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Our future, our universe, and other weighty topics

Friday, June 9, 2017

Biomedical Blunders Blow Billions

In the new book Rigor Mortis: How Sloppy Science Creates Worthless Cures, Crushes Hopes, and Wastes Billions by Richard Harris, we are told this: “Misleading animal studies have led to billions of dollars worth of wasted effort and dead ends in the search for drugs.” There is a rather acidic visual on the front cover of the Rigor Mortis book. We see a toe tag tied around the letter “I” in the title, like the toe tag they tie around the toes of corpses. In the “Name” slot of the toe tag, we see: “Biomedical Research.”

That visual is an exaggeration, since biomedical research isn't dead. But judging from the book, there are serious problems in the field. It seems that a very large fraction of research studies cannot be replicated. The problem was highlighted in a widely cited 2005 paper by John Ioannidis entitled, “Why Most Published Research Studies Are False.” A scientist named C. Glenn Begley and his colleagues tried to reproduce 53 published studies called “ground-breaking.” He asked the scientists who wrote the papers to help, by providing the exact materials to publish the results. Begley and his colleagues were only able to reproduce 6 of the 53 experiments.

In 2011 Bayer reported similar results. They tried to reproduce 67 medical studies, and were only able to reproduce them 25 percent of the time. On page 14 of the book by Harris, we are told that one expert estimates that 28 billion dollars a year is spent on untrustworthy papers.

Part of the problem is a culture that provides high rewards for splashy results that can be called “ground-breaking,” but which makes it rather hard for a biologist to get a paper published if the paper reports a failure to replicate a previous study. Another part of the problem is insufficient attention to methodology and precise mathematics. One expert quoted on page 172 says that in the current culture of biomedical research, it “pays to be first” but “it doesn't necessarily pay to be right.” The expert laments, “It actually pays to be sloppy and just cut corners and get there first,” noting that this is “really wrong.”

On page 96 we learn about a problem with misidentified cell lines, in which experiments are done assuming some series of cells are from one type of organism when they are actually from some other type of organism. We read:

A 2007 study estimated that between 18 and 36 percent of all cell experiments use misidentified cell lines. That adds up to tens of thousands of studies, costing billions of dollars....Sometimes, even the species isn't correct. Nelson-Rees found a “mongoose” cell line was actually human and determined that two “hamster” cell lines were from marmosets and humans, respectively. “Have the Marx Brothers taken over the cell-culture labs?” Roland Nardone asked in a 2008 paper bemoaning this state of affairs.

On page 203 of the Harris book, an expert laments that “we haven't trained a lot of our biologists to think mathematically or to understand or analyze data.” On the same page we are told that there are no standards in whole genome sequencing, that there are no standards in searching for mutations in genomes, and that in searching for mutations in genomes, “Nobody does it the same way.”

A Pro Publica article is entitled, “When Evidence Says No, But Doctors Say Yes.” Apparently there is a problem of some doctors recommending procedures that aren't backed up by evidence. Below is a quote from the article:

In a 2013 study, a dozen doctors from around the country examined all 363 articles published in The New England Journal of Medicine over a decade — 2001 through 2010 — that tested a current clinical practice, from the use of antibiotics to treat people with persistent Lyme disease symptoms (didn’t help) to the use of specialized sponges for preventing infections in patients having colorectal surgery (caused more infections). Their results, published in the Mayo Clinic Proceedings, found 146 studies that proved or strongly suggested that a current standard practice either had no benefit at all or was inferior to the practice it replaced; 138 articles supported the efficacy of an existing practice, and the remaining 79 were deemed inconclusive.

Another huge problem in contemporary medical practice involves doctors who invest in fantastically expensive equipment, and who then give advice that may be biased by their desire to pay off the cost of such a machine (or profit from its use).

unnecessary medical care

It seems that there is a huge amount of unnecessary medical treatment being done. A New Yorker article by a doctor states the following:

In just a single year, the researchers reported, twenty-five to forty-two per cent of Medicare patients received at least one of the twenty-six useless tests and treatments....The Institute of Medicine issued a report stating that waste accounted for thirty per cent of health-care spending, or some seven hundred and fifty billion dollars a year, which was more than our nation’s entire budget for K-12 education....Millions of people are receiving drugs that aren’t helping them, operations that aren’t going to make them better, and scans and tests that do nothing beneficial for them, and often cause harm.

If you are asked to take some expensive test or undergo some expensive medical procedure, the following are good questions to ask your doctor:

(1) Is the course of treatment or testing you are recommending considered a standard practice or "best practice" for patients with my set of circumstances? 
(2) If you were teaching a room full of medical students, would you recommend this exact treatment or testing for someone with my set of circumstances?

Look for a firm, confident answer of "Yes," rather than a weaker answer such as "Doctors often do this."

During earlier times, people had complete faith in words spoken by anyone wearing the black outfit of the priest. Today we have somehow been socially conditioned to regard anyone with a white coat as a totally reliable source of information. Perhaps both forms of “color confidence” involved too much uncritical trust.

Postscript:  An article in the Guardian states the following:

More than 70% of the researchers (pdf), who took part in a recent study published in Nature have tried and failed to replicate another scientist’s experiment. Another study found that at least 50% of life science research cannot be replicated. 

A Nature article states this: "Although 52% of those surveyed agree that there is a significant ‘crisis’ of reproducibility, less than 31% think that failure to reproduce published results means that the result is probably wrong, and most say that they still trust the published literature." This smells like scientists having too much overconfident faith in their fellow scientists.