On 10/18/2011, a monitor from Little Rock, Arkansas came today. She was excited when she saw patient’s paper chart. She told me she had been to many clinics; most of them used electronic medical records (EMR).
Nearly all of these electronic system have many problems, either it is not clear where things are, or documents are not available or even worse she is exposed to more data than she is allowed to, which is a violation of HIPPA. Morever, it is difficult for monitors to view patients’ medical records and clinical report on the same laptop.
The EMR is so remotely away from being perfect now. This monitor wished we could all go back to paper eventually, which doesn’t seem likely.
When I asked her if there was a user manual. “None” was the answer. It seems there are so much that needs improvement and that means many opportunities. When we go electronic with our medical records, I will create a user manual especially for the monitors, which will definitely make life easy for all.
From AAAS award speech,
“In 1997, while conducting a clinical trial of a drug that showed promise in improving the lives of patients suffering from thalassemia—a blood disorder that can be fatal if not treated—Dr. Olivieri discovered possibly life-threatening side effects of the medication. She informed the pharmaceutical company, Apotex, of this risk and of her intention to notify the hospital’s Research Ethics Board, her patients, and other clinicians. The company, disagreeing with her findings, informed Dr. Olivieri that such actions would be in violation of a confidentiality agreement she had signed and that they would seek “legal remedies” if she carried out her intentions.”
“After publishing her findings, she suffered a series of adverse actions from the company and the hospital, including being relieved of one of her positions and referral to a physicians’ disciplinary board. The press received anonymous letters accusing her of misconduct, later traced to a colleague who received money from the company. The university where she had an appointment, which had been promised a large donation by the company, supported her only after an investigation by the Canadian Association of University Teachers completely vindicated her, as did the physicians’ board. Dr. Olivieri continues to fight legal battles brought against her by the drug company.”
“Her struggle in defending these principles has brought world attention to the importance of scientific integrity for public health and safety. Editors of leading biomedical journals have imposed new publishing standards, the university changed its policies on industry-supported research, and her findings regarding the drug have stood.”
This case touches many issues related to clinical trials. Do patients have the right to know the truth of the study drug that they are in? Are doctors obligated to be ethical toward patients, even if it means violation of any agreement with the drug company? How much academic freedom is guaranteed when academic institutions have to be sustained by other money?
This is from Scientific American journal, posted on 3/10/2009, with the title “A Medical Madoff: Anesthesiologist Faked Data in 21 Studies — A pioneering anesthesiologist has been implicated in a massive research fraud that has altered the way millions of patients are treated for pain during and after orthopedic surgeries” by Brendan Borrell.
In the course of 12 years, “anesthesiologist Scott Reuben revolutionized the way physicians provide pain relief to patients undergoing orthopedic surgery for everything from torn ligaments to worn-out hips. Now, the profession is in shambles after an investigation revealed that at least 21 of Reuben’s papers were pure fiction, and that the pain drugs he touted in them may have slowed postoperative healing.”
Reuben’s studies led to the sale of billions of dollars worth of the potentially dangerous drugs known as COX2 inhibitors, Pfizer’s Celebrex (celecoxib) and Bextra (valdecoxib) and Merck’s Vioxx (rofecoxib), for applications whose therapeutic benefits are now in question.
Pfizer paid for a clinical study of Dr. Reuben’s on the perioperative use of celecoxib as part of multimodal analgesia for outpatient anterior cruciate ligament reconstructive surgery. Dr. Reuben reported in 2 articles published in the journal Anesthesia & Analgesia that he had treated 200 patients in the trial — 100 with placebo and 100 with celecoxib — and achieved success with multimodal analgesia therapy. However, Dr. Reuben later admitted that he had not enrolled any patients in the trial but, instead, had simply fabricated the findings.
The question that people are likely to ask is why did it take 12 years before a “routine audit” revealed Reuben’s widespread data fabrication? Wasn’t there a red flag somewhere to catch people’s attention to Reuben’s research studies?
That’s why we need auditors, FDA, and whoever have sharp teeth to control, regulate in this lucrative business of research.
The 36-year-old Jolee Mohr, mother of a 5-year-old, was a rheumatoid arthritis patient. She was otherwise young and healthy at the time of her death in 2007. She died three weeks after her participation in a clinical trial with trillions of genetically engineered viruses to ease the pain of rheumatoid arthritis.
To say she died of this clinical trial is like blaming others for our failure. I would rather say two major factors are equally responsible: 1) the therapeutic misconception about clinical trials, that is, the belief that the trial will help her get better without fully understanding that it was only a Phase I study designed to assess toxicity; 2) patient’s failure to read important documents and the risk factors before signing.
When her doctor, Dr. Robert Trapp of the Arthritis Center in Springfield, Illinois told her about the gene therapy study, she had faith in her doctor of seven years. “You trust your physician. He’s your doctor. You trust him like you do your minister,” her husband said. It is your life and you should trust no one but your own research and instinct.
Even worse is the fact that Jolee Mohr signed a 15-page informed consent form (ICF) most probably without reading it and knowing all the risks involved. As her husband put it, “Knowing her, she probably didn’t read through it.”
The ICF warns subjects of “some scary possibilities” of the study. It said that the genetically altered viruses in the study — called tgAAC94 “could spread to other parts of your body. The risks of this are not known at this time… We have seen this type of spread in animal studies when tgAAC94 has been given by injection into the joint,” the form said.
More scary facts include — altered viruses can “damage the DNA in the cells of your body by inserting itself into your genes,” it went on. “If this happens, it could put you at risk for developing cancer in the future.”
And on page 9, it is clearly written that unknown side effects could result in “pain, discomfort, disability or, in rare circumstances, death.”
This informed consent form is an extremely important legal document. By signing on it, you agree to take full responsibility for whatever consequences it forewarns you and thus relieves any duty or responsibility of the other party in case something unexpected happens.
This “rare circumstance” in the form of the tragic death of a young mother is posted here, hoping readers can be wiser than Mohr when they face a similar situation.
The Belmont Report of 1979 is the cornerstone and the foundation behind all of federal rules and regulations governing today’s clinic research, at least according to my understanding.
As a further reaction to Tuskegee Syphilis Study (1932-1972), the then United States Department of Health, Education, and Welfare drafted and passed this report in Belmont Conference Center. That’s how the report got its name. The report attempted to lay out the basic ethical principles and guidelines that should assist in resolving the ethical problems that surround the conduct of research with human subjects. The main idea of this report is RBJ — Respect, Beneficence, and Justice, so much absent in the Tuskegee Study.
Respect for persons –Individuals should be treated as autonomous agents; persons with diminished autonomy are entitled to due protection. No study can be legally carried out without the informed consent of the subjects.
Beneficence –No harmed shall be done to the human subjects. Research should maximize possible benefits and minimize any possible harms. The nature and scope of risks and benefits must be assessed in a systematic manner, so that benefits must be greater than risks.
Justice –The benefits and risks of research must be distributed fairly. The selection and treatment of subjects must be fair and square.
An equally famous or infamous chapter in the history of clinic research is Tuskegee Syphilis Study (1932-1972). It occurred during a research project conducted by the U.S. Public Health Service, where 600 low-income African-American males, 400 of whom were infected with syphilis, were monitored for 40 years.
The participants were given free medical examinations, an incentive to any folks from low-income group; however, they were not told about their disease. Even though a proven cure (penicillin) became available in the 1950s, the study continued until 1972 with participants being denied treatment. In some cases, when subjects were diagnosed as having syphilis by other physicians, researchers intervened to prevent treatment. Many subjects died of syphilis during the study.
The study was stopped in 1973 by the U.S. Department of Health, Education, and Welfare only after its injustice was publicized and it thus became a political embarrassment. In 1974, National Research Act was passed due to the publicity from the Tuskegee Syphilis Study. The Act created the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, which was charged to identify the basic ethical principles that should underlie the conduct of biomedical and behavioral research involving human subjects and to develop guidelines which should be followed to assure that such research is conducted in accordance with those principles.
The Tuskegee Syphilis Study is probably the worst case of unethical human subjects research in the history of the United States. In 1997, under mounting pressure, President Clinton apologized to the study subjects and their families.
It gives one such a warm fuzzy feeling to learn that the protection of human subjects, all of us, constitutes the heart of all the current rules and regulations regarding clinic research. Nearly all of them came into being in response to certain atrocities inflicted against human subjects.
The first and foremost important international document is Nuremberg Code of 1947, developed for the Nuremberg Military Tribunal as standards by which to judge the human experimentation conducted by the infamous Nazis doctors. The Code captures the basic principles of all clinic trials. That is, it is absolutely essential to have voluntary participation and “the voluntary consent of the human subject.” And the “experiment should be so conducted as to avoid all unnecessary physical and mental suffering and injury.”
Further more protection follows. “During the course of the experiment the scientist in charge must be prepared to terminate the experiment at any stage, if he has probable cause to believe, … that a continuation of the experiment is likely to result in injury, disability, or death to the experimental subject.”
In the late 1950s a case involved Thalidomide emphasized the need for more regulation in drug development. Thalidomide was not approved by the FDA, yet it was prescribed to control sleep and nausea throughout pregnancy, but it was soon found that taking this drug during pregnancy caused severe deformities in the fetus. Many patients did not know they were taking a drug that was not approved for use by the FDA. Some 12,000 babies were born with severe deformities due to thalidomide. Thus, the 1962 “Kefauver Amendments” was added to the Food, Drug and Cosmetic Act. It ensures drug efficacy and greater drug safety.
Finally I got over this certification exam yesterday at KUMC, 8 to 12 in the morning. Since I spent so much time preparing for it, I might as well share some of interesting facts here.
When I was toiling through Code of Federal Regulations, I read many extremely tedious and laborious rules on how a clinic research is legally carried out. The regulations are mostly on who does what, how and in what time frame. But it is the theoretical underpinnings for the laying of these rules and regulations that intrique me most. Sometimes, I traced back to the background of the rule establishing and tried to make sense out of it, so that it would not be so intolerably boring. When I do it, it becomes a bit interesting, and then I decide to gradually post some of them here. That’s one of my to-do-items.
Yesterday evening I talked to my mother about my exam and why I wanted to get certified. She was very happy to learn it, saying “It is good that you have a pursuit instead of going about each day just for a paycheck.” She asked me when the result would come out and wanted to be informed as I learned it. Like mother, like daughter. So is it with me and so shall it be with my children. I hope.
For now, I need to get our house ready for another arrival from China, the mother of the 26-year-old relative of ours, coming to visit us next Wednesday. She will participate in her son’s graduation ceremony next Friday, then stay with us for about two months. Looking forward to a lot of back-breaking cleaning work for this weekend.
I studied Code of Federal Regulations on clinic trials and learned that special attention should be given to the problems of clinic research involving vulnerable populations, such as children, prisoners, pregnant women, handicapped, or mentally disabled persons, or economically or educationally disadvantaged persons.
First of all, I used to think of vulnerable populations consisting of children, senior beings, and physically or mentally handicapped beings. I need to digest the fact that being less educated and having less money put one in the category of vulnerability. It makes sense if you think this way — when one does not have money, one is limited in his choice of healthcare or even worse no care at all, and thus he is likely to get into any clinic trials that promise the type of health he cannot afford otherwise. They “are likely to be vulnerable to coersion or undue influence.” So dreadful to be in that situation.
Secondly, I am impressed by the choice of words in CFR, which shows sensitivity toward these groups of social beings. Instead of saying people with mental retardation, we call them mentally disabled. We don’t use the word poor and less educated, we call them “economically or educationally disadvantaged persons.” So cute!