Category: Methodology

Majerus Did Not Need a Randomized Trial to Know that Aspirin Prevents Heart Attacks

(p. A21) Philip W. Majerus, a biochemist who was credited as being the first to theorize that taking small doses of aspirin regularly can prevent heart attacks and strokes in vulnerable patients, died last Wednesday [June 8, 2016] at his home in St. Louis. . . .
. . .
Even before his findings were confirmed in a study by other researchers a decade later, Dr. Majerus was taking aspirin daily.
“I was already convinced that aspirin prevented heart attacks,” he recalled in the journal Advances in Biological Regulation in 2014. “I was unwilling to be randomized into a trial where I might end up with the placebo. I refused to participate.”
Dr. Majerus recommended that “all adults should take an aspirin daily unless they are among the few percent of the population that cannot tolerate the drug.” The cardiovascular benefit of aspirin was fully achieved by 50 to 75 milligrams daily, he said, and “there is no evidence that branded aspirin, which is much more expensive, is in any way superior to the generic version.”
Later studies found that for people in their 50s who are vulnerable to heart disease, taking daily doses of aspirin reduces the risk of heart disease.
. . .
Investigating how aspirin inhibited clotting, Dr. Majerus concluded that the medicine modified an enzyme that leads to the formation of a platelet-made molecule that constricts blood vessels and aggregates platelets. The pills’ effect lasts for the platelets’ life span, typically about two weeks.
“Phil Majerus, more than any other individual, has produced the most original body of work on biochemistry of platelets as it relates to thrombosis,” Prof. Joseph L. Goldstein, a Nobel laureate at the University of Texas Southwestern Medical Center in Dallas, said when the Bristol-Myers Squibb Award was announced.

For the full obituary, see:
SAM ROBERTS. “Dr. Philip Majerus, Who Recognized Heart Benefits of Aspirin, Is Dead at 79.” The New York Times (Weds., JUNE 15, 2016): A23.
(Note: ellipses, and bracketed date, added.)
(Note: the online version of the obituary has the date JUNE 14, 2016, and has the title “Dr. Philip Majerus, Who Discerned Aspirin’s Heart Benefits, Dies at 79.”)

Half of Important Psychology Articles Could Not Be Replicated

(p. A1) The past several years have been bruising ones for the credibility of the social sciences. A star social psychologist was caught fabricating data, leading to more than 50 retracted papers. A top journal published a study supporting the existence of ESP that was widely criticized. The journal Science pulled a political science paper on the effect of gay canvassers on voters’ behavior because of concerns about faked data.
Now, a painstaking yearslong effort to reproduce 100 studies published in three leading psychology journals has found that more than half of the findings did not hold up when retested. The analysis was done by research psychologists, many of whom volunteered their time to double-check what they considered important work. Their conclusions, reported Thursday [August 27, 2015] in the journal Science, have confirmed the worst fears of scientists who have long worried that the field needed a strong correction.
The vetted studies were considered part of the core knowledge by which scientists understand the dynamics of personality, relationships, learning and memory. Therapists and educators rely on such findings to help guide decisions, and the fact that so many of the studies were called into question could sow doubt in the scientific underpinnings of their work.

For the full story, see:
BENEDICT CAREY. “Psychology’s Fears Confirmed: Rechecked Studies Don’t Hold Up.” The New York Times (Fri., AUG. 28, 2015): A1 & A13.
(Note: bracketed date added.)
(Note: the online version of the story has the date AUG. 27, 2015 and has the title “Many Psychology Findings Not as Strong as Claimed, Study Says.”)

The Science article reporting the large number of psychology articles that proved unreplicable, is:
Open Science Collaboration. “Estimating the Reproducibility of Psychological Science.” Science 349, no. 6251 (Aug. 28, 2015): 943.

Many Empirical Research Results Are False

(p. B7) Research on 100 studies in psychology found in 2015 that more than 60% couldn’t be replicated. Similar results have been found in medicine and economics. Campbell Harvey, a professor at Duke University and president of the American Finance Association, estimates that at least half of all “discoveries” in investment research, and financial products based on them, are false.
. . .
Brian Nosek, a psychology professor at the University of Virginia and executive director of the Center for Open Science, a nonprofit seeking to improve research practices, has spent much of the last decade analyzing why so many studies don’t stand up over time.
Because researchers have an incentive to come up with results that are “positive and clean and novel,” he says, they often test a plethora of ideas, throwing out those that don’t appear to work and pursuing those that confirm their own hunches.
If the researchers test enough possibilities, they may find positive results by chance alone — and may fool themselves into believing that luck didn’t determine the outcomes.

For the full commentary, see:
JASON ZWEIG. “Chasing Hot Returns in ‘Smart-Beta’ Can Be Dumb.” The Wall Street Journal (Sat., Feb 13, 2016): B1 & B7.
(Note: ellipsis added.)
(Note: the online version of the commentary has the date Feb 12, 2016, and has the title “Chasing Hot Returns in ‘Smart-Beta’ Funds Can Be a Dumb Idea.”)

“Science Is Not a Body of Infallible Work, of Immutable Laws”

(p. 1) . . . , “Failure: Why Science Is So Successful” is a breath of contemplative fresh air. Stuart ­Fire­stein, a professor in the department of biological sciences at Columbia University, is best known for his work on ignorance, including inviting scientists to speak to his students about what they don’t know. In a tone reminiscent of Lewis Thomas’s “The Lives of a Cell,” the book is a collection of loosely interwoven meditations on failure and scientific method.
. . .
If we succeed by failing, then we should be freed from the monolithic road to academic tenure; science should be taught as an adventure in failure. With a delightful combination of feigned naïveté and keen eye for the messy ways that great discoveries occur, he goes so far as to suggest writing a grant proposal in which you promise to fail better. He knows this isn’t how the world works, but nevertheless argues that change will take place “when we cease, or at least reduce, our devotion to facts and collections of them, when we decide that science education is not a memorization marathon, when we — scientists and nonscientists — recognize that science is not a body of infallible work, of immutable laws of facts. . . . And that most of what there is to know is still unknown.”

For the full review, see:
ROBERT A. BURTON. “Error Messages.”The New York Times, SundayReview Section (Sun., Jan. 3, 2016): 8.
(Note: first two ellipses added; third ellipsis in original.)
(Note: the online version of the review has the date DEC. 29, 2015, and has the title “‘Black Box Thinking’ and ‘Failure: Why Science Is So Successful’.”)

The book under review, is:
Firestein, Stuart. Failure: Why Science Is So Successful. New York: Oxford University Press, 2016.

Serendipity May Be Source of 50% of Patents

(p. 1) A surprising number of the conveniences of modern life were invented when someone stumbled upon a discovery or capitalized on an accident: the microwave oven, safety glass, smoke detectors, artificial sweeteners, (p. 4) X-ray imaging. Many blockbuster drugs of the 20th century emerged because a lab worker picked up on the “wrong” information.
. . .
(p. 5) So how many big ideas emerge from spills, crashes, failed experiments and blind stabs? One survey of patent holders (the PatVal study of European inventors, published in 2005) found that an incredible 50 percent of patents resulted from what could be described as a serendipitous process. Thousands of survey respondents reported that their idea evolved when they were working on an unrelated project — and often when they weren’t even trying to invent anything. This is why we need to know far more about the habits that transform a mistake into a breakthrough.
. . .
A number of pioneering scholars have already begun this work, but they seem to be doing so in their own silos and without much cross-talk. In a 2005 paper (“Serendipitous Insights Involving Nonhuman Primates”), two experts from the Washington National Primate Research Center in Seattle cataloged the chance encounters that yielded new insights from creatures like the pigtail macaque. Meanwhile, the authors of a paper titled “On the Exploitation of Serendipity in Drug Discovery” puzzled over the reasons the 1950s and ’60s saw a bonanza of breakthroughs in psychiatric medication, and why that run of serendipity ended.

For the full commentary, see:
PAGAN KENNEDY. “How to Cultivate the Art of Serendipity.” The New York Times, SundayReview Section (Sun., JAN. 3, 2016): 1 & 4-5.
(Note: ellipses added.)
(Note: the online version of the commentary has the date JAN. 2, 2016, and has the title “Cultivating the Art of Serendipity.”)

Pagan’s commentary is based on her book:
Kennedy, Pagan. Inventology: How We Dream up Things That Change the World. New York: Houghton Mifflin Harcourt Publishing Co., 2016.

Scientific Insight Requires Hard Work More than Easy Epiphany

(p. A21) The myth of the finches obscures the qualities that were really responsible for Darwin’s success: the grit to formulate his theory and gather evidence for it; the creativity to seek signs of evolution in existing animals, rather than, as others did, in the fossil record; and the open-mindedness to drop his belief in creationism when the evidence against it piled up.
The mythical stories we tell about our heroes are always more romantic and often more palatable than the truth. But in science, at least, they are destructive, in that they promote false conceptions of the evolution of scientific thought.
Of the tale of Newton and the apple, the historian Richard S. Westfall wrote, “The story vulgarizes universal gravitation by treating it as a bright idea … A bright idea cannot shape a scientific tradition.” Science is just not that simple and it is not that easy.
. . .
Even if we are not scientists, every day we are challenged to make judgments and decisions about technical matters like vaccinations, financial investments, diet supplements and, of course, global warming. If our discourse on such topics is to be intelligent and productive, we need to dip below the surface and grapple with the complex underlying issues. The myths can seduce one into believing there is an easier path, one that doesn’t require such hard work.
But even beyond issues of science, there is a broader lesson to learn, . . . . We all run into difficult problems in life, and we will be happier and more successful if we appreciate that the answers often aren’t quick, or easy.

For the full commentary, see:
LEONARD MLODINOW. “It Is, in Fact, Rocket Science.” The Wall Street Journal (Sat., MAY 16, 2015): A21.
(Note: ellipsis internal to third quoted paragraph, in original; other ellipses, added.)
(Note: the online version of the commentary was updated on MAY 15, 2015.)

Mlodinow’s book, related to the commentary quoted above, is:
Mlodinow, Leonard. The Upright Thinkers: The Human Journey from Living in Trees to Understanding the Cosmos. New York: Pantheon Books, 2015.

Lives Lost Due to Peer Review Delays

(p. A25) In this age of instant information, medicine remains anchored in the practice of releasing new knowledge at a deliberate pace. It’s time for medical scientists to think differently about how quickly they alert the public to breakthrough findings.
Last week the National Institutes of Health announced that it had prematurely ended a large national study of how best to treat people with high blood pressure because of its exceptional results.
In this trial of more than 9,000 people age 50 and older with high blood pressure, an aggressive treatment strategy to keep systolic blood pressure below 120 was compared with a conventional one aimed at keeping it below 140. The subjects all had a high risk of heart attacks, stroke and heart failure. The N.I.H. concluded, six years into a planned eight-year study, that for these patients, pushing blood pressure down far below currently recommended levels was very beneficial.
. . .

The new information may justify a more vigorous strategy for treating blood pressure, but for now doctors and patients have been left with incomplete results, some headlines and considerable uncertainty about whether to modify current treatments.
Medicine needs to change its approach to releasing new, important information. Throughout science we are seeing more rapid modes of communication. The traditional approach was not to publish until everything was finalized and ready to be chiseled in stone. But these sorts of delays are unnecessary with the Internet. Moreover, although all the trial data has yet to be tabulated, an analysis was considered sufficiently definitive to lead independent experts to stop the multimillion-dollar study.
We believe that when there is such strong evidence for a major public health condition, there should be rapid release of the information that led to the decision to stop the trial. This approach could easily be accomplished by placing the data on the N.I.H. website or publishing the data on such platforms as bioRxiv.org, which enables fast, open review by the medical community.
. . .
Kudos to the scientists who conducted such a large, complex and important study with what will be likely to have lifesaving consequences for a condition that can be treated easily in most patients. Now the medical community needs to adopt a new approach in situations like this one to disseminate lifesaving results in a timely, comprehensive and transparent way. Lives depend on it.

For the full commentary, see:
ERIC J. TOPOL and HARLAN M. KRUMHOLZ. “Don’t Sit on Medical Breakthroughs.” The New York Times (Fri., SEPT. 17, 2015): A25.
(Note: ellipses added.)
(Note: the online version of the commentary has the date SEPT. 17, 2015, and the title “Don’t Delay News of Medical Breakthroughs.”)

Those Who Use “Consensus” Argument on Global Warming, Should Endorse Genetically Modified Food

(p. B3) NAIROBI, Kenya — Mohammed Rahman doesn’t know it yet, but his small farm in central Bangladesh is globally significant. Mr. Rahman, a smallholder farmer in Krishnapur, about 60 miles northwest of the capital, Dhaka, grows eggplant on his meager acre of waterlogged land.
As we squatted in the muddy field, examining the lush green foliage and shiny purple fruits, he explained how, for the first time this season, he had been able to stop using pesticides. This was thanks to a new pest-resistant variety of eggplant supplied by the government-run Bangladesh Agricultural Research Institute.
Despite a recent hailstorm, the weather had been kind, and the new crop flourished. Productivity nearly doubled. Mr. Rahman had already harvested the small plot 10 times, he said, and sold the brinjal (eggplant’s name in the region) labeled “insecticide free” at a small premium in the local market. Now, with increased profits, he looked forward to being able to lift his family further out of poverty. I could see why this was so urgent: Half a dozen shirtless kids gathered around, clamoring for attention. They all looked stunted by malnutrition.
. . .
I, . . . , was once in [the] . . . activist camp. A lifelong environmentalist, I opposed genetically modified foods in the past. Fifteen years ago, I even participated in vandalizing field trials in Britain. Then I changed my mind.
After writing two books on the science of climate change, I decided I could no longer continue taking a pro-science position on global warming and an anti-science position on G.M.O.s.
There is an equivalent level of scientific consensus on both issues, I realized, that climate change is real and genetically modified foods are safe. I could not defend the expert consensus on one issue while opposing it on the other.

For the full commentary, see:
MARK LYNAS. “How I Got Converted to G.M.O. Food.” The New York Times, SundayReview Section (Sun., APRIL 26, 2015): 5.
(Note: ellipses, and bracketed word, added.)
(Note: the online version of the commentary has the date APRIL 24, 2015.)

“Strong-Willed Scientists Overstated the Significance of Their Studies”

The New York Times seems open to the idea that strong-willed scientists might overstate their results in science food studies. I wonder if The New York Times would be open to the same possibility in science climate studies?

(p. A19) For two generations, Americans ate fewer eggs and other animal products because policy makers told them that fat and cholesterol were bad for their health. Now both dogmas have been debunked in quick succession.
. . .
Epidemiological data can be used to suggest hypotheses but not to prove them.
Instead of accepting that this evidence was inadequate to give sound advice, strong-willed scientists overstated the significance of their studies.
Much of the epidemiological data underpinning the government’s dietary advice comes from studies run by Harvard’s school of public health. In 2011, directors of the National Institute of Statistical Sciences analyzed many of Harvard’s most important findings and found that they could not be reproduced in clinical trials.
It’s no surprise that longstanding nutritional guidelines are now being challenged.
In 2013, government advice to reduce salt intake (which remains in the current report) was contradicted by an authoritative Institute of Medicine study. And several recent meta-analyses have cast serious doubt on whether saturated fats are linked to heart disease, as the dietary guidelines continue to assert.
Uncertain science should no longer guide our nutrition policy. Indeed, cutting fat and cholesterol, as Americans have conscientiously done, may have even worsened our health.

For the full commentary, see:
NINA TEICHOLZ. “The Government’s Bad Diet Advice.” The New York Times (Sat., FEB. 21, 2015): A19.
(Note: ellipsis added.)
(Note: the online version of the commentary has the date FEB. 20, 2015.)

Experts Are Paid “to Sound Cocksure” Even When They Do Not Know

(p. B1) I think Philip Tetlock’s “Superforecasting: The Art and Science of Prediction,” co-written with the journalist Dan Gardner, is the most important book on decision making since Daniel Kahneman’s “Thinking, Fast and Slow.” (I helped write and edit the Kahneman book but receive no royalties from it.) Prof. Kahneman agrees. “It’s a manual to systematic thinking in the real world,” he told me. “This book shows that under the right conditions regular people are capable of improving their judgment enough to beat the professionals at their own game.”
The book is so powerful because Prof. Tetlock, a psychologist and professor of management at the University of Pennsylvania’s Wharton School, has a remarkable trove of data. He has just concluded the first stage of what he calls the Good Judgment Project, which pitted some 20,000 amateur forecasters against some of the most knowledgeable experts in the world.
The amateurs won–hands down.
. . .
(p. B7) The most careful, curious, open-minded, persistent and self-critical–as measured by a battery of psychological tests–did the best.
. . .
Most experts–like most people–“are too quick to make up their minds and too slow to change them,” he says. And experts are paid not just to be right, but to sound right: cocksure even when the evidence is sparse or ambiguous.

For the full review, see:
JASON ZWEIG. “The Trick to Making Better Forecasts.” The Wall Street Journal (Sat., Sept. 26, 2015): B1 & B7.
(Note: ellipses added.)
(Note: the online version of the review has the date Sept. 25, 2015.)

The book under review, is:
Tetlock, Philip E., and Dan Gardner. Superforecasting: The Art and Science of Prediction. New York: Crown, 2015.

“Stunned” Geophysicists Are Headed “Back to the Drawing Board”

(p. A3) Bringing the blur of a distant world into sharp focus, NASA unveiled its first intimate images of Pluto on Wednesday [July 15, 2015], revealing with startling clarity an eerie realm where frozen water rises in mountains up to 11,000 feet high.
. . .
At a briefing held Wednesday [July 15, 2015] at the Johns Hopkins Applied Physics Laboratory in Laurel, Md., mission scientists said they were stunned by what the images reveal.
“It is going to send a lot of geophysicists back to the drawing board,” said Alan Stern, the New Horizons project’s principal investigator, from the Southwest Research Institute in Boulder, Colo.

For the full story, see:
ROBERT LEE HOTZ. “Across 3 Billion Miles of Space, NASA Probe Sends Close-Ups of Pluto’s Icy Mountains.” The Wall Street Journal (Thurs., JULY 16, 2015): A3.
(Note: ellipsis, and bracketed dates, added.)
(Note: the online version of the article has the date JULY 15, 2015, has the title “NASA Releases Close-Up Pictures of Pluto and Its Largest Moon, Charon,” and has some different wording than the print version. The quote above follows the online version.)