Posts about medical studies

Nearly 1 million Children Potentially Misdiagnosed with ADHD in the USA

Nearly 1 million children in the United States are potentially misdiagnosed with attention deficit hyperactivity disorder simply because they are the youngest – and most immature – in their kindergarten class, according to new research by , Todd Elder, a Michigan State University economist.

These children are significantly more likely than their older classmates to be prescribed behavior-modifying stimulants such as Ritalin, said Todd Elder, whose study will appear in a forthcoming issue of the Journal of Health Economics (closed science, unfortunately). Michigan State should stop funding closed journals with free content – other schools have decided to put science first, before supporting a few outdated business models of select journals.

Such inappropriate treatment is particularly worrisome because of the unknown impacts of long-term stimulant use on children’s health, Elder said. It also wastes an estimated $320 million-$500 million a year on unnecessary medication – some $80 million-$90 million of it paid by Medicaid, he said.

ADHD is the most commonly diagnosed behavioral disorder for kids in the United States, with at least 4.5 million diagnoses among children under age 18, according to the Centers for Disease Control and Prevention.

The youngest kindergartners were 60 percent more likely to be diagnosed with ADHD than the oldest children in the same grade. Similarly, when that group of classmates reached the fifth and eighth grades, the youngest were more than twice as likely to be prescribed stimulants.

Overall, the study found that about 20 percent – or 900,000 – of the 4.5 million children currently identified as having ADHD likely have been misdiagnosed.

Related: Lifestyle Drugs and RiskLong Term ADHD Drug Benefits QuestionedMerck and Elsevier Publish Phony Peer-Review Journal

Statistical Errors in Medical Studies

I have written about statistics, and various traps people often fall into when examining data before (Statistics Insights for Scientists and Engineers, Data Can’t Lie – But People Can be Fooled, Correlation is Not Causation, Simpson’s Paradox). And also have posted about reasons for systemic reasons for medical studies presenting misleading results (Why Most Published Research Findings Are False, How to Deal with False Research Findings, Medical Study Integrity (or Lack Thereof), Surprising New Diabetes Data). This post collects some discussion on the topic from several blogs and studies.

HIV Vaccines, p values, and Proof by David Rind

if vaccine were no better than placebo we would expect to see a difference as large or larger than the one seen in this trial only 4 in 100 times. This is distinctly different from saying that there is a 96% chance that this result is correct, which is how many people wrongly interpret such a p value.

So, the modestly positive result found in the trial must be weighed against our prior belief that such a vaccine would fail. Had the vaccine been dramatically protective, giving us much stronger evidence of efficacy, our prior doubts would be more likely to give way in the face of high quality evidence of benefit.

While the actual analysis the investigators decided to make primary would be completely appropriate had it been specified up front, it now suffers under the concern of showing marginal significance after three bites at the statistical apple; these three bites have to adversely affect our belief in the importance of that p value. And, it’s not so obvious why they would have reported this result rather than excluding those 7 patients from the per protocol analysis and making that the primary analysis; there might have been yet a fourth analysis that could have been reported had it shown that all important p value below 0.05.

How to Avoid Commonly Encountered Limitations of Published Clinical Trials by Sanjay Kaul, MD and and George A. Diamond, MD

Trials often employ composite end points that, although they enable assessment of nonfatal events and improve trial efficiency and statistical precision, entail a number of shortcomings that can potentially undermine the scientific validity of the conclusions drawn from these trials. Finally, clinical trials often employ extensive subgroup analysis. However, lack of attention to proper methods can lead to chance findings that might misinform research and result in suboptimal practice.

Why Most Published Research Findings Are False by John P. A. Ioannidis
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Engineer Tried to Save His Sister and Invented a Breakthrough Medical Device

Here is another remarkable example of the great benefit engineers provide society.

How a software engineer tried to save his sister and invented a breakthrough medical device

I wanted to help my sister as much as I could. I went to Medline, where there are hundreds of thousands of documents describing clinical studies, to see what I could find.

There are billions of dollars spent every year on clinical studies. I was surprised to discover that there were sometimes clinical studies of treatments for which there were no clinical applications. The trials would show successful results but no clinical applications.

I found a 1987 Italian funded set of clinical studies that showed successful treatment of tumors by the application of chemotherapy directly into the tumors. But I could find nothing since then.

It took us two years to do the engineering. And it has taken the FDA seven years and two months to approve the product for sale. We were able to shorten the FDA process a little by saying that it was similar to other devices that had already been approved.

Great stuff.

Related: Cardiac Cath Lab: Innovation on SiteSurgeon-engineer advances high-tech healingHome Engineering: Dialysis machineStoryCorps: Passion for Mechanical EngineeringEngineers Should Follow Their Hearts

Scientific Illiteracy Leaves Many at Risk in Making Health Care Judgements

Scientific literacy is important for many reasons and that importance has increased greatly over the last century. Medical research is often difficult to interpret. Often various studies seem to contradict each other. Often the conclusions that are drawn are far too broad (especially as the research conclusions are passed on and people hear of them overly simplified ways).

Many health care options are not obviously all good, or all bad, but instead a mix of benefits and risks, both of which include interactions with the individuals makeup. So we often see contradictory (and seemingly contradictory) advice. Without a level of scientific literacy it is very difficult for people to know how to react to medical advice.

We have numerous posts on the scientific inquiry process showing that acquiring scientific knowledge is complex and can be quite confusing in many instances. While understanding things are often less clear cut than they are presented it is still true that most often strategies for healthy living have far better practices that will provide far better results than alternatives.

The scientific illiteracy that has some think because their are risks no matter what is done that means there is no evidence some alternatives are far superior is very dangerous. As you can see in action now with those that risk their and others lives and health by doing things like not vaccinating their children, or driving when drunk, or driving when talking on a cell phone.

Without a scientifically literate society even completely obvious measures like not using antibiotics on viral infections are ignored.

Related: Long Term ADHD Drug Benefits QuestionedHow Prozac Sent Science Inquiry Off TrackLifestyle Drugs and RiskCorrelation is Not Causation: “Fat is Catching” Theory Exposed
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CDC: Reduce Salt in Your Diet

USA Center for Disease Control: Application of Lower Sodium Intake Recommendations for Adults, 1999-2006 study

In 2005-2006, an estimated 29% of U.S. adults had hypertension (i.e., high blood pressure), and another 28% had prehypertension. The estimated average intake of sodium for those in the United States over 2 years old was 3,436 mg/day while the U.S. Department of Health and Human Services and U.S. Department of Agriculture recommended adults should consume no more than 2,300 mg/day of sodium (equal to approximately 1 tsp of salt), but those in specific groups (i.e., all persons with hypertension, all middle-aged and older adults, and all blacks) should consume no more than 1,500 mg/day of sodium (69% of U.S. adults should consume no more than !,500 mg/day). There is substantial evidence linking greater sodium intake to higher blood pressure.

Sodium reduction is recommended for persons with hypertension and as a first line of intervention for persons with prehypertension. Public health actions to reduce sodium intake likely will include reducing the sodium content of processed foods; encouraging consumption of more low-sodium foods, such as fruits and vegetables; and providing more relevant information about sodium in food labeling.

The current daily percentage value for sodium in the nutrition facts panel of packaged foods is based on a previous federal guideline of 2,400 mg/day and is likely to mislead the majority of consumers, for whom the 1,500 mg/day limit is applicable.

Related: posts on healthy living and medical researchWhy ‘Licking Your Wounds’ WorksEat food. Not too much. Mostly plants.Active Amish Avoid ObesityTuberculosis Risk

Medical Study Integrity (or Lack Thereof)

Merck wrote drug studies for doctors

The drug maker Merck drafted dozens of research studies for a best-selling drug, then lined up prestigious doctors to put their names on the reports before publication, according to an article to be published Wednesday in a leading medical journal.

The article, based on documents unearthed in lawsuits over the pain drug Vioxx, provides a rare, detailed look in the industry practice of ghostwriting medical research studies that are then published in academic journals.

“It almost calls into question all legitimate research that’s been conducted by the pharmaceutical industry with the academic physician,” said Ross, whose article, written with colleagues, was published Wednesday in JAMA, The Journal of the American Medical Association, and posted Tuesday on the journal’s Web site.

Merck acknowledged Tuesday that it sometimes hired outside medical writers to draft research reports before handing them over to the doctors whose names eventually appear on the publication. But the company disputed the article’s conclusion that the authors do little of the actual research or analysis.

It is sad that the integrity of journals and scientists is so weak that they leave them open to such charges. The significant presence of the corrupting influence of too much money leaves doubt in my mind that the best science is the goal. Which is very sad. In, Funding Medical Research, I discussed my concern that universities are acting more like profit motivated organizations than science motivated organizations. I am in favor of profit motivated organization (those getting the micro-financing in this link, for example) but those organization should not be trusted to provide honest and balanced opinions they should be expected to provide biased opinions.

If universities (and scientists branding themselves as … at X university) want to be seen as honest brokers of science they can’t behave as though raising money, getting patents… are their main objectives. Many want to be able to get the money and retain the sense of an organization focused on the pursuit of science above all else. Sorry, you can’t have it both ways. You can, and probably should, try stake out some ground in the middle. And for me right now, partially because they fail to acknowledge the extent to which money seems to drive decisions I don’t believe they are trying to be open and honest, instead I get the impression they are leaning more toward trying to market and sell.
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Placebo Effect

Don’t laugh, sugar pills are the future

In fact the new study added nothing (and it was ridiculously badly reported): we already knew that antidepressants perform only marginally better than placebo, and the National Institute for Health and Clinical Excellence (Nice) guidelines has actively advised against using them in milder depression since 2004. But the more interesting questions are around placebo.

Another study from 2002 looked at 75 trials of antidepressants over the past 20 years, but looked only at the response in the placebo arms of the trials, and found that the response to placebo has increased significantly in recent years (as has the response to medication): perhaps our expectations of those drugs have increased, or perhaps, conversely to our earlier example, the trial designs have become systematically more flattering. I’m giving you tenuous data, on an interesting area, because I know you’re adult enough to cope with ambiguity.

Related: Placebo Response in Studies of Major DepressionAn Exploration of Neurotic Patients’ Responses to Placebo When Its Inert Content Is DisclosedDiscussing Medical Study ResultsWhy Most Published Research Findings Are False

Funding Medical Research

Cheap, ‘safe’ drug kills most cancers

It sounds almost too good to be true: a cheap and simple drug that kills almost all cancers by switching off their “immortality”. The drug, dichloroacetate (DCA), has already been used for years to treat rare metabolic disorders and so is known to be relatively safe. It also has no patent, meaning it could be manufactured for a fraction of the cost of newly developed drugs.

Evangelos Michelakis of the University of Alberta in Edmonton, Canada, and his colleagues tested DCA on human cells cultured outside the body and found that it killed lung, breast and brain cancer cells, but not healthy cells. Tumours in rats deliberately infected with human cancer also shrank drastically when they were fed DCA-laced water for several weeks.

DCA attacks a unique feature of cancer cells: the fact that they make their energy throughout the main body of the cell, rather than in distinct organelles called mitochondria. This process, called glycolysis, is inefficient and uses up vast amounts of sugar.

Until now it had been assumed that cancer cells used glycolysis because their mitochondria were irreparably damaged. However, Michelakis’s experiments prove this is not the case, because DCA reawakened the mitochondria in cancer cells. The cells then withered and died

The University of Alberta is raising funds to further the research. Some look at this and indite a funding system that does not support research for human health unless there is profit to be made. Much of the blame seems to go to profit focused drug companies. I can see room for some criticism. But really I think the criticism is misplaced.

The organizations for which curing cancer is the partial aim (rather than making money) say government (partial aim or public health…), public universities (partial aim of science research or medical research…), foundations, cancer societies, private universities… should fund such efforts, if they have merit. Universities have huge research budgets. Unfortunately many see profit as their objective and research as the means to the objective (based on their actions not their claims). These entities with supposedly noble purposes are the entities I blame most, not profit focused companies (though yes, if they claim an aim of health care they I would blame them too).

Now I don’t know what category this particular research falls into. Extremely promising or a decent risk that might work just like hundreds or thousands of other possibilities. But lets look at several possibilities. Some others thoughts on where it falls: Dichloroacetate to enter clinical trials in cancer patients, from a previous post here – Not a Cancer Cure Yet, The dichloroacetate (DCA) cancer kerfuffle, CBC’s ‘The Current’ on dichloroacetate (DCA), Dichloroacetate (DCA) Phase II Trial To Begin (“Like hundreds (if not, thousands) of compounds being tested to treat cancer, DCA was shown by Michelakis’ group earlier this year to slow the growth of human lung tumors in a preclinical rodent model.”).
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Surprising New Diabetes Data

Surprising New Diabetes Data

But these measures are only surrogates for disease. And in many cases, the connection between “better” numbers and better health is tenuous. In the case of cholesterol, many people won’t see a health benefit from lower numbers.

Now comes yet another sobering reminder that lowering a surrogate marker doesn’t necessarily bring better health. On Feb. 6, the National Institutes of Health announced it was halting a key trial for diabetes. Researchers had hoped the trial, dubbed ACCORD (Action to Control Cardiovascular Risk in Diabetes), would show that more aggressive lowering of blood sugar would significantly reduce deaths. Instead, the opposite happened. More people in the intensive treatment group died than in the group getting standard care. “A thorough review of the data shows that the medical treatment strategy of intensively reducing blood sugar below current clinical guidelines causes harm in these…patients,” says Dr. Elizabeth Nabel, director of the National Heart, Lung & Blood Institute.

Scientific study often results in less than clear conclusions, especially in complex systems. There is great difficulty understanding what is actually going on, what interactions are present, what factors are significant, etc.. One of the great problems with the low level of scientific literacy in the USA is so many people think science is about simple absolute truth.

Scientific inquiry, especially related to health care, must attempt to gain insights from confusing signals. To gain scientific literacy one must understand basics concepts, like data is a proxy for what you aim to understand. To understand yourself you need to accept that science is not math. For a long time we are going to have to do our best to build up our understanding of human health (and other complex systems) as best we can. We need to be able to sort out what are solid conclusion, what are guesses, what seem like reasonable explanation and what level of confidence we can have in statements.

It is not enough to learn facts we need to be able to think scientifically and comprehend the subtleties surrounding the advances in scientific understanding. Some criticize newspapers and popular science for providing too simplistic a view of new scientific knowledge. While this can be a problem I really see the problem much more serious if people read obviously overly simplistic articles and don’t understand that it is just scratching the surface. The reader needs to take responsibility too. I enjoy many great articles that gloss over many of the details but provide a quick view of intriguing new breakthroughs.

Related: New Questions on Treating CholesterolEvolution is Fundamental to ScienceContradictory Medical StudiesThe Study of Bee Colony Collapses ContinuesAntibiotics Too Often Prescribed for Sinus Woes