美 FDA, 임상실험 감독소홀로 수십만명 위험”<NYT>
연합뉴스 | 기사입력 2007-09-28 17:12
(서울=연합뉴스) 권혜진 기자 = 미국 식품의약청(FDA)이 임상실험에 대한 관리 감독을 등한시해 참가자 수십만명의 안전이 위협받고 있다는 내용의 보고서가 발간될 예정이라고 뉴욕타임스(NYT)가 27일 보도했다.
미 보건부의 대니얼 R. 레빈슨 감독관이 작성한 이 보고서에 따르면 FDA는 임상실험 횟수를 알지 못하는 것은 물론 실험장소의 겨우 1%에 대해서만 감사를 실시하며 이마저도 시험이 이미 종결된 이후에야 방문하는 것으로 나타났다.
보고서는 이어 인체를 대상으로 한 실험에서 심각한 문제점이 발견됐다고 해도 전체 사례의 68%가 위험 수준을 처음보다 낮게 조정한 것으로 드러났다고 주장했다. 또한 나머지 경우에도 절차에 따라 시정 조치가 이뤄졌는지 여부를 추후에 확인하지 않고 있다고 덧붙였다.
펜실베이니아대학의 아서 L. 캐플런 의료윤리학과 학과장은 “오히려 실험용 쥐가 사람보다 더 보호받는 실정”이라고 비판했다.
실제로 동물연구센터의 경우 연방 정부에 시설 신고가 의무화돼 있으며 실험 대상의 수도 매번 기록해야 한다. 또한 불시에 시설 방문이 이뤄지는 것은 물론 문제 발생시 신속히 보고하지 않으면 시설 폐쇄까지 감수해야 한다고 캐플런 학과장은 덧붙였다.
더 큰 문제는 사설 기관에서 이뤄지는 임상실험의 경우 관리 감독이 전혀 이뤄지고 있지 않다는 것.
FDA는 의약품이나 의료 장비의 승인을 추진하는 업체들의 안전성 입증 실험만을 관할하고 있으며, 연방 정부가 출자한 실험은 임상연구안전국(OHRP)이 담당한다. 이로 인해 실험에 적용되는 규칙 또한 매번 달라지는 상황이다. 더군다나 사설단체가 실시하는 비영리적인 실험의 경우 어느 곳의 감독도 받지 않고 있다.
지난 2005년 발생한 오딘 그레이빌 사건이 이러한 체계의 허점을 드러내는 단적인 예라고 신문은 지적했다.
쌍극성 장애를 앓고 있던 그레이빌은 2005년 5월 조울증 치료제의 임상실험에 동의하고 실험 담당자인 데이비드 린든 박사가 운영하는 하이포인트 병원에 입원한다.
그녀가 실험 전 서명한 동의서에 따르면 언제든지 본인의 선택에 따라 중도 포기할 수 있었으나 6월 초 그만두겠다는 의사를 밝혔는데도 불구하고 린든 박사는 퇴원을 허용하지 않았다.
심지어 그녀의 변호사가 법원으로부터 인신보호영장을 발부받아 병원에 가져갔지만 직원들이 이를 무시하고 린든 박사의 소재를 알려주지 않았으며 변호사가 린든 박사를 찾아내 영장을 건넨 끝에 가까스로 퇴원이 이뤄졌다.
FDA는 그러나 이러한 사건이 발생한 지 9개월이 지나서야 린든 박사의 연구센터에 대한 감사를 실시했다고 신문은 밝혔다.
국립보건원(NIH)의 이지키얼 J. 에마누엘 생명윤리학회 회장은 매번 다른 원칙이 적용되는 것은 어불성설이라며 “하나의 기구가 통합해 관리한다면 (관리 감독이) 훨씬 용이해질 것”이라고 주장했다. 재닛 우드콕 FDA 수석 보건소장은 강제력을 강화할 필요가 있다고 강조했다.
FDA에 소속된 조사관의 수는 200여명으로 이들은 미국 내 35만개 실험 장소에 대한 관리감독 의무를 맡고 있다.
lucid@yna.co.kr
(끝)
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Report Assails F.D.A. Oversight of Clinical Trials
By GARDINER HARRIS
Published: September 28, 2007
출처 : New York Times – Sep 27 7:21 PM
http://www.nytimes.com/2007/09/28/health/policy/28fda.html
WASHINGTON, Sept. 27 — The Food and Drug Administration does very little to ensure the safety of the millions of people who participate in clinical trials, a federal investigator has found.
In a report due to be released Friday, the inspector general of the Department of Health and Human Services, Daniel R. Levinson, said federal health officials did not know how many clinical trials were being conducted, audited fewer than 1 percent of the testing sites and, on the rare occasions when inspectors did appear, generally showed up long after the tests had been completed.
The F.D.A. has 200 inspectors, some of whom audit clinical trials part time, to police an estimated 350,000 testing sites. Even when those inspectors found serious problems in human trials, top drug officials in Washington downgraded their findings 68 percent of the time, the report found. Among the remaining cases, the agency almost never followed up with inspections to determine whether the corrective actions that the agency demanded had occurred, the report found.
“In many ways, rats and mice get greater protection as research subjects in the United States than do humans,” said Arthur L. Caplan, chairman of the department of medical ethics at the University of Pennsylvania.
Animal research centers have to register with the federal government, keep track of subject numbers, have unannounced spot inspections and address problems speedily or risk closing, none of which is true in human research, Mr. Caplan said.
Because no one collects the data systematically, there is no way to tell how safe the nation’s clinical research is or ever has been.
The drug agency oversees just the safety of trials by companies seeking approval to sell drugs or devices. Using an entirely different set of rules, the Office for Human Research Protections oversees trials financed by the federal government.
Privately financed noncommercial trials have no federal oversight.
“It’s crazy that we have all these different sets of rules,” said Dr. Ezekiel J. Emanuel, chairman of the bioethics department at the National Institutes of Health. “It would facilitate things a lot if we had one agency overseeing things.”
Dr. Janet Woodcock, chief medical officer at the drug agency, acknowledged that it needs to put more “teeth” in its enforcement. “We are working to address these problems very aggressively,” Dr. Woodcock said.
The case of Audine Graybill demonstrates the flaws in the system. According to the F.D.A., in the spring of 2005, she decided to try an experimental drug to treat mania associated with bipolar disorder. The consent form that she signed on May 29 stated that she could change her mind at any point in the study.
She checked into High Pointe Healthcare in Oklahoma City, a psychiatric center owned by a psychiatrist, Dr. David Linden. On June 3, Ms. Graybill changed her mind and asked to leave.
Dr. Linden refused to let her go.
On June 6, she was given the experimental medicine. Ms. Graybill’s lawyer, Anthony Sykes, obtained a writ of habeas corpus for her to appear in court and took the writ to the hospital, where the staff refused to honor it and said it would not give it to Dr. Linden, Mr. Sykes said.
Mr. Sykes tracked Dr. Linden to another office and had him served with the writ, Mr. Sykes said. Within hours, Dr. Linden’s lawyer called Mr. Sykes and said Ms. Graybill was free to go. Mr. Sykes took her home on June 7.
Ms. Graybill could not be reached.
More than nine months later, an F.D.A. inspector appeared at Dr. Linden’s research center and uncovered myriad other problems.
The agency sent its warning letter more than two years after Ms. Graybill’s experience.
Last November, the Oklahoma Board of Medical Licensure and Supervision suspended Dr. Linden’s license for three months because he had sex with two patients and gave them genital herpes infections, according to board records. Dr. Linden, who also owns a psychiatric center in Las Vegas, did not return repeated telephone messages.
Dr. Linden has conducted clinical trials for most major pharmaceutical companies and continues to do research, according to his Web site.
The F.D.A. disqualified investigators from conducting further clinical trials 26 times from 2000 to 2005 and disqualified their data just twice even though the agency found serious problems at trial sites 348 times in that period, the inspector general found.
While some of the report’s findings surprised ethicists, its conclusion that the agency’s oversight of clinical trials is disorganized and underfinanced has long been known and is, in many ways, identical to criticisms leveled at other agency functions, including its oversight of imported food, foreign drug manufacturers, animal food and the safety of older medicines.
In each case, the size and complexity of the tasks facing the agency have grown enormously as the number of inspectors for those tasks has generally declined.
An inspector general’s report in 2000 criticized the oversight of clinical trials and noted that the inspections mostly focused on whether study information was accurate and not on whether human subjects were protected. That is still true.
In the present report, the inspector general recommended that the agency create a registry of all continuing clinical trials, an idea signed into law by President Bush on Thursday.
The report also recommended that the agency create a complete registry of research ethics boards, create a single comprehensive database to track its research inspections and obtain greater authority to regulate research assistants.
Senator Charles E. Grassley, Republican of Iowa, said the agency “needs to implement these recommendations to meet its duty.”
Representative Rosa DeLauro, Democrat of Connecticut, said it needed more money and guts.
“They’re passive, they’re reactive, and they often side with industry over public health,” Ms. DeLauro said.
The agency’s reserve is apparent in some of its warning letters.
On May 24, 2005, an inspector, Barbara Breithaupt, went to the office of Dr. Frank A. Wingrove of Ames, Iowa, and for weeks asked to see records of his study of an experimental topical treatment for periodontal disease. Dr. Wingrove refused. Dr. Wingrove did not return telephone messages seeking comment.
More than two years later, the agency sent Dr. Wingrove a warning letter. The inspector general’s report suggests that if Dr. Wingrove promised to reform, the agency was unlikely to show up again to see whether he had followed through.
Bigger Is Better, Except When It’s Not
LOOKING back, Dr. Michael Joyner thinks he chose the wrong sport when he became a distance runner. He should have been a swimmer or a rower.
Dr. Joyner, an anesthesiologist and exercise researcher at the Mayo Clinic, was fast — he ran a marathon in 2 hours 25 minutes. But, at 6-foot-5, and 175 pounds at his lightest, he was simply too big to be great.
It turns out that there are rules governed by physics to explain why the best distance runners look so different from the best swimmers or rowers and why being big is beneficial for some sports and not others.
That does not mean that parents should push their children into a sport based on their body type, exercise physiologists say. Most people who run or swim or do other sports, even competitively, do it because they love the sport, not because they are aiming for the Olympic Games. Many also choose a sport because they discover they are good at it.
For example, Dr. Niels H. Secher, an anesthesiologist, exercise researcher and rower at the University of Copenhagen, started rowing when he was 14. He always was big — he weighs 205 pounds — and he immediately loved to row and went with it. “If it works well, you think you are great and you follow up on your success,” he said.
But understanding why body size matters in certain sports can open your eyes to other possibilities, exercise researchers say.
“I’ve told people: ‘You’re tall. Why not try swimming?’” Dr. Joyner said. “Anything worth doing is worth doing well and anything worth keeping a score is worth posting a good score.”
The rules of physics say that distance cycling and distance running are for small people. Rowing and swimming are for people who are big. The physics is so exact that when Dr. Secher tried to predict how fast competitive rowers could go, based only on their sizes and the weights of their boats, he was accurate to within 1 percent.
At first glance, a big rower (and elite male rowers can weigh as much as 250 pounds) may seem to be at a disadvantage trying to row hard enough to push a boat through the water. But because water buoys the boat, weight becomes less of an issue compared with the enormous benefits of having strong muscles.
Their bigger muscles allow bigger people to use more oxygen, giving them more power. It’s like having a bigger motor, Dr. Secher said. Bigger muscles, with their larger cross-section, also are stronger. And bigger muscles can store more glycogen, their fuel for short intense spurts.
The same reasoning explains why elite swimmers are big. Great male swimmers often are 6 feet 4 inches tall, and muscular. And because of the advantage that large muscles give for sprints over short distances, the shorter the distance an athlete must swim, the greater the advantage it is to be big.
Tall swimmers also have another advantage: because swimmers are horizontal in the water, their long bodies give them an automatic edge. “It’s the difference between long canoes and short canoes,” Dr. Joyner said.
Distance running is different. Tall people naturally have longer strides, but stride length, it turns out, does not determine speed. Running requires that you lift your body off the ground with each step, propelling yourself forward. The more you weigh, the harder you have to work to lift your body and the slower you will be.
The best runners are small and light, with slim legs. “If you have large legs, you have to move a big load,” Dr. Secher said. “The smaller you are, the better you are.”
Of course, there are a few exceptions to the scaling rules. There was the Australian runner Derek Clayton, who weighed 160 pounds and set a world marathon mark in 1969.
And there is Tom Fleming (my coach) who won the New York City Marathon in 1973 and 1975. He is 6-foot-1, and while he ran his fastest marathon, 2 hours 12 minutes, weighing 159 pounds, he ran the Boston Marathon in 2 hours 14 minutes weighing 179 pounds. “I tell people that’s the fat-man record of Boston,” he said.
The tallest elite marathoner today, Robert Cheruiyot, is 6-foot-2. But he weighs only 143 pounds. Most elite male marathoners, Dr. Joyner notes, are between 5-foot-7 and 5-foot-11 and weigh between 120 and 140 pounds. In distance running, he said, “you just don’t find many big people.”
The situation is more complicated for triathletes, who must run and cycle and swim. The size that is best for running and cycling is not good for swimming. Yet in general, swimmers have an advantage, Dr. Secher said. It is easier for a great swimmer to learn cycling and running than for a good runner or cyclist to learn to be a good swimmer. Swimming, he says, is so dependent on technique that it is hard to become proficient as an adult.
The decision for high school coaches, said Hayden Smith, a cross-country coach at Albion College, is whether to say anything when a young teenager seems set on the wrong sport. He said he kept mum when he was coaching in high school. But, he added, the best high school athlete he ever coached initially went out for football. The football coach refused to let him join the team — he would not give the boy the equipment.
“He told the kid, ‘You’ll be a great runner,’” Mr. Smith recalled.
The coach was right. The boy started running and ended up one of the top 10 in the nation.
No one ever told Dr. Joyner not to run. Injuries, though, finally forced him to look for another sport. He chose swimming, knowing that his size would be to his advantage.
Dr. Joyner got a coach, worked hard on his technique, and recently ranked 15th swimming a mile in a United States Masters swimming championship race (for people over age 25) . He started too late, he said, to know what he might have been as a swimmer.
But that is O.K., Dr. Joyner said. He loved running. And there is more to performance than simply having the right sort of body for the sport. There is hard work and rigorous training, and, of course, there is motivation.
“I always remember something the late Bill Bowerman said at a clinic I attended in the late 1970s,” he added, referring to the legendary distance running coach. “Sometimes what matters is not what dog is in the fight but how much fight is in the dog.”
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Report Says Smoking Ban Helps to Cut Heart Attacks
By ANTHONY RAMIREZ
Published: September 28, 2007
Government curbs on secondhand smoke in New York led to nearly 4,000 fewer hospital admissions for heart attacks in 2004, according to a new statewide study.
In the study, published yesterday in the American Journal of Public Health, the State Department of Health reviewed nearly half a million hospital admissions for what is known as acute myocardial infarction, or heart attack.
Researchers concluded that such admissions fell more than 8 percent in 2004 from what would have been the expected level of admissions for that year. That was equivalent to 3,813 fewer hospital admissions, they said.
At an average cost of $14,772 for each heart-attack admission, the total savings is about $56.3 million, researchers said.
The 2003 state ban on smoking in many public places is “a public health intervention that hardly costs anything, so to accrue that kind of savings from an inexpensive intervention is really unparalleled,” said Ursula Bauer, the director of the Health Department’s tobacco control program and an author of the study.
The study is more comprehensive than similar studies that covered only a few hospitals in a few counties. It analyzed 10 years of existing data, from 1994 to 2004, covering all of the state’s 62 counties and more than 250 hospitals. It looked at data for admissions for 462,396 heart attacks.
Researchers focused on the year after the July 2003 enactment of the Clean Indoor Air Act, which prohibited smoking in bars, restaurants, banquet halls and places where workers were paid tips or wages.
Using a statistical model incorporating the 10 years of heart-attack data, state health researchers identified factors associated with heart attacks: people suffer more heart attacks in winter; there are different rates in different counties; heart attacks are dropping anyway because of better medical care; and, more important, local governments have been curbing smoking since 1995.
If researchers, in effect, subtract these factors that affect heart attack rates, then what is left is likely to be the effect of the 2003 ban, said Harlan R. Juster, the Health Department’s director of tobacco surveillance, evaluation and research and an author of the study.
By this indirect reasoning, the number of hospital admissions for heart attacks should have been 49,225 for 2004, but was 45,412.
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Genes Tied to Bad Reactions to Antidepressant Drug
By BENEDICT CAREY
Published: September 28, 2007
Variations in two genes may increase the likelihood that a person will report suicidal thoughts after taking an antidepressant, researchers reported yesterday. The finding could help doctors develop tests to predict which patients will do well on such medications and which will react badly.
The authors of the study, which was released to reporters yesterday and will appear in The American Journal of Psychiatry on Monday, said that the findings were preliminary and would need to be verified by further testing.
The study focused on reactions to only one drug, Celexa from Forest Laboratories, and found no link between the gene variations and dangerous behavior like suicide attempts.
This distinction is critical, because doctors do not know whether people who report thoughts of ending their lives are at increased risk to act on them. The one patient in the study who attempted suicide consistently denied having any suicidal thoughts.
The findings come at a time when psychiatrists, regulators and some former patients are locked in a furious debate about the risks of antidepressant drugs, which include products like Prozac from Eli Lilly and Zoloft from Pfizer. In recent years, health regulators have required that drug makers post strong warnings on antidepressant labels, saying that some young patients may be at increased risk of suicidal thoughts and behavior.
Some psychiatrists say the warnings have scared off patients who would benefit from the drugs — based largely on reports of suicidal thinking, which may not increase the risk of suicide itself.
“What I would say is that this study is a wake-up call, that we may have the opportunity to use genomic tests to guide personalized care for depression,” said Dr. Thomas Insel, director of the National Institute of Mental Health, which helped finance the study.
But Dr. Insel added that the genetic test “is not yet ready for prime time.”
The researchers used data from a large government-financed depression study that included more than 4,000 adult patients. They found that about 6 percent of these patients reported having thoughts of suicide after taking the drug, usually within the first few weeks of starting treatment.
They then analyzed blood samples from 120 of those who reported the suicidal thoughts, looking to see whether variations in certain genes were especially common in them.
The scientists found that 36 percent of the patients who had markers for two gene variations reported suicidal thoughts — a more than 10-fold risk compared with those with neither of the gene markers.
These patients were also far less likely to recover taking the drug. Both markers were in genes that affect how the brain processes a chemical messenger called glutamate, which works to activate neurons.
If genetic tests are developed, “they could add to the whole clinical picture,” said Dr. Francis McMahon, chief of the genetics and mood disorders unit of the National Institute of Mental Health and the senior author of the study.
“If a patient tells me he thinks his life is not worth living, or I know he’s at risk of having that reaction, I’m going to monitor him more closely or treat him differently,” Dr. McMahon said.
The researchers searched for links to 68 genes in the patients’ blood samples that might influence mood states, but these are clearly not the only genes that could be involved in the emergence of suicidal thoughts.
Many of the patients who reported a sudden urge to end their lives did not have either of the gene variations found to put people at high risk.