of which Huge Mediterranean Diet Study Was Flawed. although Was the idea Wrong?

A highly publicized trial in Spain found of which the Mediterranean diet protects against heart disease. currently the original work has been retracted in addition to re-analyzed, with the same result.

An olive farm in Tuscany. Participants in a study of the Mediterranean diet were not always assigned at random to test various diets, the investigators conceded.CreditGiulio Piscitelli for The brand new York Times

The study was a landmark, one of the few attempts to rigorously evaluate a particular diet. in addition to the results were striking: A Mediterranean diet, with abundant vegetables in addition to fruit, can slash the risk of heart attacks in addition to strokes.

although currently of which trial, published from the brand new England Journal of Medicine in 2013, has come under fire. The authors retracted their original paper on Wednesday in addition to published an unusual “re-analysis” of their data from the same journal.

Despite serious problems from the way the study was conducted, their conclusions are the same: A Mediterranean diet can cut the risk of heart attacks in addition to strokes by about 30 percent in those at high risk.

Not everyone can be convinced. “Nothing they have done in This kind of re-analyzed paper makes me more confident,” said Dr. Barnett Kramer, director of the division of cancer prevention at the National Cancer Institute.

For decades, researchers have noted of which people living in some Mediterranean countries have lower rates of heart disease in addition to cancer. Scientists have long suspected of which the regional diet — rich in fruits, vegetables, nuts in addition to olive oil, with moderate levels of fat — played a protective role.

although the idea has been hard to prove. the idea can be very difficult to test any diet in a clinical trial. Participants may be reluctant to stick to the prescribed meal plan, for instance, in addition to the idea can be difficult to monitor them over months or years.

The original study was conducted in Spain by Dr. Miguel A. Martínez-González of the University of Navarra in addition to his colleagues. The trial enrolled 7,447 participants aged 55 to 80 who were assigned one of three diets: a Mediterranean diet with at least four tablespoons a day of extra virgin olive oil; the same diet with an ounce of mixed nuts; or a traditional low-fat diet.

The participants were followed for a median of nearly several years. Dr. Martínez-González in addition to his colleagues reported of which there were fewer cardiovascular events from the groups consuming olive oil in addition to nuts.

although last year Dr. Martínez-González found his study on a list of clinical trials whose data seemed suspect, compiled by Dr. John Carlisle of Torbay Hospital in England.

“of which was the first hint of which there could have been some imperfection,” Dr. Martínez-González said in an interview.

A statistician at the brand new England Journal of Medicine suggested the researchers look at the methods at each center of which recruited participants.

The idea of a randomized trial can be to assign treatments — in This kind of case, diets — to participants with the statistical equivalent of a coin toss. of which way, the groups being compared should be equivalent, with no group healthier or sicker, or older or younger, than another on average.

If subjects are not assigned at random, the investigators cannot be sure of which the effects they see result through the treatment. in addition to attempts to correct statistically after the fact are fraught with difficulty.

On re-evaluating their data, the scientists running the Mediterranean diet study soon found what Dr. Martínez-González said were “little problems affecting 10 percent of participants.”

Some investigators would likely assign one person in a household — the wife, for example — to one arm of the study — say, to the group consuming olive oil. Then they would likely ask different members of the household to share of which diet, including them as though they had been randomly assigned to the idea.

“We realized we had never reported of which,” Dr. Martínez-González said.

Dr. Miguel A. Martínez-GonzálezCreditvia Wikimedia Commons

An omission like of which erodes the randomized nature of the trial. Family members are likely to share more than just a diet: If a husband in addition to wife both dodge heart disease, the idea’s difficult to say of which their diet can be the only reason.

In their re-analysis, the investigators statistically adjusted data on 390 people who happened to be household members although whose diets were not randomly assigned.

Then the investigators discovered another problem.

A researcher at one of the 11 clinical centers from the trial worked in little villages. Participants there complained of which some neighbors were receiving free olive oil, while they got only nuts or inexpensive gifts.

So the investigator decided to give everyone in each village the same diet. He never told the leaders of the study what he had done.

“He did not think the idea was important,” Dr. Martínez-González said.

although the decision meant of which participants were not truly randomized in addition to forced Dr. Martínez-González in addition to his colleagues to make another statistical adjustment to data on 652 people from the trial.

The investigators spent a year working on the re-analysis in collaboration with Dr. Miguel Hernan of the Harvard T.H. Chan School of Public Health.

from the end, they concluded of which the original findings were still accurate.

“You cannot imagine what the idea has been like,” Dr. Martínez-González said, adding of which he in addition to his team worked through vacations in addition to weekends — in addition to swallowed considerable professional embarrassment.

Randomized trials are difficult, different experts agreed, in addition to randomized diet studies so perilous they are seldom attempted.

“These people were naïve,” said Donald Berry, a statistician at MD Anderson Cancer Center in Houston. “They were sloppy in addition to didn’t know they were being sloppy.”

Dr. Berry said he wants to believe the results. He loves nuts in addition to has taken to cooking with extra virgin olive oil.

although he remains unconvinced, because the re-analysis did not solve the study’s problems, he said.

Dr. Bradley Efron, a statistics professor at Stanford University, also was skeptical. The revamped results “wouldn’t convince me to be on a Mediterranean diet,” he said.

although Dr. Steven Nissen, a cardiologist at the Cleveland Clinic, can be persuaded in addition to plans to continue advising patients to go on the Mediterranean diet.

When the initial paper was published, he said, “I was thrilled to see what seemed to be an impeccable trial.”

Although the idea was “sobering” to learn of the errors, “I was reassured of which the conclusions are correct,” he said.

Dr. Martínez-González shares the sentiment. “After all This kind of long work, I am more convinced than ever” by the study’s data.

“Seldom carries a trial undergone more scrutiny,” he added.

A type of This kind of article appears in print on , on Page A23 of the brand new York edition with the headline: Mediterranean-Diet Study can be Retracted, Then Reissued With Same Findings. Order Reprints | Today’s Paper | Subscribe