Category: Methodology

Double-Blind Clinical Trials Are NOT the Only Source of Good Evidence

(p. 16) Back in her office, . . . [rheumatologist Jennifer Frankovich] found that the scientific literature had no studies on patients like this to guide her. So she did something unusual: She searched a database of all the lupus patients the hospital had seen over the previous five years, singling out those whose symptoms matched her patient’s, and ran an analysis to see whether they had developed blood clots. “I did some very simple statistics and brought the data to everybody that I had met with that morning,” she says. The change in attitude was striking. “It was very clear, based on the database, that she could be at an increased risk for a clot.”
The girl was given the drug, and she did not develop a clot. “At the end of the day, we don’t know whether it was the right decision,” says Chris Longhurst, a pediatrician and the chief medical information officer at Stanford Children’s Health, who is a colleague of Frankovich’s. But they felt that it was the best they could do with the limited information they had.
A large, costly and time-consuming clinical trial with proper controls might someday prove Frankovich’s hypothesis correct. But large, costly and time-consuming clinical trials are rarely carried out for uncommon complications of this sort. In the absence of such focused research, doctors and scientists are increasingly dipping into enormous troves of data that already exist — namely the aggregated medical records of thousands or even millions of patients to uncover patterns that might help steer care.
. . .
(p. 17) . . . , developing a “learning health system” — one that can incorporate lessons from its own activities in real time — remains tantalizing to researchers. Stefan Thurner, a professor of complexity studies at the Medical University of Vienna, and his researcher, Peter Klimek, are working with a database of millions of people’s health-insurance claims, building networks of relationships among diseases. As they fill in the network with known connections and new ones mined from the data, Thurner and Klimek hope to be able to predict the health of individuals or of a population over time. On the clinical side, Longhurst has been advocating for a button in electronic medical-record software that would allow doctors to run automated searches for patients like theirs when no other sources of information are available.
With time, and with some crucial refinements, this kind of medicine may eventually become mainstream. Frankovich recalls a conversation with an older colleague. “She told me, ‘Research this decade benefits the next decade,’ ” Frankovich says. “That was how it was. But I feel like it doesn’t have to be that way anymore.”

For the full story, see:
VERONIQUE GREENWOOD. “Eureka; Dr. DATA; Can Statistical Analysis Tell Us What Clinical Trials Cannot?” The New York Times Magazine (Sun., OCT. 5, 2014): 16-17.
(Note: ellipses, and bracketed name, added.)
(Note: the online version of the story has the date OCT. 3, 2014, and has the title “Eureka; Can Big Data Tell Us What Clinical Trials Don’t?”)

“You Don’t Reach Serendip by Plotting a Course for It”

(p. 320) As John Barth wrote in The Last Voyage of Somebody the Sailor, “You don’t reach Serendip by plotting a course for it. You have to set out in good faith for elsewhere and lose your bearings serendipitously.”28 The challenge for educational institutions, government policy, research centers, funding agencies, and, by extension, all modern medicine, will be how to encourage scientists to lose their bearings creatively. What they discover may just save our lives!

Source:
Meyers, Morton A. Happy Accidents: Serendipity in Modern Medical Breakthroughs. New York: Arcade Publishing, 2007.
(Note: italics in original.)

Outsiders Persevere to Pursue Breakthroughs

(p. 315) Despite all the examples given, mainstream medical research stubbornly continues to assume that new drugs and other advances will follow exclusively from a predetermined research path. Many, in fact, will. Others, if history is any indication, will not. They will come not from a committee or a research team but from an individual, a maverick who views a problem with fresh eyes. Serendipity will strike and be seized upon by a well-trained scientist or clinician who also dares to rely upon intuition, imagination, and creativity. Unbound by traditional theory, willing to suspend the usual set of beliefs, unconstrained by the requirement to obtain approval or funding for his or her pursuits, this outsider will persevere and lead the way to a dazzling breakthrough. Eventually, once the breakthrough becomes part of accepted medical wisdom, the insiders will pretend that the outsider was one of them all along.

Source:
Meyers, Morton A. Happy Accidents: Serendipity in Modern Medical Breakthroughs. New York: Arcade Publishing, 2007.

Successful Discoverers “Follow the Evidence Wherever It Leads”

(p. 314) Why are particular people able to seize on such opportunities and say, “I’ve stumbled upon a solution. What’s the problem?” Typically, such people are not constrained by an overly focused or dogmatic mindset. In contrast, those with a firmly held set of preconceptions are less likely to be distracted by an unexpected or contradictory observation, and yet it is exactly such things that lead to the blessing of serendipitous discovery.
Serendipitous discoverers have certain traits in common. They have a passionate intensity. They insist on trying to see beyond their own and others’ expectations and resist any pressure that would close off investigation. Successful medical discoverers let nothing stand in their way. They break through, sidestep, or ignore any obstacle or objection to their chosen course, which is simply to follow the evidence wherever it leads. They have no patience with dogma of any kind.
The only things successful discoverers do not dismiss out of hand are contradictory–and perhaps serendipitously valuable–facts. They painstakingly examine every aspect of uncomfortable facts until they understand how they fit with other facts. Far from being cavalier about method, serendipitous discoverers subject their evidence and suppositions to the most rigorous methods they can find. They do not run from uncertainty, but see it as the raw material from which new scientific and medical certainties can be wrought.

Source:
Meyers, Morton A. Happy Accidents: Serendipity in Modern Medical Breakthroughs. New York: Arcade Publishing, 2007.

While Looking for Spotted Fever, He Found the Cause of Lyme Disease

(p. A25) Willy Burgdorfer, a medical entomologist who in 1982 identified the cause of what had been a mysterious affliction, Lyme disease, died on Monday [November 17, 2014] at a hospital in Hamilton, Mont. He was 89.
. . .
In the early 1980s, Dr. Burgdorfer was analyzing deer ticks from Long Island that were suspected to have caused spotted fever when he stumbled on something unexpected under his microscope: spirochetes, disease-causing bacteria shaped like corkscrews. They were located in only one section of the ticks, the so-called midguts. He had studied spirochetes in graduate school.
“Once my eyes focused on these long, snakelike organisms, I recognized what I had seen a million times before: spirochetes,” he said in a 2001 oral history for the National Institutes of Health, which include the National Institute of Allergy and Infectious Diseases.
He had not been working on Lyme disease, but he had spoken with the doctor who helped discover it, Dr. Allen Steere of Yale. After he saw the spirochetes in the Long Island ticks, he quickly realized that the bacteria might also be in the deer ticks believed to be playing a role in Lyme disease in Connecticut and elsewhere, including Long Island.

For the full obituary, see:
WILLIAM YARDLEY. “Willy Burgdorfer, Who Found Bacteria That Cause Lyme Disease, Is Dead at 89.” The New York Times (Thurs., NOV. 20, 2014): A25.
(Note: ellipsis, and bracketed date, added.)
(Note: the online version of the obituary has the date NOV. 19, 2014.)

“Peer Review Institutionalizes Dogmatism by Promoting Orthodoxy”

(p. 305) Peer review institutionalizes dogmatism by promoting orthodoxy. Reviewers prefer applications that mesh with their own perspective on how an issue should be conceptualized, and they favor individuals whom they know or whose reputations have already been established, making it harder for new people to break into the system.6 Indeed, the basic process of peer review demands conformity of thinking and disdains a maverick’s approach. “We can hardly expect a committee,” said the biologist and historian of science, Garrett Hardin, “to acquiesce in the dethronement of tradition. Only an individual can do that.”7 Young investigators get the message loud and clear: Do not challenge existing beliefs and practices.
So enmeshed in the conventional wisdoms of the day, so-called “peers” have again and again failed to appreciate major breakthroughs even when they were staring them in the face. This reality is evidenced by the fact that so many pioneering researchers were inappropriately scheduled to present their findings at undesirable times when few people were in the audience to hear about them.

Source:
Meyers, Morton A. Happy Accidents: Serendipity in Modern Medical Breakthroughs. New York: Arcade Publishing, 2007.

With Targeted Research, Scientists Not Allowed to Pursue Serendipitous Discoveries

(p. 303) When scientists were allowed to pursue whatever they found, serendipitous discovery flourished.
Today, targeted research is pretty much all there is. Yet, as Richard Feynman put it in his typical rough-hewn but insightful manner, giving more money “just increases the number of guys following the comet head.”2 Money doesn’t foster new ideas, ideas that drive science; it only fosters applications of old ideas, most often enabling improvements but not discoveries.

Source:
Meyers, Morton A. Happy Accidents: Serendipity in Modern Medical Breakthroughs. New York: Arcade Publishing, 2007.

Government Funding Rewards Conformity

(p. 302) Inherent in the system is a mindset of conformity: one will tend to submit only proposals that are likely to be approved, which is to say, those that conform to the beliefs of most members on the committee of experts. Because of the intense competition for limited money, investigators are reluctant to submit novel or maverick proposals. Needless to say, this environment stifles the spirit of innovation. Taking risks, pioneering new paths, thwarting conventional wisdom–the very things one associates with the wild-eyed, wild-haired scientists of the past–don’t much enter into the picture nowadays.

Source:
Meyers, Morton A. Happy Accidents: Serendipity in Modern Medical Breakthroughs. New York: Arcade Publishing, 2007.

Government Funding Not Conducive to Serendipity

(p. 301) Even in the early twentieth century, the climate was more conducive to serendipitous discovery. In the United States, for example, scientific research was funded by private foundations, notably the Rockefeller Institute for Medical Research in New York (established 1901) and the Rockefeller Foundation (1913). The Rockefeller Institute modeled itself on prestigious European organizations such as the Pasteur Institute in France and the Koch Institute in Germany, recruiting the world’s best scientists and providing them with comfortable stipends, well-equipped laboratories, and freedom from teaching obligations and university politics, so that they could devote their energies to research. The Rockefeller Foundation, which was the most expansive supporter of basic research, especially in biology, between the two world wars, relied on successful programs to seek promising scientists to identify and accelerate burgeoning fields of interest. In Britain, too, the Medical Research Council believed in “picking the man, not the project,” and nurturing successful results with progressive grants.
After World War II, everything about scientific research changed. The U.S. government–which previously had had little to do with funding research except for some agricultural projects–took on a major role. The National Institutes of Health (NIH) grew out of feeble beginnings in 1930 but became foremost among the granting agencies in the early 1940s at around the time they moved to Bethesda, Maryland. The government then established the National Science Foundation (NSF) in 1950 to promote progress in science and engineering. Research in the United States became centralized and therefore suffused with bureaucracy. The lone scientist working independently was now a rarity. Research came to be characterized by large teams drawing upon multiple scientific disciplines and using highly technical methods in an environment that promoted the not-very-creative phenomenon known as “groupthink.” Under this new regime, the competition (p. 302) among researchers for grant approvals fostered a kind of conformity with existing dogma. As the bureaucracy of granting agencies expanded, planning and justification became the order of the day, thwarting the climate in which imaginative thought and creative ideas flourish.

Source:
Meyers, Morton A. Happy Accidents: Serendipity in Modern Medical Breakthroughs. New York: Arcade Publishing, 2007.

Eisenhower Warned that “a Government Contract Becomes Virtually a Substitute for Intellectual Curiosity”

(p. 300) In his farewell address on January 17, 1961, President Dwight Eisenhower famously cautioned the nation about the influence of the “military-industrial complex,” coining a phrase that became part of the political vernacular. However, in the same speech, he presciently warned that scientific and academic research might become too dependent on, and thus shaped by, government grants. He foresaw a situation in which “a government contract becomes virtually a substitute for intellectual curiosity.”

Source:
Meyers, Morton A. Happy Accidents: Serendipity in Modern Medical Breakthroughs. New York: Arcade Publishing, 2007.

Loewi Proved a Slow Hunch after 17 Years

(p. 243) Loewi had long been interested in the problem of neurotransmission and believed that the agent was likely a chemical substance and not an electrical impulse, as previously thought, but he was unable to find a way to test the idea. It lay dormant in his mind for seventeen years. In a dream in 1921, on the night before Easter Sunday, he envisioned an experiment to prove this. Loewi awoke from the dream and, by his own account, “jotted down a few notes on a tiny slip of thin paper.” Upon awakening in the morning, he was terribly distressed: “I was unable to decipher the scrawl.”
The next night, at three o’clock, the idea returned. This time he got up, dressed, and started a laboratory experiment.

Source:
Meyers, Morton A. Happy Accidents: Serendipity in Modern Medical Breakthroughs. New York: Arcade Publishing, 2007.