May 12, 2010
Ethics in Medical Research
John Glod, MD, PhD
Robert Wood Johnson Medical School
Minutes of the 32nd Meeting of the 68th Year
President George Hansen opened the meeting at 10:15 AM in the Convocation Room of the Friends Center. Don Edwards led the invocation. The May 5th meeting minutes were presented by Art Eschenlauer. Jack Reilly conducted the election of new Old Guard members.
The following were voted in as members:
Patricia Marks, Charles Plohn, Edward Gayner, Robert Vichnevetsky, Robert Williams, Frank Henschel, Jean Mahoney, Julius Richter, Terry Grabar, Robert Comizzoli, Dick Scribner, Mitchell Seltzer, Marue Wallizer, and Rosemary Walmsley.
Doctor John Glod was introduced by the President. Dr Glod is a Pennsylvania native whose 19 years of training included a BS in Biochemistry from Lehigh, an MD/Ph.D. from the University of Colorado, a Pediatric Residency at Cincinnati Children’s Hospital, and three fellowships one in Cincinnati, the second at Johns Hopkins, and the third at the National Institutes of Health in Bethesda, Maryland. He is presently at Robert Wood Johnson Medical School and the Cancer Institute of New Jersey as an Assistant Professor of Pediatrics and Pharmacology in the Division of Pediatric Hematology and Oncology.
His talk was titled, “Ethics in Medical Research.”
Dr. Glod began by asking the Question, “Why do medical research?” He answered with “The goal of research is to develop new therapies, and improve outcomes for our patients.” Next he discussed the three phases of medical research. Phase one is done on a few volunteers looking at effects, good or bad, the drug has on humans. Phase two is conducted on a limited number of patients to determine what effect the drug has on a particular disease. And Phase three is conducted on a large number of patients to determine if it is better than no therapy or is better than the current standard of care.
Dr Glod outlined the history of clinical trials beginning with Herophilus who lived between 335 to 280 BC. Herophilus, using the scientific inquiry of dissection, recognized the brain as the center of the nervous system, described arteries and veins and variations in pulse rates.
Next the Afghanistan Persian, Avicenna (980-1037 AD), introduced the scientific method and wrote the Cannons of Medicine, a text book that became the foundation for western medicine for hundreds of years.
It was Dr James Lind, who conducted the first controlled experiment on British sailors discovering the treatment of scurvy.
Later Dr Edward Jenner observed that vaccination with cowpox pus prevented smallpox.
Major Walter Reed first used an Informed Consent Document signed by volunteers participating in his Cuba yellow fever studies.
Lastly he described Dr. Sigmund Rascher's experiments conducted in a Nazi concentration camp, the results of which remained in the medical literature well into the 1960’s. It was Dr Rasher’s studies that led to the Nuremberg Codes. These are the first written rules for how to do medical research. These rules were further defined in the Declaration of Helsinki establishing the rule that unethical research could not be accepted for publication. Helsinki established the rights of the individual, to self determination, to be informed and the codification of the needs of society. It identified special groups to be protected such as children and prisoners. The need for this protection is illustrated by the US Public Health Service Tuskegee Syphilis Study. It was conducted from 1931 to 1972 on black men to determine the natural history of the disease. The study’s problems were it did not represent the general population, did not get informed consent and was continued for years after a cure for the disease had been discovered. The study was exposed by the lay press, not the medical profession.
As a result, the Belmont Report came out establishing three principles, the principle of respect, the principle of beneficence and the principle of justice. The principle of respect treats each individual as an autonomous agent and those persons with diminished autonomy are entitled to protection. The principle of beneficence protects patients from harm along with efforts to secure their well being. The principle of justice states the study’s burden should be borne by all parts of the population. If the research is to benefit the entire population, than trials should be designed to include all parts of the population. That includes women and children.
In 1966, Dr Henry K. Beecher published an article in the New England Journal of Medicine titled “Ethics and Medical Research.” He surveyed many ongoing medical research projects and found 22 that he considered unethical. This land mark article influenced the findings of the Belmont Report and a direction to the refereed Medical Journals that results of unethical research should not be published.
Dr. Glod then said “now that I’ve told you all the bad things about clinical research, let me tell why it is ethically imperative we do clinical trials.”
One, we are not really that smart implying what we now know is only a fraction of what is to be learned.
Two, if done correctly, a clinical trial provides the best care for the patient. An example of what happens when it is not done correctly was the use of bone marrow transplant in the treatment of breast cancer. It was promising on a very few phase two trial patients. Unfortunately a phase three trial was not done and it became accepted as the standard of care without going through a true well constructed complete clinical trial. It took years before further research showed large groups of phase three patients did not do better with this treatment, in fact they did worse.
In contrast acute leukemia in children, that was uniformly fatal 60 years ago, now has survival rates in the 90th percentile, all because pediatricians strictly adhered to protocols in clinical trials. He concluded that “Great science cannot happen in isolation of ethical behavior.
A lively question and answer period followed and the meeting was concluded at 11:30.
Respectfully submitted,
George Hansen
The following were voted in as members:
Patricia Marks, Charles Plohn, Edward Gayner, Robert Vichnevetsky, Robert Williams, Frank Henschel, Jean Mahoney, Julius Richter, Terry Grabar, Robert Comizzoli, Dick Scribner, Mitchell Seltzer, Marue Wallizer, and Rosemary Walmsley.
Doctor John Glod was introduced by the President. Dr Glod is a Pennsylvania native whose 19 years of training included a BS in Biochemistry from Lehigh, an MD/Ph.D. from the University of Colorado, a Pediatric Residency at Cincinnati Children’s Hospital, and three fellowships one in Cincinnati, the second at Johns Hopkins, and the third at the National Institutes of Health in Bethesda, Maryland. He is presently at Robert Wood Johnson Medical School and the Cancer Institute of New Jersey as an Assistant Professor of Pediatrics and Pharmacology in the Division of Pediatric Hematology and Oncology.
His talk was titled, “Ethics in Medical Research.”
Dr. Glod began by asking the Question, “Why do medical research?” He answered with “The goal of research is to develop new therapies, and improve outcomes for our patients.” Next he discussed the three phases of medical research. Phase one is done on a few volunteers looking at effects, good or bad, the drug has on humans. Phase two is conducted on a limited number of patients to determine what effect the drug has on a particular disease. And Phase three is conducted on a large number of patients to determine if it is better than no therapy or is better than the current standard of care.
Dr Glod outlined the history of clinical trials beginning with Herophilus who lived between 335 to 280 BC. Herophilus, using the scientific inquiry of dissection, recognized the brain as the center of the nervous system, described arteries and veins and variations in pulse rates.
Next the Afghanistan Persian, Avicenna (980-1037 AD), introduced the scientific method and wrote the Cannons of Medicine, a text book that became the foundation for western medicine for hundreds of years.
It was Dr James Lind, who conducted the first controlled experiment on British sailors discovering the treatment of scurvy.
Later Dr Edward Jenner observed that vaccination with cowpox pus prevented smallpox.
Major Walter Reed first used an Informed Consent Document signed by volunteers participating in his Cuba yellow fever studies.
Lastly he described Dr. Sigmund Rascher's experiments conducted in a Nazi concentration camp, the results of which remained in the medical literature well into the 1960’s. It was Dr Rasher’s studies that led to the Nuremberg Codes. These are the first written rules for how to do medical research. These rules were further defined in the Declaration of Helsinki establishing the rule that unethical research could not be accepted for publication. Helsinki established the rights of the individual, to self determination, to be informed and the codification of the needs of society. It identified special groups to be protected such as children and prisoners. The need for this protection is illustrated by the US Public Health Service Tuskegee Syphilis Study. It was conducted from 1931 to 1972 on black men to determine the natural history of the disease. The study’s problems were it did not represent the general population, did not get informed consent and was continued for years after a cure for the disease had been discovered. The study was exposed by the lay press, not the medical profession.
As a result, the Belmont Report came out establishing three principles, the principle of respect, the principle of beneficence and the principle of justice. The principle of respect treats each individual as an autonomous agent and those persons with diminished autonomy are entitled to protection. The principle of beneficence protects patients from harm along with efforts to secure their well being. The principle of justice states the study’s burden should be borne by all parts of the population. If the research is to benefit the entire population, than trials should be designed to include all parts of the population. That includes women and children.
In 1966, Dr Henry K. Beecher published an article in the New England Journal of Medicine titled “Ethics and Medical Research.” He surveyed many ongoing medical research projects and found 22 that he considered unethical. This land mark article influenced the findings of the Belmont Report and a direction to the refereed Medical Journals that results of unethical research should not be published.
Dr. Glod then said “now that I’ve told you all the bad things about clinical research, let me tell why it is ethically imperative we do clinical trials.”
One, we are not really that smart implying what we now know is only a fraction of what is to be learned.
Two, if done correctly, a clinical trial provides the best care for the patient. An example of what happens when it is not done correctly was the use of bone marrow transplant in the treatment of breast cancer. It was promising on a very few phase two trial patients. Unfortunately a phase three trial was not done and it became accepted as the standard of care without going through a true well constructed complete clinical trial. It took years before further research showed large groups of phase three patients did not do better with this treatment, in fact they did worse.
In contrast acute leukemia in children, that was uniformly fatal 60 years ago, now has survival rates in the 90th percentile, all because pediatricians strictly adhered to protocols in clinical trials. He concluded that “Great science cannot happen in isolation of ethical behavior.
A lively question and answer period followed and the meeting was concluded at 11:30.
Respectfully submitted,
George Hansen