The first controlled medical trial in world history was staged in 1601 by a British ship captain named James Lancaster, reported Professor Ajit Lalvani, head of the Infectious Disease department at the Imperial College Healthcare in London, at the World Health Care conference last month.
Four ships were traveling from England to India around the Cape of Africa, Lalvani explained, when Lancaster decided to give the sailors on his ship three teaspoons of lemon juice every morning. No doubt Lancaster was acting on reports that had come from Sir Richard Hawkins during a voyage to the South Pacific, eight year earlier, when Hawkins had observed that the most effective protection against scurvy appeared to be “sour oranges and lemons.”
As the chart below shows, the hypothesis proved correct: by the end of the voyage, 40 percent of the sailors on the three ships where no one received their Vitamin C had come down with scurvy and perished. On Lancaster’s ship, no one died of the disease.
The medical evidence was compelling, and the British Navy would put it to good use, making sure that all sailors on long voyages received sufficient vitamin C beginning in 1795–194 years after Lancaster’s voyage.
Lalvani, who titled his talk “Translating Evidence into Practice,” used the story to illustrate how long it can take for knowledge about what works and what doesn’t to trickle down into clinical practice.
Today, the problem is even greater, Lalvani pointed out, because the 20th century’s “Age of Information” has turned into this century’s Information Overload. Some call it the Information Bomb. Physicians are bombarded with the never-ending publication of new studies, new numbers and new claims. No one can keep up. One sign of the times: in 2004 the New York Times reported that one session of the American Society of Clinical Oncology’s conference was titled “Therapy of Metastatic Colorectcal Cancer: What Do We Do with So Many Options?”
As each drug company races to fill its own pipeline, a fragmented industry spawns a dizzying array of half-way cures. Too many drugs shrink tumors–but don’t bring any mortality benefit. Meanwhile, too much competition and too little collaboration makes it difficult for oncologists to sort out which drugs are most effective alone, which should be used together–and in what sequence.
But it is not just the drug industry that is fragmented. As Lalvani noted, specialists practice in separate silos, and important information often doesn’t make it from one silo to the next.
The task of consolidating, analyzing and synthesizing what we know should be high on the 21st century’s agenda. But too many researchers are overwhelmed by the tsunami of new claims–and no one is setting comprehensive standards for “best practice” in many areas where we do, in fact, know what constitutes effective treatment.
Here Lalvani quoted Sir Muir Grays, the Director of England’s National Knowledge Service, National Screening Service, and National Health Service:
“The appropriate application of what we already know about the diagnosis and treatment of disease will have a far greater impact on quality and safety than any new medical technology likely to be developed in the next decade.”
Indeed, “despite amazing new technologies,” doctors often don’t practice the basics, Lalvani warned, displaying a chart taken from a study published in the New England Journal of Medicine in 2006.
The study revealed that, on average, only 55 percent of patients get the basic “gold standard” of care that we know that they should be getting for those conditions listed on the left side of the chart. It turns out that the share of patients getting the “right care at the right time” varies widely depending on the disease.
For example, within Lalvani’s studied population, patients with senile cataracts received 78.7 percent of the care they should receive, but those suffering from alcohol dependence received only 10.5 percent of the care that the best research on alcoholism recommends. These are not areas where there is a lot of ambiguity: we have the information; we know what treatment these patients require. But translating medical evidence into practice is something else.
Indeed, just 24 percent of diabetics participating in the study received three or more glycosylated hemoglobin tests over a two-year period, even though “this routine monitoring is essential to the assessment of the effectiveness of treatment . . . and to the identification of complications of the disease at an early stage so that serious consequences may be prevented.”
Overall, patients suffering from coronary artery diseases received 68 percent of the care specialists recommend, but only 45 percent of those who had heart attacks received the simplest treatment–beta-blockers–even though we know that these drugs reduce the risk of death by 13 percent during the first week of treatment and by 23 percent over the long term. Only 61 percent of heart attack patients who can tolerate aspirin were given the pill–despite the fact that randomized trials have shown that this simple measure can reduce the risk of nonfatal stroke by 40 percent.
Why so much slippage? Patients don’t get recommended care in part because physicians are so busy, in part because these days, patients are often treated by four or five different doctors–and each may think that someone else gave the aspirin. Finally, research shows that these things happen in our most sophisticated academic medical centers, where everyone is so busy keeping up with an embarrassment of new technologies, tests and medications that, too often, they forget the basics.
“The gap between what we know works and what is actually done is substantial enough to warrant attention,” the NEJM study concluded.
“What can we do to break through this impasse?” the researchers asked. “Given the complexity and diversity of the health care system, there will be no simple solution. A key component of any solution, however, is…to make information available…with a focus on automating the entry and retrieval of key data for clinical decision making and for the measurement and reporting of quality.” In other words, we desperately need electronic medical records, and the data from those records needs to be consolidated in order to establish benchmarks for performance and best practice guidelines.
But even the best healthcare information technology will not help if physicians resist the fact that medical knowledge is constantly changing, Lalvani points out. Too often, physicians stick to the treatments they have always used, declaring that if tens of thousands of physicians do it this way, it must work. (This doctrine helps explain why, for so long, doctors continued to perform tonsillectomies on half of the children who crossed their paths–and why today, so many resist the notion that statins may be over-prescribed. Understandably, some physicians have a very hard time accepting that what they have been doing for many years is simply wrong–and may have been hurting patients).
Here again, Lalvani turned to history to make his point, telling the sad story of Dr. Ignaz Philipp Semmelweis, who practiced obstetrics at the University of Vienna in 1847.
There, Semmelweis observed that a large percentage of women giving birth were dying of “childbed (puerperal) fever.” Moreover, he noticed that 13 percent to 18 percent of the women whose babies were delivered by physicians or medical students succumbed to the fever, while only 2 percent of those delivered by midwives or trainees died in this way.
Semmelweis then put these facts together with another observation: the doctors and medical students often handled cadavers, and didn’t wash their hands before turning to help the women in labor. He made the obvious suggestion–and was rebuffed.
Mandatory hand-washing would be too difficult, the other physicians groused. It would require installing new plumbing. Anyway, that couldn’t be the problem–it must be poor ventilation. (In fact, hand-washing would have reduced mortalities to just two percent of the women.)
The other physicians were, in fact, so annoyed by Semmelweis’ impertinence that he lost his teaching privileges at the Vienna hospital.
Two years later, his assistant professorship was not renewed. He fled Vienna and returned to Budapest, jobless. About 5 years later he died in a public insane asylum at the age of 47.
But, I couldn’t help but wonder, could something like this really happen today?
Lalvani was ready with an example. 150 years later, he pointed out, Barry Marshall and Robin Warren published seminal research in the British medical journal Lancet, suggesting that peptic ulcer disease is caused by Helicobacter pylori, a bacterium that thrives in acidic environments, such as the stomach.
At the time, the conventional wisdom was that excess stomach acid and emotional stress caused ulcers. Practitioners of gastroenterology and the pharmaceutical industry were both heavily invested in the belief that such ulcers could only be treated with repeated courses of antacid medication. And in fact, reducing the levels of stomach acid often seemed to cure the existing ulcer. But inflammation of the stomach lining usually persisted. Most patients found themselves returning in a year or two with another ulcer. Often, they were advised to seek psychiatric counseling, find less demanding employment or make other drastic lifestyle changes to address the stress that was causing their disease.
“In this environment, the possibility that the ailment was directly caused by a single microorganism that could be completely eliminated with a two-week course of antibiotics was a threat to the status quo,” the Academy of Achievement later reported. “While many of Marshall’s critics had serious scientific questions about his hypothesis, others may have had economic motives in disputing his findings, and Marshall was not shy about saying so. The targets of his criticism soon sought to discredit him and his research. One prominent gastroenterologist dismissed him as “‘a crazy guy saying crazy things.'”
It was not until 1994, when patents for acid reducing drugs were expiring, that a conference held by the National Institute of Health demonstrated the general acceptance of H. pylori as the cause of peptic ulcers in the US. The strongest financial motives for disputing the medical evidence had now disappeared.
In the end, Marshall and Warren fared far better than poor Semmelweiss. In 2005, they were awarded the Nobel Prize in Physiology or Medicine. Nevertheless, countless patients had undergone unnecessary suffering and pointless treatments during the many years that so many doctors resisted assimilating the new evidence.
“Semmelweis went insane trying to change physician behavior,” Lalvani observes, and things have not changed so much since then. “Too often, egos prevail, or worse, personal economic interests carry the day. Some doctors will argue that it is simply unreasonable to think that physicians cause disease.”
So today, many doctors still resist hard evidence that they should change the way they practice medicine. Just as Semmelweis’ colleagues argued that it would be too costly to install new plumbing, many physicians argue that health care information technology is simply too expensive, or that establishing benchmarks for best practice for all clinical processes is just “too much work”–“Let’s just focus on few,” they say.
Some reject medical evidence simply by saying “we do it differently here.”
At the same time, Lalvani acknowledged, these days, with so many new studies coming out, it is impossible, even with the best of intentions, to assimilate all of the new research, and to sort out what is true, and what isn’t.
Still, Lavlani ended his talk by stressing the difference between “Evidence Based Medicine” and “Eminence Based Medicine.”
“Eminence Based Medicine means repeating the same mistakes with increasing confidence over an impressive number of years,” he explained, quoting the BMJ. By contrast, “The practice of evidence-based medicine involves integrating individual clinical expertise with the best available external clinical evidence from systematic research.”
“When doctors in Israel took industrial action and went on strike back in 2000, it highlighted a strange phenomenon – when doctors go on strike, the death
rate plummets.”
http://www.thetruthseeker.co.uk/article.asp?ID=6532
Semmelweis wasn’t the only such victim, although the fates of various inventors of general anesthesia may have been an early warning of too much commercialization in medicine.
I wonder if EBM would include something like the case of Dr. Ephraim McDowell, who was the first to successfully remove an ovarian tumor, before anesthesia or antisepsis. His patient distracted herself from the pain by singing hymns.
The crowd outside had a noose dangling from a branch, for McDowell, if his patient died. Ironically, he himself probably died of appendicitis, the surgery for which was much less invasive.
Some of this may be American culture, thinking of the friend I used to counsel, “Don’t just do something. Sit there.”
A complex set of rewards is operating here. It’s interesting that you mention the deserved Nobel Prize to Marshall and Warren, which was one of the first, in recent memory, for clinical rather than basic research. The Lasker Awards were set up to be a clinical equivalent.
Of the “gold standard” chart, for how many of the interventions that received the appropriate care was the treatment a well-defined procedure, rather than a long and often frustrating process such as treatment or alcoholism, or rehabilitation (not just fixation) of hip fractures?
It’s one thing to establish a standard of care in randomized controlled trials, but another matter to establish the best community treatment, in the presence of comorbidities or social factors that might exclude someone from RCTs. This is another reason to look, again, at the quality improvement mechanisms in German medicine. It’s also an argument for appropriately safeguarded electronic health records, so there is an understanding of what does and does not work in primary care. Of course, the latter would be confounded by inability to pay and get continuity of care.
*sigh* I will have an interesting time in the morning, on something that might or might not be EBM. I’m seeing a specialist in one large practice after firing the first for several reasons, but, above all, severe and emergent inability to listen to me. Perhaps her successor will be better, given the correspondence that will greet her.
And let us not forget E.A. Codman who in the early 20th Century (1910) promoted the ‘end results idea’to ascertain whether or not treatments were successful. His ideas were rejected by his peers at the Mass. General Hosp, particularly when the tenured professors were shown to have poorer results than their subordinates!
I was drawn to this article by the mention of Semmelweis, as I reference the Semmelweis Reflex in my author squib at the end of my story in the May Nature Physics. I thought he and his Reflex had been largely forgotten.
The Simmelweis Reflex, by the way, is tendency of established scientists to automatically reject new evidence. He may have died in an insane asylum, but at least he got a Reflex named after him – of course, most people have never heard of it. Someone asked if it is like the Heimlich Manuever, to which I responded, actually, it is – a self-Heimlich.
Ignaz Semmelweis is labeled “insane” by his fellow doctors for having the audacity to suggest that doctors should wash their hands between delivering babies. He’s vindicated long after his death when it is realized that, indeed, infections are spread from one patient to another by physicians and other health care workers who are too lazy, stubborn or egoistic to simply wash their hands. A lack of hand washing continues to be the primary reason why MRSA and other superbugs are spread in hospitals and nursing homes today.
Drs. Marshall and Warren proving, partly by accident, that uclers of the stomach and intestine are not caused by stress, spicy foods, or even cigarettes and alcohol, but rather by a bacterium. Single handedly they got rid of both the number one surgical operation and the largest part of the market for the number one drugs, dealing a huge blow to both big surgery and big pharma, and making the lives of tens of millions much more pain free and enjoyable. It was done without any research grants and over the dead body opposition of the entire world of medicine, gastroenterology, surgery, the NIH, and the pharmaceutical industry. And one was used as the definitive guinea pig.
We would all like to think that organizations, government agencies, scientists, researchers, and even practitioners work together, sharing information for the benefit of patients. However, each group has its own priorities and its own agenda. Moreover, the image of cooperation between these very different groups only gives the illusion that reform isn’t needed. The present system exists to serve academic achievement and publication, but not to serve the best interests of patients.
A perfect example of thirty-five years of the trail-and-error mind-set that has occupied research. The “investigator” culture that prizes itself on the exhaustive examination of trivial hypotheses, while eschewing support of “discoverer” type research, attempting to create entirely new paradigms of treatment. A dysfunctional culture that pushes tens of thousands of physicians and scientists toward the goal of finding the tiniest improvements in treatment rather than genuine breakthroughs, that rewards academic achievement and publication over all else.
Many bio-medical scientists and medical practitioners unfortunately actually deify their veiws not unlike those who hold dogmatic rigid religious beliefs.
This rididity is especially apparant when the new science doesn’t fit into the prevailing scientific paradigms.
There is an entire body of literature on this resistance phenomenom usually, in my opinion, born out of fear at best or greed and power at worst.
Dr.Rick Lippin
Southampton,Pa
Maggie,
I think you may have picked a poor example for the first medically controlled trial because the conclusions reached and propagated for so many years have not been proven.
The medical evidence was compelling, and the British Navy would put it to good use, making sure that all sailors on long voyages received sufficient vitamin C beginning in 1795–194 years after Lancaster’s voyage.
What had been demonstrated, people say, is that scurvy is a “dietary deficiency resulting from lack of fresh fruit and vegetables.” Nutritionists assumed that these foods are an absolutely essential dietary source of vitamin C.
“. . .however, James Lind and the nutritionists who followed him in the study of scurvy demonstrated only that the disease is a dietary deficiency that can be cured by the addition of fresh fruits and vegetables. As a matter of logic, though, this doesn’t necessarily imply that the lack of vitamin C is caused by the lack of fresh fruits and vegetables. It’s possible that eating easily digestible carbohydrates and sugars increases our need for vitamins that we would otherwise derive from animal products in sufficient quantities.” There is too much information for me to type here so I will point you to my source: Good Calories, Bad Calories, Gary Taubes, pp 320 to 326.
I loved this blog and the comments! A few points of interest:
• ‘The appropriate application of what we already know…’ is probably hampered by the physician not being able to accurately assess what’s going on with the patient, based on insurance payment requirements and restrictions, per appointment.
• Practicing the ‘gold standard of care’ would require payment for same. Unless it’s WC, it probably won’t be approved…
• And, my favorite new knowledge out of this includes the Semmelweis Reflex and Eminence-based medicine – I may frame them for my wall…
On a more serious note, I think it’s deplorable that the excuse is proposed that busy physicians, and those who may work as part of a medical team in the treatment of a single patient, forget that their first responsibility is supposed to be to get it right for the patient! In those instances, ‘busy’ should translate into ‘lawsuit’ – and I’m not normally of a litigious mind! I propose a new UM structure to mandate that appropriate care be offered to the patient – what a novel idea!
Eminence vs evidence-based medicine
Or why it’s so hard to change the way doctors practice medicine.
“Indeed, just 24 percent of diabetics participating in the study received three or more glycosylated hemoglobin tests over a two-year period, even though “this routine monitoring is essential to the assessment of the effectiveness of treatment . . . and to the identification of complications of the disease at an early stage so that serious consequences may be prevented.” ”
2 points:
1. I had 4 diabetic visits in clinic the other day. 2 of the 4 know they are supposed to come in more than yearly for their exam/labs. They don’t because they are generally controlled and don’t like coming to the doctor. I have absolutely nothing to do with that decision on their part. And it’s not a completely irrational decision, though I do strongly encourage at least 2x/year visits and labs for them.
2. The dogma that tightly controlling A1Cs in Type II diabetics with multiple meds/frquent visits/insulin regimens does anything clinically meaningful with regard to patient outcomes has limited to zero evidence supporting it. (This is an evidence based post and discussion after all.)
just giving some perspective here.
Physicians aren’t unique in our resistance to evidence and change. Just human. Merely normal human behavior.
I would love to see evidence to the contrary. That is why I so looked forward to Dr. Groopman’s “How Docs Think”…No evidence for any special thought skills or flexibility there, despite the presumptive title.
What IS unique about physicians is our position in society. We have been assigned authority up there with priests.
Come to think of it, the clergy isn’t famous for changing behavior either…Despite their significantly structured authority.
Why should docs change behavior? What we do now is “working”…That is, maintaining our power and position. I have yet to see a state drop licensing requirements, consider breaking the monopoly…
Oh, you were talking about health…Is THAT what we do?
Thank you all for comments.
Beginning from the top-
ddx:dx– Good comment!
pcb–since you are a doctor, and I’m not, I’m inclined to take your word for it that in this instance the recommended care for diabetics may well be over-rated.
But speaking to the larger point, the author’s idea is that assuming the check-ups are needed, we need a better structure to bring patients in–maybe reminder calls from nurse-practioners who can talk to them about why it’s important?
Also in the U.K. there is no payment at point of service, so a reluctance to make a co-pay or meet a deductible doesn’t keep them home. It would be good if we could get rid of co-pays and deductibles for stuff that we know works in preventive care and chronic disease management. Pitney Bowes has done that for its employees–with significant success.
deb –I agree the fact that doctors are “busy” doesn’t sound like much of an excuse.On the other hand, if you’ve been in a hospital lately, things can be pretty chaotic.
And when several doctors are treating one patient, it’s easy to see how one would assume that someone else had done something–especially since, in most cases, we don’t have electronic medical records.
(If every doctor had a laptop, with the EMR for all patients on it, the way they do at the VA, then he could quickly check to see if someone had given the aspirin . . )
mike– I take your point. What they need is fresh fruits and vegetables–not everyone is sure vitamin C is the key.
Dr. Rick–I’m afraid you’re right. . . .
Gregory — I agree with everything you say, except when you write: “The “investigator” culture that prizes itself on the exhaustive examination of trivial hypotheses, while eschewing support of “discoverer” type research, attempting to create entirely new paradigms of treatment.”
It’s not that I disagree, I just don’t understand: what is the difference between “investigator” reserach and “disoverer” research?
Jeff C writes: “He may have died in an insane asylum, but at least he got a Reflex named after him – of course, most people have never heard of it. Someone asked if it is like the Heimlich Manuever, to which I responded, actually, it is – a self-Heimlich.”
Great comment. (But I still feel very sorry for Semelweiss)
Jonathan– I guess Codman was trying to pioneer “outcomes research.”
Howard: YOu write: “Of the “gold standard” chart, for how many of the interventions that received the appropriate care was the treatment a well-defined procedure, rather than a long and often frustrating process such as treatment or alcoholism, or rehabilitation (not just fixation) of hip fractures?”
This is a good point. We’re really don’t have sure-fire treatments for alcoholics–it’s hard to keep them on the meds that will keep them from drinking, and it just seems much more complicated than nicotine addiction. AA works for some people, but not all.
Jeff– that it truly depressing. Of course some of it is just that patients didn’t die in surgery during the strike because they didn’t have surgery.
But after it was over, presumably many would still die either because they didn’t have needed surgery, or because they were too frail to withstand it.
Nevertheless, much medical care does, inadvertently, cause iatrogenic disease (disease caused by the care) . .
According to Dana Farber’s Emil Frey, who elaborated on this division many years ago, the “discoverer” is a risk taker, not so well organized, high failure rate, but big payoff when successful. The “investigator” culture has no risk taking, has well organized, exhaustive analysis of trivial hypotheses, with minuscule payoff when successful.
Gregory–
Not so surprising, I
tend to always like the risk-takers.
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I’m guessing that ‘Lalvani’, ‘Lavani’, ‘Lavlani’, and ‘Lavanali’ are the same person?? 🙂
Nice Article, BTW.
S. Aloxin Botemill wrote:
I’m guessing that ‘Lalvani’, ‘Lavani’, ‘Lavlani’, and ‘Lavanali’ are the same person?? 🙂
Nice Article, BTW.”
Okay, okay, so I type a little fast. But someone else does the proof-reading . . . Still, the responsibility stops here.
Thanks for the kind words at the end.
Posted by: S. Aloxin Botemill
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First, a historical note: UCLA did a survey of the greatest physicians of all time. John Snow was #2. While I would have some other contenders, how many nonspecialists recognize the name and the significance of the Broad Street Pump, to say nothing of his other innovations? As an aside, some documents that have come to light recently suggest that Snow and Florence Nightingale independently started using statistics as a tool of preventive medicine.
Apropos of A1C control, there’s a damned if you do, damned if you don’t situation. Do we have anything else that is particularly predictive of diabetic complications, without actually being a complication? I can argue both ways about microalbumin levels.
A1C isn’t unique as a surrogate marker, although there’s more molecular justification on its significance than with several other markers. What’s the right approach?
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One usually has to wait until three AM to get an infomercial for Agora Health Newsletters. Thanks to Jeff, I can go to sleep at a reasonable hour.
Evidence-based medicine is good for establishing guidelines for clinical problems. The devil’s in the details, however, as there are those pesky patients who haven’t read the latest metanalysis. In those cases, we rely on physicians to take a page out of the US Marines’ playbook – Improvise, Adapt, Overcome.
Then, there are those pesky lawyers who’ve doubtless added to the wasted expenditures on tests, procedures and consults which serve more to protect the chart than to protect the patient.
Finally, there are those ubiquitous MCO’s who continue to lower the limbo bar of reimbursement and delay authorizations for treatment.
We are certainly living in “Interesting Times.”
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“The first controlled medical trial in world history”:
Daniel 1:5 to 1:19.
The key ingredient has an unspecific meaning, and is often translated as either ‘vegetables’ or ‘grains.’ I believe the original meaning of the key ingredient is a word that means ‘gathered food,’ which might include grains, legumes, and/or vegetables. King James has ‘pulse,’ which is supposed to be a term for ‘vegetables.’ Either way, any or all of these are healthy alternatives.
You mention over-enthusiastic tonsillectomy by doctors in the past. Well, maybe. But that’s from a modern perspective, when we have effective antibiotic treatment. Before penicillin was discovered (in the 1940’s – within living memory) the operation was much more commonly advised, and with good reason. Complications of tonsil infections were serious, including death from abscess formation and rheumatic heart disease. As we get increasing antibiotic resistance, and as we begin to rediscover the importance of biofilms (the modern take on focal sepsis) it is quite likely that tonsillectomy rates will increase. I’m an ENT specialist with longstanding interests in both Evidence Based Medicine and medical history. Both can teach us a lot. One thing that we should certainly learn is that what we think is right today will probably be wrong tomorrow, but then it will come round again…
If you want to see the Semmelweis Reflex at work in contemporary medicine you need only read the current dermatological papers on ‘Delusions of Parasitosis’. Particularly in the context of the Mayo Clinics statements about ‘Morgellons Disease’ and the CDC’s investigation of what they provisional name ‘Unexplained Dermopathy.
To see a contemporary example of medical/scientific resistance to change and its human consequences you need go no further.
Although unstated, I can’t help thinking Semmelweis’s Reflex and the Morgellons Disease phenomenon for that matter, have much to offer the philosophy of medical ethics.
Frankly, I have heard about this case but I never knew what was the story all about. Now, things are pretty clear. Thank you very much for the information you have provided us with.
“When doctors in Israel took industrial action and went on strike back in 2000, it highlighted a strange phenomenon – when doctors go on strike, the death
rate plummets.”