Archive for Clinical Trials

Taxpayers Fund Scientology Research on Gulf War Veterans

Church_of_Scientology, Fountain Avenue, Los Angeles

The “Hubbard protocol” is Scientology’s religion-based, pseudoscientific “detoxification” treatment used in its Narconon program to treat drug addiction. It was dreamed up by a science fiction writer with no medical training. Now it is being studied as a treatment for veterans suffering from Gulf War illness. Our limited public money for research is being wasted on a study with no scientific merit. Whether or not you consider this a church/state conflict, the study is clearly ill-advised.

The study: $600K worth of sweat

A description of the study is available online in the government’s clinical trials registry. The DOD funded this study to the tune of $633,677. The subjects are veterans with Gulf War illness characterized by persistent memory and concentration problems, headaches, fatigue, and muscle and joint pain. The illness has not been well defined, and its cause has not been determined; but the researchers are working on the assumption that toxins are the cause and that the treatment will relieve symptoms by removing toxins from the body.

The control group will get only “usual care.” The experimental group will get:

A four to six week regimen consisting of daily, supervised, mild-moderate exercise as tolerated for 20 minutes, supervised, intermittent Finnish saunas (at about 140’F) sauna time with breaks and showers, gradually increased as tolerated to approximately 4 hours, dietary supplements including immediate release niacin in gradually increasing doses from 100 mg to a maximum of 5000 mg per day, salt and water, other vitamins, minerals and oils per Hubbard protocol.


Posted in: Clinical Trials, Religion

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How should we treat DCIS?

How should we treat DCIS?

I’ve written more times than I can remember about the phenomenon of overdiagnosis and the phenomenon that is linked at the hip with it, overtreatment. Overdiagnosis is a problem that arises when large populations of asymptomatic, apparently healthy people are screened for a disease or a condition, the idea being that catching the disease at an earlier stage in its progression will allow for more successful treatment. Two prominent examples include—of course—screening for breast cancer with mammography and screening for prostate cancer with prostate-specific antigen (PSA) testing, and I’ve written about the problem of overdiagnosis with each of them on many occasions. Basically, overdiagnosis occurs when the screening test picks up what we call “preclinical” disease (i.e., disease that hasn’t become symptomatic) that, if left untreated, would never become symptomatic or endanger the health or life of the patient). Although intuitively, it seems to the lay public (and, truth be told, most doctors) that detecting cancer earlier must be inherently better, it turns out that it’s way more complicated than you think. There is a price to be paid for early diagnosis in the form of overtreatment of disease that doesn’t need treatment and for disease that is destined to threaten the life of the patient earlier treatment doesn’t always result in better outcomes. Also, whenever you screen for a condition in asymptomatic people, you will always—always—find much more of it, and the significance of those added diagnoses is not always clear, as a new study in JAMA Oncology shows.

DCIS and mammography: Some background

Before I get to the meat of the study, from my perspective, nowhere is the problem of overdiagnosis and overtreatment in cancer screening as pronounced than in the condition known as ductal carcinoma in situ (DCIS). DCIS is commonly referred to as “stage 0″ breast cancer and is characterized by milk duct cells that appear malignant but remain confined to the milk ducts. In other words, they haven’t invaded the tissue surrounding the ducts. In general, DCIS is treated similarly to breast cancer, with surgical excision, either by mastectomy or breast-conserving surgery, followed by radiation therapy if breast conserving surgery is used. Then, depending on its hormone receptor status, adjuvant treatment consists of blocking estrogen for five years. The rationale for this treatment is the view of DCIS as being a precursor to fully invasive breast cancer and that treating the DCIS will prevent the development of breast cancer. Over the last couple of decades, however, it has become clear that not all DCIS is created equal. Much of it will never progress to breast cancer in the lifetime of the woman (particularly if the woman is older, which means less time for fully malignant transformation to occur). Evidence suggesting this includes studies showing an increase in DCIS incidence by 16-fold since the 1970s, when mammography started to be introduced on a large scale, with little change in the incidence of invasive cancer. Today, 20-25% of mammography-detected breast cancer diagnoses are DCIS; forty years ago, DCIS was an uncommon diagnosis, except associated with an invasive cancer.

Posted in: Basic Science, Cancer, Clinical Trials, Science and the Media

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An Alternative to Appendectomy: Antibiotics

An appendix, mid-appendectomy.

An appendix, mid-appendectomy.

My title doesn’t refer to alternative medicine, it refers to an alternative within medicine: treating appendicitis with antibiotics instead of surgery. You may be surprised to learn that patients with appendicitis don’t always automatically need an appendectomy. A recent randomized controlled trial in Finland compared surgery to medical treatment.

History of appendicitis treatment

There is an excellent, detailed history of appendicitis available online, complete with anecdotes illustrating its importance. The appendix was not mentioned in early anatomical studies, probably because they were done on animals that didn’t have an appendix. The organ was first described in 1521. The existence of appendicitis (called “typhlitis” until 1886) was gradually recognized during the 19th century, and by the end of that century surgical removal of the appendix had become the standard treatment. Walter Reed, the yellow fever researcher for whom the Army hospital was named, died of a ruptured appendix. King Edward VII’s coronation was delayed while he underwent a life-saving appendectomy.

Appendectomy predated antibiotics, and it was believed that appendicitis would invariably progress to perforation. Once antibiotics were available, doctors experimented with treating appendicitis with them instead of with surgery, starting as early as 1956. The published trials had limitations, so the new study was done to try to get a more definitive answer to the question of whether the antibiotic approach was as effective as the surgical approach.


Posted in: Clinical Trials, Pharmaceuticals, Surgical Procedures

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The 21st Century Cures Act: The (Somewhat) Good, The (Mostly) Bad, and The (Very) Ugly

The 21st Century Cures Act: Unnecessary and misguided.

The 21st Century Cures Act: Unnecessary and misguided.

The approval of new drugs and medical devices is a process fraught with scientific, political, and ethical landmines. Inherent in any such process is an unavoidable conflict between rigorous science and safety on the one side, which tend to slow the process down by requiring large randomized clinical trials that can take years, versus forces that demand faster approval. For example, patients suffering from deadly diseases demand faster approval of drugs that might give them the hope of surviving their disease, or at least of surviving considerably longer. This is a powerful force for reform, as evidenced by HIV/AIDS activism in the 1980s and 1990s that led to the development of fast-track approval mechanisms for drugs for life-threatening conditions, a change whose effects have been mixed. It’s also a powerful force potentially for ill, as I’ve documented in my posts about the understandable but misguided “right-to-try” movement. After all, what politician can say no to a constituency representing desperately ill people who only want a shot at survival? It’s not all desperate patients, however. Also wanting more rapid drug approval are powerful business interests in the form of the pharmaceutical and medical device industries, for whom the time and expense of prolonged clinical trials eat into profits and make some drugs not worth developing from a business standpoint.

In 1962, after Frances O. Kelsey, MD, PhD (who died on Friday at the age of 101) successfully prevented the approval of the drug thalidomide in the US, a drug found to cause serious birth defects, Congress passed the Kefauver-Harris Drug Amendments to the Federal Food, Drug, and Cosmetic Act. These amendments required that drug companies not just show safety before their drugs could be FDA-approved, as had been the case prior to the amendments, but also to provide substantial evidence of effectiveness for the product’s intended use. That evidence had to be in the form of adequate and well-controlled clinical trials, which at the time was considered a revolutionary requirement. (Believe it or not, no requirement for high quality clinical trials existed before 1962.) This led to the current system of phase I, II, III, and IV clinical trials in force in the United States today. The amendments also included a requirement for informed consent of study subjects and codified good manufacturing processes, as well as the requirement that adverse events be reported. This has been, with some tweaking over the years, the law of the land regarding how the FDA approves drugs for specific indications

Medicine is a lot more complex now than it was in the 1960s however, and there has been a growing sentiment that the system is, if not broken, at least functioning in a way that is behind the times, a manner that was acceptable and appropriate 40 years ago but is no longer so in this era of genomics, precision medicine (formerly known as “personalized medicine”), and targeted therapies. The new drug approval process, which can take up to a decade and cost a billion dollars, it is argued, is too rigid, cumbersome, and slow for the 21st century. (Why it wasn’t too rigid, cumbersome, and slow in the 20th century, no one seems to say. I guess that “21st century” sounds way cooler.)

Into this ongoing controversy have marched Rep. Fred Upton (R-Mich.) and Rep. Diana DeGette (D-Colo.), who have sponsored a bill passed by the House of Representatives in a rare display of bipartisanship in July. The bill, H.R.6, is entitled the “21st Century Cures Act“. Given how it passed the House by a vote of 344-77, one would think that it should glide through the Senate easily. Certainly, its sponsors and supporters have mounted a mighty PR effort. That might not be the case, given that in the Senate a single senator can hold up or even kill a bill through a filibuster, and to shut down a filibuster or prevent a threatened filibuster requires 60 votes. Be that as it may, I’m not so much interested in the politics of this bill, which, if it survives the Senate, will almost certainly be significantly amended, but rather what the bill does.

Posted in: Basic Science, Clinical Trials, Politics and Regulation

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The evolving story of the harms of anti-inflammatory drugs

Advil (ibuprofen)

Owing to summer vacation, today’s post updates a 2011 post and a 2013 post with some new information.

Anti-inflammatory drugs are among the most well-loved products in the modern medicine cabinet. They can provide good pain control, reduce inflammation, and eliminate fever. We give non-steroidal anti-inflammatory drugs (NSAIDs) in infancy, continuing through childhood and then adulthood for the aches and pains of modern living. It’s the later stages of life where NSAIDs are used most frequently, usually in the treatment of joint disease like osteoarthritis, which eventually affects pretty much everyone. Over 17 million Americans use NSAIDs on a daily basis, and this number will grow as the population ages. While they’re widely used, they also have a long list of side effects. Not only can they cause stomach ulcers and bleeding by damaging the lining of the gastrointestinal tract, cardiovascular risks are also significant.

It was the arrival (and withdrawal) of the drugs Bextra (valdecoxib) and Vioxx (rofecoxib) that led to a much better understanding of the potential for these drugs to increase the risks of heart attacks and strokes. And it’s now well-documented that these effects are not limited to the “COX-2″ drugs – almost all NSAIDs, including the old standbys we have used for years, raise the risk of heart attacks and strokes. (more…)

Posted in: Clinical Trials, Politics and Regulation, Science and the Media

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Ethical Failures



Me, ten minutes after the end of this post.  EXTREME!


It is summer vacation for me in Eastern Oregon at Sunriver. Unbelievable geology, fantastic hikes, great biking, wonderful golf, delicious beer and good food. The thesaurus fails me for superlatives. It is hard to get too riled up about all things SCAM to produce a blog entry when I could be doing one or all of the above. I really don’t want to do this. Sadly, David keeps threatening me with the video he has of me touting the benefits of Integrative Medicine with its holistic approach to health care, and I just can’t have that published on the ‘net. So some brief speculation to fill the time between golf and a pint of IPA overlooking the Sisters.

Ethics, and the purpose of SBM

Steve started this blog in 2008 in part because he realized that evidence-based medicine was inadequate for the task of evaluating pseudo-medicines. He coined the term ‘science-based medicine’ with the realization that for fantastical therapies like acupuncture or homeopathy, all the potential biases and flaws in the evidence from clinical studies could result in pseudo-medicines appearing effective when at heart they are all Oakland California.

I do not suppose there could be science-based ethics. One person’s ethical certainty is another’s belly laugh. I remember a grand rounds on human cloning years ago and they had, among others, a priest discussing the ethics of human cloning, and I thought at the time there would be few speakers with less legitimacy. And really, I can see no harm in cloning an army of zombie super soldiers, especially if they were under my control.

Still, one of the issues I remain amazed at is how many clinical trials testing pseudo-medicines are approved by institutional review boards (IRB). (more…)

Posted in: Clinical Trials, Ethics

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Update on Cholesterol and Statins

The statin hypothesis is that statins reduce cardiac risk more than can be explained by the reduction in LDL cholesterol. That hypothesis has been overturned by a new study.

The statin hypothesis is that statins reduce cardiac risk more than can be explained by the reduction in LDL cholesterol. That hypothesis has been overturned by a new study.


The consensus of mainstream medicine is that a high blood level of LDL cholesterol is a major risk factor for cardiovascular disease and that lowering high levels can help with prevention and treatment. Statins have been proven effective for lowering cholesterol levels and for decreasing cardiovascular and all-cause mortality. I recently wrote about the new guidelines for statin therapy.

Currently half of American men between the ages of 65 and 74 are taking statins, and 71 percent of adults with heart disease and 54 percent of adults with high cholesterol take a cholesterol-lowering drug.

There is still a fringe group of a few maverick “cholesterol skeptics” who think lowering cholesterol is useless or counterproductive, but the evidence shows they are wrong.


Posted in: Clinical Trials

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Chiropractic and Stroke: The question is not answered

Extreme rotation of the atlas on the axis (at the atlantoaxial joint) stretches the vertebral artery.  In layman's terms, 40% of a hanging.

Extreme rotation of the atlas on the axis (at the atlantoaxial joint) stretches the vertebral artery. In layman’s terms, 40% of a hanging.

I am off to Chicago for 5 days to wow the SMACC crowd with my ID/SBM acumen. I hope. Given that most of my multiple-personalities do not seem to be able to get any work done, I am forced to write a brief post this week, limited by the battery life on my MacBook Air. Whatever I get down on paper? pixels? RAM? before the battery dies as I fly over the Rockies will be the post. It is times like this I wish I had Gorskian typing skills.

SBM has discussed the many limitations of chiropractic: the low grades for entry into chiropractic school, the inadequate training, their reason d’être, subluxations and their adjustments being divorced from reality, the lack of efficacy of chiropractic for any process beyond low back pain (and even that is no better than safer interventions), the fondness of chiropractors for other useless pseudo-medicines, and their opposition to vaccines.

Hm. When I put it like that chiropractic does appear a little sketchy. But is chiropractic safe? It is a hands-on intervention, for a brief period of time applying the same force to the neck as about 40% of hanging from the neck until dead. So there is certainly the potential for chiropractic to cause harm. (more…)

Posted in: Chiropractic, Clinical Trials

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Homeopathic industry and its acolytes make poor showing before FDA

Ask your pharmacist if nothing is right for you. (HT @leachkathleen)

Ask your pharmacist if nothing is right for you. (HT @leachkathleen)

On April 21 and 22, the FDA held a public hearing:

to obtain information and comments from stakeholders about the current use of human drug and biological products labeled as homeopathic, as well as the Agency’s regulatory framework for such products. . . . FDA is seeking participants for the public hearing and written comments from all interested parties, including, but not limited to, consumers, patients, caregivers, health care professionals, patient groups, and industry.

The FTC recently announced that it, too, is wading into the homeopathic waters. The FTC, which regulates advertising of homeopathic products, will hold a public workshop on September 21 in Washington, DC, “to examine advertising for over-the-counter (OTC) homeopathic products.” Like the FDA, it will also accept public comments online.

All of this regulatory buzz caused the FDA Law Blog to take notice. (The blog is hosted by a law firm specializing in food and drug regulation law.) A post titled “Will FTC Kill Homeopathic Products – or Will FDA?” gave this assessment:

Bottom line, if the FTC holds homeopathic products to the same scientific standards that are applied to claims for other OTC products like dietary supplements, as the FTC appears inclined to do . . . few if any homeopathic products will pass the test.


Posted in: Clinical Trials, Health Fraud, Homeopathy, Legal, Naturopathy, Politics and Regulation

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As in 2014, “right-to-try” laws continue to metastasize in 2015, part 2

As in 2014, “right-to-try” laws continue to metastasize in 2015, part 2

When I wrote a week ago about the sham that is “right-to-try”, one criticism (among many) that I made of these misguided, profoundly patient-unfriendly laws was that I have as yet been unable to find a single example of a patient who has managed to obtain access to an experimental therapeutic through such a law, much less been helped by it. So-called “right-to-try” laws, of course, claim to provide a mechanism by which patients with terminal illnesses can obtain access to experimental therapeutics not yet approved by the FDA but still in clinical trials. They are, as I’ve pointed out, a cruel sham, placebo legislation that makes lawmakers feel as though they’ve done something good but do nothing of substance for patients while providing them with false hope. The federal government through the FDA controls drug approval, which means that states can’t compel a drug company to provide a drug to a patient, and most drug companies would not want to risk jeopardizing approval of their drug, which is what could happen if they grant access to an investigational drug under right-to-try and the patient suffers an adverse event. After all, the success rate for drugs that have passed phase 1 (which is all that right-to-try requires) in phase 3 trials is only on the order of 9-12%, meaning that that’s the most optimistic probability that such drugs would benefit a patient. In reality, it’s almost certainly much, much lower.

Posted in: Clinical Trials, Politics and Regulation

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