Princess Health and Some FDA History, with "Safety ... at the Back of the Bus.". Princessiccia

Princess Health and Some FDA History, with "Safety ... at the Back of the Bus.". Princessiccia

FDA

Gusty 12:13 Add Comment

The Boston Globe provided some historical context for how the US Food and Drug Administration (FDA) got into its current troubles. Here are some salient points:

• In the late 1980's, the FDA was under pressure from gay activists to speed up its approval process for drugs for HIV infections. "Protesters stood atop buses and stopped traffic. Some broke into the FDA and smashed computers. They hung then-FDA commissioner Frank Young in effigy." Protesters chanted "Hey, hey, FDA, how many people have you killed today."
• Pharmaceutical companies also wanted to speed up the approval process, and threatened to "move research, development, and clinical studies abroad" if their wishes were denied.
• In 1992, in response to budget pressure, Congress passed the Prescription Drug User Fee Act, which would speed up the FDA review process in exchange for direct fees paid by the pharmaceutical companies.
• Since then, total user fees paid to the FDA have climbed from US $87.5 million in 1997 to $382 million this year. The speed of reviews has also increased.
• However, the need for speed, plus financing coming direct from pharmaceutical companies appeared to change the FDA culture. The article included several charges that FDA personnel were pressured and intimidated to speed drugs along even if they had doubts about their safety. For example, Dr. Jerry Avorn of Harvard alleged "the purposeful supppression of individuals within FDA who are concerned about problems and are told 'Don't make waves. We need to get this drug approved.'" Dr. Erick Turner said that reviewers who tried to delay approvals due to safety concerns were called before "tribunals." The reviewer who tried to delay the approval of Rezulin because he suspected it would cause liver problems was taken off the case after he got in a verbal altercation with an official of Rezulin's manufacturer, Warner-Lambert. Rezulin was taken off the market in 1997.
• The article ended with a quote from FDA whistle-blower David Graham, "Safety, as I a said before, is at the back of the bus."

A few more global comments.
One can sympathize with the "activists" who applied political pressure via 1960's style street theatre to try to speed up treatment for a then rapidly fatal disease. However, their pressure had broader effects than they intended, and hence unintended consequences.
It seemed reasonable to essentially tax pharmaceutical companies for a rapid review process that would benefit them (as well as the public, it was hoped.) However, sending the tax money direct to the FDA in the form of "user fees" created an institutional conflict of interest.
It is upsetting that so many of the stories we discuss on this blog culminate in the final common pathway of intimidation of well-meaning professionals, physicians, and scientists by overbearing bureaucrats and administrators. All too often the coincidence of self-interest and power leads to censorship and intimidation.

Princess Health and Some FDA History, with "Safety ... at the Back of the Bus.".Princessiccia

Princess Health and Some FDA History, with "Safety ... at the Back of the Bus.".Princessiccia

FDA

Gusty 12:13 Add Comment

The Boston Globe provided some historical context for how the US Food and Drug Administration (FDA) got into its current troubles. Here are some salient points:

• In the late 1980's, the FDA was under pressure from gay activists to speed up its approval process for drugs for HIV infections. "Protesters stood atop buses and stopped traffic. Some broke into the FDA and smashed computers. They hung then-FDA commissioner Frank Young in effigy." Protesters chanted "Hey, hey, FDA, how many people have you killed today."
• Pharmaceutical companies also wanted to speed up the approval process, and threatened to "move research, development, and clinical studies abroad" if their wishes were denied.
• In 1992, in response to budget pressure, Congress passed the Prescription Drug User Fee Act, which would speed up the FDA review process in exchange for direct fees paid by the pharmaceutical companies.
• Since then, total user fees paid to the FDA have climbed from US $87.5 million in 1997 to $382 million this year. The speed of reviews has also increased.
• However, the need for speed, plus financing coming direct from pharmaceutical companies appeared to change the FDA culture. The article included several charges that FDA personnel were pressured and intimidated to speed drugs along even if they had doubts about their safety. For example, Dr. Jerry Avorn of Harvard alleged "the purposeful supppression of individuals within FDA who are concerned about problems and are told 'Don't make waves. We need to get this drug approved.'" Dr. Erick Turner said that reviewers who tried to delay approvals due to safety concerns were called before "tribunals." The reviewer who tried to delay the approval of Rezulin because he suspected it would cause liver problems was taken off the case after he got in a verbal altercation with an official of Rezulin's manufacturer, Warner-Lambert. Rezulin was taken off the market in 1997.
• The article ended with a quote from FDA whistle-blower David Graham, "Safety, as I a said before, is at the back of the bus."

A few more global comments.
One can sympathize with the "activists" who applied political pressure via 1960's style street theatre to try to speed up treatment for a then rapidly fatal disease. However, their pressure had broader effects than they intended, and hence unintended consequences.
It seemed reasonable to essentially tax pharmaceutical companies for a rapid review process that would benefit them (as well as the public, it was hoped.) However, sending the tax money direct to the FDA in the form of "user fees" created an institutional conflict of interest.
It is upsetting that so many of the stories we discuss on this blog culminate in the final common pathway of intimidation of well-meaning professionals, physicians, and scientists by overbearing bureaucrats and administrators. All too often the coincidence of self-interest and power leads to censorship and intimidation.

Princess Health and The End of an Era: Maurice Hilleman, Ph.D.. Princessiccia

Princess Health and The End of an Era: Maurice Hilleman, Ph.D.. Princessiccia

Gusty 11:13 Add Comment

The obituary of a pioneer in vaccine development, Maurice Hilleman, Ph.D., appeared today. Dr. Hilleman worked since 1957 at Merck & Co., Inc., and saved millions of lives by developing vaccines against mumps, measles, chicken pox, rubella, and other infectious diseases.

The praise in the obituary, reproduced below, was highly merited:

"It's safe to say his vaccines save in the order of eight million lives a year," said Paul A. Offit, chief of infectious diseases at Children's Hospital of Philadelphia. "I think it can be said without hyperbole that he was a scientist who saved more lives than any other modern scientist."

Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases, called Hilleman's collective life work "unparalleled."

Dr. Hilleman, who lived in Springfield Township, Montgomery County, near the Chestnut Hill section of Philadelphia, spent most of his career working for what is now Merck & Co., where his focus was always on the practical application of science, not simply research for the sake of research. "Science has to produce something useful," Dr. Hilleman said in a 1999 Inquirer article that profiled his life. "That's the payback to society for support of the enterprise."

... Hilleman also pioneered the development of vaccines against hepatitis A, hepatitis B and bacterial meningitis, among other diseases.

Early in his career, while working at Walter Reed Army Institute of Research in Washington, Hilleman figured out how the flu virus undergoes genetic changes that can cause deadly flu pandemics. That knowledge is used every year by scientists concocting the annual flu vaccine.

When Hilleman's daughter, Jeryl Lynn, then 5, came down with mumps in 1963, he took a culture from her throat and took it to his lab, where he grew and isolated the mumps virus. That led in 1967 to the first vaccine against mumps, a disease that used to infect 200,000 children a year in the United States.

I came to know Dr. Hilleman quite well during my tenure at Merck, managing Merck Research Labs' internal scientific libraries at West Point, PA and Rahway, NJ, the major R&D sites. He was an avid customer of services (at the West Point library in particular) in his activity of writing superb review papers of the scientific literature on topics related to vaccines, preventive medicine, and even bioterrorism. We had numerous conversations in the privacy of my office when he came by to visit.

He shared my views that good science cannot be forced but must be nurtured, and that in particular, science libraries and access to scientific literature in both electronic and printed form were essential for the best science to occur. He was kind enough to write this letter to help in my championing of funding for the science library departments I managed.

The obituaries note that Hilleman was known for punctuating his talk with frequent "damn-its." "He was a wonderfully spirited, cantankerous character," as noted in the obituaries. This is quite true; however, in my conversations with him, such epithets were often directed at the opinions of those without scientific or medical credentials who were now making management decisions in many sectors of healthcare. His belief was that healthcare innovations would come from scientists and clinicians establishing mental connections and "pulling pertinent information together" throughout the biomedical literature to guide their research along creative and productive paths - and avoid costly paths already known somewhere to have not worked - not through "management mysticism" and the "syndrome of inappropriate confidence in computers." These expressions of mine amused Dr. Hilleman, who refused to use IT.

It is with regret that I was separated from my position in late 2003 along with approximately 4,400 others as a result of pipeline failures and failure to achieve double-digit profit growth, and could not continue my informatics advocacy. It is also with regret that I became aware of the recent closure of one of the library facilities I managed, as a result of now-former employees contacting me for references as they seek new employment in a tight market. As Dr. Hilleman might say, "damn it."

Dr. Hilleman died at age 85 and represents an older era of scientists who made their contributions the hard way - via dedicated use of grey matter and thorough exploration and knowledge of the scientific literature. He is reminiscent of an early mentor of my career, the late heart surgeon Victor P. Satinsky, M.D. of Hahnemann Medical College, who ran NSF science programs in the early 1970's for high school students interested in biomedicine. Dr. Satinsky was also a no-nonsense and highly inventive clinician who demanded critical thinking ("critical thinking always" was his motto) and the need for true expertise in biomedical science by those in leadership roles. My interests in medicine and computing, as well as many of my no-nonsense attitudes regarding clinical medicine, were formulated under his aegis. Perhaps that is why Dr. Hilleman and I seemed to see eye-to-eye on numerous matters.

Dr. Hilleman's death truly marks the end of an era. May he rest in peace.

Addendum: the article at Slate "The Unsung Vaccinologist" by Arthur Allen, who is writing a history of vaccination, captures Dr. Hilleman's essense well.

-- SS

Princess Health and The End of an Era: Maurice Hilleman, Ph.D..Princessiccia

Princess Health and The End of an Era: Maurice Hilleman, Ph.D..Princessiccia

Gusty 11:13 Add Comment

The obituary of a pioneer in vaccine development, Maurice Hilleman, Ph.D., appeared today. Dr. Hilleman worked since 1957 at Merck & Co., Inc., and saved millions of lives by developing vaccines against mumps, measles, chicken pox, rubella, and other infectious diseases.

The praise in the obituary, reproduced below, was highly merited:

"It's safe to say his vaccines save in the order of eight million lives a year," said Paul A. Offit, chief of infectious diseases at Children's Hospital of Philadelphia. "I think it can be said without hyperbole that he was a scientist who saved more lives than any other modern scientist."

Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases, called Hilleman's collective life work "unparalleled."

Dr. Hilleman, who lived in Springfield Township, Montgomery County, near the Chestnut Hill section of Philadelphia, spent most of his career working for what is now Merck & Co., where his focus was always on the practical application of science, not simply research for the sake of research. "Science has to produce something useful," Dr. Hilleman said in a 1999 Inquirer article that profiled his life. "That's the payback to society for support of the enterprise."

... Hilleman also pioneered the development of vaccines against hepatitis A, hepatitis B and bacterial meningitis, among other diseases.

Early in his career, while working at Walter Reed Army Institute of Research in Washington, Hilleman figured out how the flu virus undergoes genetic changes that can cause deadly flu pandemics. That knowledge is used every year by scientists concocting the annual flu vaccine.

When Hilleman's daughter, Jeryl Lynn, then 5, came down with mumps in 1963, he took a culture from her throat and took it to his lab, where he grew and isolated the mumps virus. That led in 1967 to the first vaccine against mumps, a disease that used to infect 200,000 children a year in the United States.

I came to know Dr. Hilleman quite well during my tenure at Merck, managing Merck Research Labs' internal scientific libraries at West Point, PA and Rahway, NJ, the major R&D sites. He was an avid customer of services (at the West Point library in particular) in his activity of writing superb review papers of the scientific literature on topics related to vaccines, preventive medicine, and even bioterrorism. We had numerous conversations in the privacy of my office when he came by to visit.

He shared my views that good science cannot be forced but must be nurtured, and that in particular, science libraries and access to scientific literature in both electronic and printed form were essential for the best science to occur. He was kind enough to write this letter to help in my championing of funding for the science library departments I managed.

The obituaries note that Hilleman was known for punctuating his talk with frequent "damn-its." "He was a wonderfully spirited, cantankerous character," as noted in the obituaries. This is quite true; however, in my conversations with him, such epithets were often directed at the opinions of those without scientific or medical credentials who were now making management decisions in many sectors of healthcare. His belief was that healthcare innovations would come from scientists and clinicians establishing mental connections and "pulling pertinent information together" throughout the biomedical literature to guide their research along creative and productive paths - and avoid costly paths already known somewhere to have not worked - not through "management mysticism" and the "syndrome of inappropriate confidence in computers." These expressions of mine amused Dr. Hilleman, who refused to use IT.

It is with regret that I was separated from my position in late 2003 along with approximately 4,400 others as a result of pipeline failures and failure to achieve double-digit profit growth, and could not continue my informatics advocacy. It is also with regret that I became aware of the recent closure of one of the library facilities I managed, as a result of now-former employees contacting me for references as they seek new employment in a tight market. As Dr. Hilleman might say, "damn it."

Dr. Hilleman died at age 85 and represents an older era of scientists who made their contributions the hard way - via dedicated use of grey matter and thorough exploration and knowledge of the scientific literature. He is reminiscent of an early mentor of my career, the late heart surgeon Victor P. Satinsky, M.D. of Hahnemann Medical College, who ran NSF science programs in the early 1970's for high school students interested in biomedicine. Dr. Satinsky was also a no-nonsense and highly inventive clinician who demanded critical thinking ("critical thinking always" was his motto) and the need for true expertise in biomedical science by those in leadership roles. My interests in medicine and computing, as well as many of my no-nonsense attitudes regarding clinical medicine, were formulated under his aegis. Perhaps that is why Dr. Hilleman and I seemed to see eye-to-eye on numerous matters.

Dr. Hilleman's death truly marks the end of an era. May he rest in peace.

Addendum: the article at Slate "The Unsung Vaccinologist" by Arthur Allen, who is writing a history of vaccination, captures Dr. Hilleman's essense well.

-- SS

Princess Health and "Climate of Alarm Described at NIH". Princessiccia

Princess Health and "Climate of Alarm Described at NIH". Princessiccia

NIH whistle-blowers

Gusty 11:41 Add Comment

And here is yet another story about problems at the NIH, this time allegations about intimidation of whistle-blowers. The Associated Press obtained testimony charging that NIH officials squelched safety concerns tin the rush to try "to cure AIDS." For example,

• "It can be fairly uncomfortable. There are a number of things that you just don't talk about. You don't hold up any projects even if you feel there are safety issues for certain projects." (Testimony by Betsy Smith, NIAID)
• "I think we [safety officials] got in the way and that we were an impediment to the science." Division managers were "totally unsupportive" of safety and were responding to "tremendous pressure" from drug companies. "I think the culture was certainly strong for a period of time that the ends could justify the means." (Testimony by Mary Anne Luzar, Ph.D., Chief Regulatory Affairs Section, Pharmaceutical and Regulatory Affairs Branch, DAIDS)

Yet more clean up work is ahead for Director Zernouni. But this provides yet more justification for his argument that widespread changes are needed.

Princess Health and "Climate of Alarm Described at NIH".Princessiccia

Princess Health and "Climate of Alarm Described at NIH".Princessiccia

NIH whistle-blowers

Gusty 11:41 Add Comment

And here is yet another story about problems at the NIH, this time allegations about intimidation of whistle-blowers. The Associated Press obtained testimony charging that NIH officials squelched safety concerns tin the rush to try "to cure AIDS." For example,

• "It can be fairly uncomfortable. There are a number of things that you just don't talk about. You don't hold up any projects even if you feel there are safety issues for certain projects." (Testimony by Betsy Smith, NIAID)
• "I think we [safety officials] got in the way and that we were an impediment to the science." Division managers were "totally unsupportive" of safety and were responding to "tremendous pressure" from drug companies. "I think the culture was certainly strong for a period of time that the ends could justify the means." (Testimony by Mary Anne Luzar, Ph.D., Chief Regulatory Affairs Section, Pharmaceutical and Regulatory Affairs Branch, DAIDS)

Yet more clean up work is ahead for Director Zernouni. But this provides yet more justification for his argument that widespread changes are needed.

Princess Health and "The Price of NIH Credibility". Princessiccia

Princess Health and "The Price of NIH Credibility". Princessiccia

conflicts of interest NIH

Gusty 11:18 Add Comment

An excellent editorial in the Los Angeles Times. Let me just provide some quotes.

• "Protesting NIH staff scientists and members of Congress opposing the new regulations would have us think [NIH Director] Zerhouni intends to bulldoze the agency's 300-acre campus in Bethesda, MD, and turn it into a garment district sweatshop."
• "Zerhouni's critics claim that the new rules will lead to a cataclysmic brain drain. Yes, a few people might leave. But the rules also should bolster the agency's status as one of the few places where scientists can work with true autonomy, free from the increasingly brazen control that biomedical industries are exerting over research."
• "A Government Accountability [sic] Office study released two months ago found that the previous NIH policies 'could call into question the quality and independence of federally funded research.' There could hardly be a better reason for change."
• "At Senate hearings last week, Sen. Tom Harking (D-Iowa) sided with the complaining scientists and dangled a possible NIH budget increase in an implicit tit-for-tat for softer rules. That's just strong-arming."
• "Zerhouni is trying to restore scientific credibility to an agency that had allowed one of its top scientists, P. Trey Sutherland III, to pocket half a million dollars from Pfizer Inc. even as he was evaluating Pfizer drugs for NIH. Would [Senator] Harkin want to buy a drug for his family that was developed in this manner?"

Couldn't say it better myself.