Innovative therapy

Years ago, at a departmental meeting, the neurologists informed the general pediatricians that they were going to try out a new therapy for autism. Autism recently had been linked to inflammation of the gastrointestinal system. One of the articles that asserted that link is the now retracted Lancet article by Andrew Wakefield et al., which also falsely linked MMR and autism (Lancet 1998;35:637-41).

At the time, the misrepresentations in that article had not yet been fully revealed.

The treatment the neurologists were considering would utilize the hormone secretin. [Please note that the most recent Cochrane Review in 2012 reaffirmed the 2005 review repudiating this therapy (Cochrane Database Syst. Rev..2012 ;4 [doi: 10.1002/14651858.CD003495.pub3]). However, Mr. Wakefield is still advocating some form of therapy.] Secretin was first isolated in 1902 and has the distinction of being the first hormone isolated by Western science. A synthetic polypeptide analogue has been created. The local neurologists had read about this new therapy for autism and wanted to see if and how it worked. It is not unusual for new therapies to be adopted by subspecialists and then make their way into the armamentarium of general pediatricians. Most drugs I prescribe are not Food and Drug Administration approved in children, but have been adopted for use by other pediatricians and subspecialists.

The aforementioned multispecialty group did not participate in much clinical research. There was an active local institutional review board (IRB). However, in one of the strange paradoxes of medical law, as long as the neurologists were going to haphazardly try the secretin in a few cases, without any scientific control group and without any intention of publishing their results, they were free to do so if, in their professional opinion, they felt the innovative use of the medication might help. I warned them that if they made any attempt to compare results with other patients in an organized, scientific fashion, then IRB approval would be required. I expected that would be very difficult, if not impossible, to obtain.

There is a long and sad history of inadequate protection of research subjects in U.S. medicine. Some protections were put in place in the 1970s. Principles for those protections were outlined in the Belmont Report in 1978. From that report: "When a clinician departs in a significant way from standard or accepted practice, the innovation does not, in and of itself, constitute research. The fact that a procedure is ‘experimental,’ in the sense of new, untested or different, does not automatically place it in the category of research."

And so, we really have a three-tier system. Those who claim to be doing research should be following strict ethical guidelines, using carefully reviewed methodologies, publishing in peer-reviewed journals, and be overseen by the local IRB. The second tier consists of physicians who are taking FDA-approved medications and using them in off-label ways. A medical license grants a physician that right. It is, however, illegal for a pharmaceutical company to detail physicians on these off-label uses. The FDA has cracked down on that recently, including fining Pfizer $2.3 billion 4 years ago. Finally, in the bottom tier, we have late-night infomercials promising for 30 minutes how all these complementary therapies, nutraceuticals, and dietary supplements will make ailments go away while flashing for a few seconds on the screen the disclaimer: "These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease."

People who watch late-night TV are fully availing themselves of their liberty, guaranteed by congressional action, to listen to ridiculous claims unfiltered by the science and conventional wisdom of the medical establishment. At the other extreme, the IRB protects research subjects, sometimes to excess. A group of hospitalists at 12 hospitals each sent surveys to 20 local physicians asking which details they would like to find in a discharge summary. That activity required each local investigator to take 3 hours of training on research protections. It also required approval by the local IRBs at each hospital.

In between these extremes, in everyday clinical practice, the primary form of protection is informed consent. Physicians have an obligation to provide the information that a reasonable patient would want to know in order to make a rational decision about embarking on a course of treatment. Failure to provide this is a breach of the standard of care, which means, if the patient suffers harm, they may have a good case for claiming malpractice.

There have been two recent news articles on this subject that caught my eye.

In the Oregon case, a physician denied wrongdoing but agreed in the future to inform his patients that he gets what could be construed as a kickback from the medical supply company for implanting a particular brand of pacemaker.

In the Sacramento case, two neurosurgeons resigned from the University of California, Davis, after a controversy over the inadequacy of research subject protections in their trial of a novel approach for treating a highly malignant brain cancer with "probiotic intracranial therapy," or the introduction of live bowel bacteria, Enterobacter aerogenes, directly into their patients’ brains or bone flaps. The doctors theorized that an infection might stimulate the patients’ immune systems and prolong their lives.

Physicians who use medications for off-label uses are well advised to be sure they are obtaining and documenting informed consent from their patients. Informed consent requires the physician to have provided all relevant details that a reasonable patient would want to know before making a decision. IRBs are in place to protect research subjects. There is a problem, however, with having a higher tier of protection and the associated burdensome paperwork. Powell’s 4th rule of medical ethics: If you raise the bar high enough, people walk under it.

Dr. Powell practices as a hospitalist at SSM Cardinal Glennon Children’s Medical Center in St. Louis. He is associate professor of pediatrics at Saint Louis University. He is also listserv moderator for the AAP Section on Hospital Medicine and is a member of the Law and Bioethics Affinity Group of the American Society for Bioethics and Humanities. He said that he had no financial conflicts of interest. Readers can e-mail Dr. Powell at [email protected].

Years ago, at a departmental meeting, the neurologists informed the general pediatricians that they were going to try out a new therapy for autism. Autism recently had been linked to inflammation of the gastrointestinal system. One of the articles that asserted that link is the now retracted Lancet article by Andrew Wakefield et al., which also falsely linked MMR and autism (Lancet 1998;35:637-41).

At the time, the misrepresentations in that article had not yet been fully revealed.

The treatment the neurologists were considering would utilize the hormone secretin. [Please note that the most recent Cochrane Review in 2012 reaffirmed the 2005 review repudiating this therapy (Cochrane Database Syst. Rev..2012 ;4 [doi: 10.1002/14651858.CD003495.pub3]). However, Mr. Wakefield is still advocating some form of therapy.] Secretin was first isolated in 1902 and has the distinction of being the first hormone isolated by Western science. A synthetic polypeptide analogue has been created. The local neurologists had read about this new therapy for autism and wanted to see if and how it worked. It is not unusual for new therapies to be adopted by subspecialists and then make their way into the armamentarium of general pediatricians. Most drugs I prescribe are not Food and Drug Administration approved in children, but have been adopted for use by other pediatricians and subspecialists.

The aforementioned multispecialty group did not participate in much clinical research. There was an active local institutional review board (IRB). However, in one of the strange paradoxes of medical law, as long as the neurologists were going to haphazardly try the secretin in a few cases, without any scientific control group and without any intention of publishing their results, they were free to do so if, in their professional opinion, they felt the innovative use of the medication might help. I warned them that if they made any attempt to compare results with other patients in an organized, scientific fashion, then IRB approval would be required. I expected that would be very difficult, if not impossible, to obtain.

There is a long and sad history of inadequate protection of research subjects in U.S. medicine. Some protections were put in place in the 1970s. Principles for those protections were outlined in the Belmont Report in 1978. From that report: "When a clinician departs in a significant way from standard or accepted practice, the innovation does not, in and of itself, constitute research. The fact that a procedure is ‘experimental,’ in the sense of new, untested or different, does not automatically place it in the category of research."

And so, we really have a three-tier system. Those who claim to be doing research should be following strict ethical guidelines, using carefully reviewed methodologies, publishing in peer-reviewed journals, and be overseen by the local IRB. The second tier consists of physicians who are taking FDA-approved medications and using them in off-label ways. A medical license grants a physician that right. It is, however, illegal for a pharmaceutical company to detail physicians on these off-label uses. The FDA has cracked down on that recently, including fining Pfizer $2.3 billion 4 years ago. Finally, in the bottom tier, we have late-night infomercials promising for 30 minutes how all these complementary therapies, nutraceuticals, and dietary supplements will make ailments go away while flashing for a few seconds on the screen the disclaimer: "These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease."

People who watch late-night TV are fully availing themselves of their liberty, guaranteed by congressional action, to listen to ridiculous claims unfiltered by the science and conventional wisdom of the medical establishment. At the other extreme, the IRB protects research subjects, sometimes to excess. A group of hospitalists at 12 hospitals each sent surveys to 20 local physicians asking which details they would like to find in a discharge summary. That activity required each local investigator to take 3 hours of training on research protections. It also required approval by the local IRBs at each hospital.

In between these extremes, in everyday clinical practice, the primary form of protection is informed consent. Physicians have an obligation to provide the information that a reasonable patient would want to know in order to make a rational decision about embarking on a course of treatment. Failure to provide this is a breach of the standard of care, which means, if the patient suffers harm, they may have a good case for claiming malpractice.

There have been two recent news articles on this subject that caught my eye.

In the Oregon case, a physician denied wrongdoing but agreed in the future to inform his patients that he gets what could be construed as a kickback from the medical supply company for implanting a particular brand of pacemaker.

In the Sacramento case, two neurosurgeons resigned from the University of California, Davis, after a controversy over the inadequacy of research subject protections in their trial of a novel approach for treating a highly malignant brain cancer with "probiotic intracranial therapy," or the introduction of live bowel bacteria, Enterobacter aerogenes, directly into their patients’ brains or bone flaps. The doctors theorized that an infection might stimulate the patients’ immune systems and prolong their lives.

Physicians who use medications for off-label uses are well advised to be sure they are obtaining and documenting informed consent from their patients. Informed consent requires the physician to have provided all relevant details that a reasonable patient would want to know before making a decision. IRBs are in place to protect research subjects. There is a problem, however, with having a higher tier of protection and the associated burdensome paperwork. Powell’s 4th rule of medical ethics: If you raise the bar high enough, people walk under it.

Dr. Powell practices as a hospitalist at SSM Cardinal Glennon Children’s Medical Center in St. Louis. He is associate professor of pediatrics at Saint Louis University. He is also listserv moderator for the AAP Section on Hospital Medicine and is a member of the Law and Bioethics Affinity Group of the American Society for Bioethics and Humanities. He said that he had no financial conflicts of interest. Readers can e-mail Dr. Powell at [email protected].

Years ago, at a departmental meeting, the neurologists informed the general pediatricians that they were going to try out a new therapy for autism. Autism recently had been linked to inflammation of the gastrointestinal system. One of the articles that asserted that link is the now retracted Lancet article by Andrew Wakefield et al., which also falsely linked MMR and autism (Lancet 1998;35:637-41).

At the time, the misrepresentations in that article had not yet been fully revealed.

The treatment the neurologists were considering would utilize the hormone secretin. [Please note that the most recent Cochrane Review in 2012 reaffirmed the 2005 review repudiating this therapy (Cochrane Database Syst. Rev..2012 ;4 [doi: 10.1002/14651858.CD003495.pub3]). However, Mr. Wakefield is still advocating some form of therapy.] Secretin was first isolated in 1902 and has the distinction of being the first hormone isolated by Western science. A synthetic polypeptide analogue has been created. The local neurologists had read about this new therapy for autism and wanted to see if and how it worked. It is not unusual for new therapies to be adopted by subspecialists and then make their way into the armamentarium of general pediatricians. Most drugs I prescribe are not Food and Drug Administration approved in children, but have been adopted for use by other pediatricians and subspecialists.

The aforementioned multispecialty group did not participate in much clinical research. There was an active local institutional review board (IRB). However, in one of the strange paradoxes of medical law, as long as the neurologists were going to haphazardly try the secretin in a few cases, without any scientific control group and without any intention of publishing their results, they were free to do so if, in their professional opinion, they felt the innovative use of the medication might help. I warned them that if they made any attempt to compare results with other patients in an organized, scientific fashion, then IRB approval would be required. I expected that would be very difficult, if not impossible, to obtain.

There is a long and sad history of inadequate protection of research subjects in U.S. medicine. Some protections were put in place in the 1970s. Principles for those protections were outlined in the Belmont Report in 1978. From that report: "When a clinician departs in a significant way from standard or accepted practice, the innovation does not, in and of itself, constitute research. The fact that a procedure is ‘experimental,’ in the sense of new, untested or different, does not automatically place it in the category of research."

And so, we really have a three-tier system. Those who claim to be doing research should be following strict ethical guidelines, using carefully reviewed methodologies, publishing in peer-reviewed journals, and be overseen by the local IRB. The second tier consists of physicians who are taking FDA-approved medications and using them in off-label ways. A medical license grants a physician that right. It is, however, illegal for a pharmaceutical company to detail physicians on these off-label uses. The FDA has cracked down on that recently, including fining Pfizer $2.3 billion 4 years ago. Finally, in the bottom tier, we have late-night infomercials promising for 30 minutes how all these complementary therapies, nutraceuticals, and dietary supplements will make ailments go away while flashing for a few seconds on the screen the disclaimer: "These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease."

People who watch late-night TV are fully availing themselves of their liberty, guaranteed by congressional action, to listen to ridiculous claims unfiltered by the science and conventional wisdom of the medical establishment. At the other extreme, the IRB protects research subjects, sometimes to excess. A group of hospitalists at 12 hospitals each sent surveys to 20 local physicians asking which details they would like to find in a discharge summary. That activity required each local investigator to take 3 hours of training on research protections. It also required approval by the local IRBs at each hospital.

In between these extremes, in everyday clinical practice, the primary form of protection is informed consent. Physicians have an obligation to provide the information that a reasonable patient would want to know in order to make a rational decision about embarking on a course of treatment. Failure to provide this is a breach of the standard of care, which means, if the patient suffers harm, they may have a good case for claiming malpractice.

There have been two recent news articles on this subject that caught my eye.

In the Oregon case, a physician denied wrongdoing but agreed in the future to inform his patients that he gets what could be construed as a kickback from the medical supply company for implanting a particular brand of pacemaker.

In the Sacramento case, two neurosurgeons resigned from the University of California, Davis, after a controversy over the inadequacy of research subject protections in their trial of a novel approach for treating a highly malignant brain cancer with "probiotic intracranial therapy," or the introduction of live bowel bacteria, Enterobacter aerogenes, directly into their patients’ brains or bone flaps. The doctors theorized that an infection might stimulate the patients’ immune systems and prolong their lives.

Physicians who use medications for off-label uses are well advised to be sure they are obtaining and documenting informed consent from their patients. Informed consent requires the physician to have provided all relevant details that a reasonable patient would want to know before making a decision. IRBs are in place to protect research subjects. There is a problem, however, with having a higher tier of protection and the associated burdensome paperwork. Powell’s 4th rule of medical ethics: If you raise the bar high enough, people walk under it.

Dr. Powell practices as a hospitalist at SSM Cardinal Glennon Children’s Medical Center in St. Louis. He is associate professor of pediatrics at Saint Louis University. He is also listserv moderator for the AAP Section on Hospital Medicine and is a member of the Law and Bioethics Affinity Group of the American Society for Bioethics and Humanities. He said that he had no financial conflicts of interest. Readers can e-mail Dr. Powell at [email protected].