Archive for Clinical Trials

October is National Chiropractic Health Month!

October is National Chiropractic Health Month (NCHM) and chiropractors can’t resist the opportunity to overstate, obfuscate, and prevaricate in celebration.

They do this in the face of some unfortunate (for them) statistics revealed by a recent Gallup Poll. The Poll was paid for by Palmer College of Chiropractic as part of an effort to increase the chiropractic share of the health care pie. (There is also a secondary analysis of the poll in the Journal of Manipulative and Physiological Therapeutics.) We’ll get to those stats in a few minutes.

But first, in celebration of NCHM, the American Chiropractic Association (ACA) has produced a set of six graphics chiropractors can download and display. Four of them fudge on the facts. Let’s take a look at these graphics, compare them to the evidence cited in support of their claims, and see where the ACA went astray. (The ACA also hosted a twitter chat yesterday with the hashtag #PainFreeNation.)


The study cited as evidence for this graphic actually compared both manual thrust manipulation (MTM) and mechanical-assisted manipulation (MAM) to each other as well as manipulation versus usual medical care (UMC). Although MAM, such as the Activator Method, is the second most common manipulation technique used by American chiropractors, is increasing in popularity among them, and is touted to be a safe and effective alternative to MTM, this study found that MTM is more effective (at 4 weeks) than MAM and that MAM had no advantage over UMC. But you don’t see that in this graphic.


Posted in: Chiropractic, Clinical Trials, Critical Thinking

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The Worst Homeopathy Study. Ever

A rare double-face palm, so you can't see the tears

A rare double-face palm, so you can’t see the tears

I run across a lot of information in my feeds that I need to save for further evaluation. The study “Does additional antimicrobial treatment have a better effect on URTI cough resolution than homeopathic symptomatic therapy alone? A real-life preliminary observational study in a pediatric population“, I saved with the file name, ‘jaw droppingly stupid’.

The worst homeopathy clinical trial ever doesn’t spring full formed like Athena from the head of Zeus. No. The worst homeopathy clinical trial ever started with a seed. The seed is “Homeopathic medicine for acute cough in upper respiratory tract infections and acute bronchitis: A randomized, double-blind, placebo-controlled trial, which is a standard lousy homeopathic study. (more…)

Posted in: Clinical Trials, Ethics, Homeopathy

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Battle of the feds: FTC tells FDA to do its job regulating homeopathy

Two institutions duke it out: FTC vs FDA.

Two institutions duke it out: FTC versus FDA.

Last month, the Society for Science-Based Medicine submitted a comment to the Food and Drug Administration (FDA) in response to its request for public comments on the agency’s current regulation (actually, lack of regulation) of homeopathic drugs. As the SFSBM pointed out, the FDA has, without legal authority, exempted homeopathic drugs from the safety and efficacy requirements applicable to other drugs under the Food, Drug and Cosmetic Act (FD&C Act). Lax regulation has resulted in consumer confusion: consumers do not understand homeopathy, how the FDA regulates homeopathic drugs, and the lack of scientific evidence underlying claims made by homeopathic drug companies.

As it turns out, we were in excellent company. The Federal Trade Commission (FTC), the agency charged with preventing fraudulent and deceptive business practices, submitted its own comment to the FDA, making these same points. (The FTC is holding its own workshop on advertising homeopathic drugs later this month. We’ll get to that shortly.)

The FTC’s advertising substantiation policy requires that health-related efficacy claims be supported by competent and reliable scientific evidence. The FDA, despite federal law, does not require evidence of efficacy for homeopathic drugs prior to their being marketed. This creates a potential conflict between the two regulatory schemes, resulting in homeopathic over-the-counter (OTC) “drugs” on the market that both comply with FDA’s policy and violate FTC’s policy. This, says the FTC, can be harmful to consumers and create confusion for advertisers. The FTC “recommends that the FDA reconsider its regulatory framework for homeopathic medicines” and tells the FDA what it can do to remedy the situation. (more…)

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

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“Precision medicine”: Hope, hype, or both?

The cost to sequence a whole genome has been plummeting impressively since 2007.

The cost to sequence a whole genome has been plummeting impressively since 2007.

I am fortunate to have become a physician in a time of great scientific progress. Back when I was in college and medical school, the thought that we would one day be able to sequence the human genome (and now sequence hundreds of cancer genomes), to measure the expression of every gene in the genome simultaneously on a single “gene chip,” and to assess the relative abundance of every RNA transcript, coding and noncoding (such as microRNAs) simultaneously through next generation sequencing (NGS) techniques was considered, if not science fiction, so far off in the future as to be unlikely to impact medicine in my career. Yet here I am, mid-career, and all of these are a reality. The cost of rapidly sequencing a genome has plummeted. Basically, the first human genome cost nearly $3 billion to sequence, while recent developments in sequencing technology have brought that cost down to the point where the “$1,000 genome” is within sight, if not already here, as illustrated in the graph above published by the National Human Genome Research Institute. Whether the “$1,000 genome” is truly here or not, the price is down to a few thousand dollars. Compare that to the cost of, for instance, the OncoType DX 21-gene assay for estrogen receptor-positive breast cancer, which costs nearly $4,000 and is paid for by insurance because its results can spare many women from even more expensive chemotherapy.

So, ready or not, genomic medicine is here, whether we know enough or not to interpret the results in individual patients and use it to benefit them, so much so that President Obama announced a $215 million plan for research in genomic mapping and precision medicine known as the Precision Medicine Initiative. Meanwhile, the deeply flawed yet popular 21st Century Cures bill, which passed the House of Representatives, bets heavily on genomic research and precision medicine. As I mentioned when I discussed the bill, it’s not so much the genomic medicine funding that is the major flaw in the bill but rather its underlying assumption that encouraging the FDA to decrease the burden of evidence to approve new drugs and devices will magically lead to an explosion in “21st century cures,” the same old antiregulatory wine in a slightly new bottle. Be that as it may, one way or the other, the federal government is poised to spend lots of money on precision medicine.

Because I’m a cancer doctor, and, if there’s one area in medicine in which precision medicine is being hyped the hardest, it’s hard for me not to think that the sea change that is going on in medicine really hit the national consciousness four years ago. That was when Walter Isaacson’s biography of Steve Jobs revealed that after his cancer had recurred as metastatic disease in 2010. Jobs had consulted with research teams at Stanford, Johns Hopkins, and the Broad Institute to have the genome of his cancer and normal tissue sequenced, one of the first twenty people in the world to have this information. At the time (2010-2011), each genome sequence cost $100,000, which Jobs could easily afford. Scientists and oncologists looked at this information and used it to choose various targeted therapies for Jobs throughout the remainder of his life, and Jobs met with all his doctors and researchers from the three institutions working on the DNA from his cancer at the Four Seasons Hotel in Palo Alto to discuss the genetic signatures found in Jobs’ cancer and how best to target them. Jobs’ case, as we now know, was a failure. However much Jobs’ team tried to stay one step ahead of his cancer, the cancer caught up and passed whatever they could do. (more…)

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

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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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