as “risk control review.” Under this program, field inspectors, who had previously been required to simply file reports that would eventually wend their way through the bureaucratic maze, when they detect “urgent health threats,” can now initiate direct meetings with key agency personnel to discuss taking emergency action. As a result of another initiative, an agency food-safety registry, in the first seven months of Hamburg’s leadership, more than 100 food-safety reports were submitted.

For those familiar with how the FDA worked, it is common knowledge that regulators of drugs and medical devices have been under pressure to approve them quickly. In response to criticisms of this so-called approval process, Dr. Hamburg and her staff have created an internal task force to review the way such decisions are being made at the Center for Drug Evaluation and Research (CDER). This approval process, called the 510(k) clearance process, was first met with outright dissent. After a “scathing internal FDA review” identified some of the major problems with the former way of doing business, officials at CDER adopted some of the recommended reforms – hopefully leading to “a clearer, fairer decision-making process.” Another IOM panel report is due next year; it is anticipated that further reforms in such process will be recommended.

Dr. Hamburg’s mantra has been – “follow the science.” Her response to the questions from her people at FDA in terms of what they can do about concerns of immediate public health safety is reported as being – “What do you think the right thing to do is from a public health perspective?” Seems like the Commissioner is a good listener and a pro-active responder.

Needless to say, Dr. Hamburg’s activities could well fill pages of text. She faces issues relating to globalization (ensuring products made overseas and entering our marketplace are safe), funding for her agency (a never-ending task seeking dollars for her projects and people in a seemingly pitiful federal budget), improvement of post-marketing safety studies, implementing and overseeing a data-mining system used to analyze electronic safety records (Harvard Pilgrim Health Care’s Sentinel System) to improve numerous aspects of patient safety, and forging key partnerships with private industry and academia scientists to “get it right” – to name just some of the projects for which her agency is responsible.

All one can say – thank goodness the Doctor is in the house! We wish her continued strength, patience, perseverance and success.

Bone-Strengthening Drugs and Esophageal Cancer – Potential Link Should Not Be Ignored

Monday, September 6th, 2010

In the last year, there has been considerable debate about the link between bone-strengthening drugs, also known as bisphosphonates, and esophageal cancer. It started last year when the FDA released information regarding nearly two dozen cases of esophageal cancer in patients that have been taking oral bisphosphonates such as Fosamax. According to Diane Wysowski, PhD, the FDA official who first claimed that there may be a link between bisphosphonates and esophageal cancer, the FDA has continued to receive reports of esophageal cancer in patients on bisphosphonates since 2009.

The FDA’s announcement was followed by the release of a research study of more than 80,000 people, which focused on the link between bisphosphonates and esophageal cancer. The study, which was recently published in the Journal of the American Medical Association, claims that the link between bisphosphonates and an increased risk for developing esophageal cancer is insignificant.

“[Researchers] compared the rates of esophageal and stomach cancer in 83,652 people, half of whom had received at least one prescription for oral bisphosphonates in the previous decade. Just over 80% of the participants were women, and the average age was 70. … Eighty-nine and 92 cases of esophageal cancer were reported in the bisphosphonate and control groups, respectively, as were 49 and 57 cases of stomach cancer—a negligible difference.”

The authors conceded, however, that the study was not perfect.  For example, the study lasted for only 4.5 years, an insufficient period of time to measure the risk of esophageal cancer among patients on bisphosphonates.  Researchers were also not able to insure that all of the study participants actually took bisphosphonates as prescribed. Additionally, they did not account for other comorbidities and risk factors that might increase the risk for esophageal cancer.

According to Chris Cardwell, PhD, the study’s lead author: “Our study is the largest to date, but on the basis of our results we cannot rule out small increases in esophageal cancer risk in individuals taking bisphosphonates.”

A more recent study on the same subject was published last week in the British Journal of Medicine.  This study concluded that that there is an increase in the incidence of esophageal cancer among patients who have been taking oral bisphosphonates for several years (ten or more prescriptions or prescriptions over the course of five years).

“Researchers tracked almost 3,000 people with cancer of the esophagus or throat for eight years and compared them with a group of 15,000 people who did not have the disease. All were over age 40. The scientists found that 90 of the cancer patients had been prescribed the bone-building drugs, while 345 people in the larger group were taking the medication.”

According to this latest research study, the normal incidence of esophageal cancer among patients 60-79 who are not on oral bisphosphonates is about one per 1000. In the same age group, researchers found that the incidence of esophageal cancer doubled among those patients that have been on oral bisphosphonates for several years. It is suspected that bisphosphonates cause inflammation of the esophagus that may predisposes the patient to esophageal cancer.

Both of these studies seem to indicate a positive correlation between oral bisphosphonates and esophageal cancer.  Whether or not the correlation is significant is a determination the patient should be making with his or her physician.  The risk for developing esophageal cancer should not be ignored considering the number of people who take oral bisphosphonates on a regular basis. It is estimated that about 10 million women are diagnosed with osteoporosis in the U.S.  In this population, about 4.7 million take oral bisphosphonates on a regular basis.

If you have been taking oral bisphosphonates for five years or longer, discuss the risk of developing esophageal cancer with your physician and explore available alternatives if you are at risk. More important perhaps, be on the lookout for signs and symptoms consistent with esophageal cancer. They include throat, chest and digestive discomfort as well as difficulty swallowing.  If you have these symptoms, consult a physician immediately.

Contributing author: Jon Stefanuca