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Posts Tagged clinical trials

False balance about Stanislaw Burzynski and his disproven cancer therapy, courtesy of STAT News

Stanislaw Burzynski: 40 years of failure to prove that his antineoplastons are effective against cancer.

Stanislaw Burzynski: 40 years of failure to prove that his antineoplastons are effective against cancer.

One common theme that has been revisited time and time again on this blog since its very founding is the problem of how science and medicine are reported. For example, back when I first started blogging, years before I joined Science-Based Medicine in 2008, one thing that used to drive me absolutely nuts was the tendency of the press to include in any story about vaccines an antivaccine activist to “tell the other side” or to “balance” the story. So in a story on vaccines, on one side you would have Paul Offit, a bona fide, legitimate vaccine expert, and on the other side you would have J.B. Handley, Jenny McCarthy, Andrew Wakefield, or a lesser light of the antivaccine movement. This same trope included stories about autistic children in which a reporter does a human interest story about a family struggling with raising an autistic child in which he lets the parents spout antivaccine misinformation, providing only a brief token quote by a scientist for “balance.” Thus, whether they intended it or not, the reporter would let the emotional impact of the story serve as persuasion to believe the parents’ antivaccine views. So, even though there was not (and hasn’t been at least since 2001 or probably much earlier) anything resembling legitimate scientific controversy over the question of whether vaccines cause or contribute to autism, the press aided the antivaccine movement in keeping alive the appearance of a controversy. It was, as I like to call these things, a manufactroversy, a controversy manufactured by the antivaccine movement to give the appearance of an actual scientific controversy. It’s a time-dishonored journalistic failing that is still a major problem with reporting on, for example, anthropogenic global climate change and genetically modified organisms (GMOs).

Sometimes, however, the press is teachable. A few years ago, after already having blogged about vaccines and autism for several years, I started noticing fewer stories with false “balance” and more stories that simply treated the antivaccine movement like the fringe movement it was, either not bothering to mention it or, if it had to mention it, basically letting scientists explain why it’s bad science and dangerous to public health. These days, false balance and stories that are antivaccine propaganda are relatively rare, aside from stories by fringe journalists like Sharyl Attkisson and Ben Swann. That’s a good thing. Unfortunately, I wish I could say that I really believe it was due to the efforts of skeptics and science advocates more than it was due to the discrediting of a major antivaccine figure, Andrew Wakefield, but even six years after Wakefield lost his medical license and saw his infamous 1998 Lancet paper linking the MMR vaccine to bowel disease in autistic children (the one that ignited the MMR scare in the UK) retracted, I’m not entirely sure. Be that as it may, there still remain blind spots in the press. (more…)

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

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The hijacking of evidence-based medicine

One of our heroes at SBM: John Ioannidis.

One of our heroes at SBM: John Ioannidis.

It’s no secret that I’m a fan of John Ioannidis. So, I daresay, are pretty much all of the editors and regular contributors to this blog. (If you don’t believe me, just type Ioannidis’ name into the blog search box and see how many posts you find.) Over the last couple of decades, Ioannidis has arguably done more to reveal the shortcomings of the medical research enterprise that undergirds our treatments, revealing the weaknesses in the evidence base and how easily clinical trials can mislead, than any other researcher. Indeed, after reading what is Ioannidis’ most famous article, “Why Most Published Research Findings Are False“, back in 2005, I was hooked. I even used it for our surgical oncology journal club at the cancer center where I was faculty back then. This was long before I appreciated the difference between science-based medicine (SBM) and evidence-based medicine (EBM). So it was with much interest that I read an article by him published last week and framed as an open letter to David Sackett, the father of evidence-based medicine, entitled “Evidence-based medicine has been hijacked: a report to David Sackett.” Ioannidis is also quoted in a follow-up interview with Retraction Watch.

Before I get to Ioannidis’ latest, I can’t help but point out that, not surprisingly, quacks and proponents of pseudoscientific and unscientific medicine often latch on to Ioannidis’ work to support their quackery and pseudoscience. They’ve been doing it for years. Certainly, they’re already latching on to this article as vindication of their beliefs. After all, their reasoning—if you can call it that—seems to boil down to: If “conventional” medicine is built on such shaky science, then their pseudoscience isn’t wrong after all, given that the same scientific enterprise upon which conventional medicine is based produces the findings that reject their dubious claims and treatments. Of course, whenever I hear this line of argument, I’m reminded of Ben Goldacre’s famous adage, seen in one form on Twitter here:

The adage can be generalized to all EBM and SBM as well. Just because big pharma misbehaves, EBM has flaws, and conventional medicine practitioners don’t always use the most rigorous evidence does not mean that, for example, homeopathy, acupuncture, or energy medicine works.

Still, when Ioannidis publishes an article with a title provocatively declaring that EBM has been “hijacked,” we at SBM take notice. (more…)

Posted in: Basic Science, Clinical Trials, Medical Academia, Pharmaceuticals, Politics and Regulation

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Reporting results from clinical trials is vital for science-based medicine

Real medicine is built on high quality data. That’s one lesson I learned through my rehabilitation as a former naturopath. I can assure you that this principle does not apply to naturopathy or any of the other types of alternative medicine, which are mostly based on anachronistic traditions, magical thinking, and poor academic integrity. I now know that real medicine incorporates any therapy scientifically demonstrated to be effective and safe, regardless of origin. Therapies that fail to demonstrate effectiveness remain alternative for good reason.

I made a sharp turn in my career when I realized this, but I was recently surprised to learn that a failure to respect the data can sometimes also characterize medicine. I’m not trying to fool anyone with an appeal to hypocrisy (often used by alternative medicine zealots to argue that their beliefs are somehow valid simply because medicine has problems). But I do want to draw attention to a problem with medical research, which has the potential to undermine science-based medicine and take us down the dark path of misinformed medicine — medicine based on incomplete data.

pills

Most people probably don’t realize that a majority of clinical trials do not report their findings.[1–3] About half of trials conducted before 2007, before it was legally required to register and report clinical trials, have never been published.[4, 5] Even since stronger legal mandates were enacted, most clinical trials still are not registered or reported.[1–3] As a result, there is a huge amount of clinical data unknown to the medical community and not available to clinicians or patients.

This effectively means that medical decisions can be based on incomplete information, not only diminishing the effectiveness of treatments but also eroding the perceived plausibility of medical interventions over time. This is what Sense About Science’s AllTrials campaign is all about: ensuring that all clinical trials register and report results in a publicly-available database. I see it as an obvious and straightforward means to improve medicine. (more…)

Posted in: Clinical Trials, Ethics, Naturopathy, Politics and Regulation, Quality Improvement, Science and Medicine

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Worshiping at the altar of the Cult of the Brave Maverick Doctor

Death of Cancer

One of my favorite television shows right now is The Knick, as I described before in a post about medical history. To give you an idea of how much I’m into The Knick, I’ll tell you that I signed up for Cinemax for three months just for that one show. (After its second season finale airs next Friday, I’ll drop Cinemax until next fall.) The reason why I’m bringing up The Knick (besides I love the show and need to bring it up at least once a year) is because an article by Malcolm Gladwell in The New Yorker entitled “Tough Medicine“, which is a commentary based on a new book on cancer by a veritable god of cancer research, Vincent T. DeVita, Jr., immediately resonated with a storyline in this season of The Knick. I haven’t yet read The Death of Cancer: After Fifty Years on the Front Lines of Medicine, a Pioneering Oncologist Reveals Why the War on Cancer Is Winnable–and How We Can Get There by Vincent T. DeVita and Elizabeth DeVita-Raeburn, but I want to. I can tell, though, that there will be parts of the book I find annoying just from Gladwell’s take on it, which approvingly describes DeVita as railing against the cautiousness and incremental nature of today’s cancer research. To give you an idea of where Gladwell’s coming from, I note that his article shows up in the title bar of my web browser not as “Tough Medicine” but rather “How To Cure Cancer”, even as the title on the web page itself remains “Tough Medicine”. On the other hand, the article does conclude with Gladwell demonstrating a better understanding of the disadvantages of what DeVita is proposing than it seems that he will in the beginning. In fact, it is Gladwell who is more reasonable than his subject, although he does appear share DeVita’s apparent assumption that potentially all cancer patients are savable if only we try hard enough. (more…)

Posted in: Cancer, Clinical Trials, History, Medical Ethics

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Stanislaw Burzynski and Robert O. Young: How two quacks of a feather illustrate how poorly states regulate medical practice

Stanislaw Burzynski (upper panel) and Robert O. Young (lower panel), two quacks whose activities reveal the weaknesses in how the practice of medicine is regulated.

Stanislaw Burzynski (upper panel) and Robert O. Young (lower panel), two quacks whose activities reveal the weaknesses in how the practice of medicine is regulated.

One of the weaknesses in our system of regulating the practice of medicine in the United States is that, unlike most countries, we don’t have one system. We have 50 systems. That’s because the functions of licensing physicians and regulating the practice of medicine are not federal functions, but state functions. Each state sets its own laws and regulations governing the practice of medicine, making for wide variability from state to state. Some states are lax in their regulation (cough, cough, I’m talking to you, Texas), others are not so lax.

Given how often state medical boards and the other enforcement bodies states use to protect the public from professional misconduct and quackery, I thought I’d take this opportunity to update our readers on two men who have been frequent topics of discussion on this blog, Stanislaw Burzynski and Robert O. Young. The reason is that, through some bizarre confluence of events, both of them faced justice last week, in the form of a hearing due to action against Burzynski by the Texas Medical Board, and in the form of the trial of Robert O. Young in southern California.

What these two quacks share in common is that they’ve gotten away with their cancer quackery for a very long time, two decades in the case of Robert O. Young and nearly four decades in the case of Stanislaw Burzynski, with attempts by the law to bring them to heel having been largely ineffective. They are different in that one is a physician (Dr. Burzynski) and one is not (Young) and therefore different legal considerations come into play. Young, for instance, is a self-proclaimed naturopath known for his “pH Miracle Living” cure, which, he claims, can be used to cure basically any disease by “alkalinizing” the body. After two decades of running, he is being tried for practicing medicine without a license, and, of course, fraud. Burzynski, although not an oncologist, is a licensed physician in Texas and has been administering an unproven and almost certainly ineffective “natural” treatment consisting of substances derived from blood and urine that he dubbed “antineoplastons” (ANPs) back in the 1970s. He is also different in that he’s gotten away with this largely through abuse of the clinical trial process, which is regulated at the federal level through the FDA and the HHS. It is not, however, the federal government that is pursuing action against Burzynski, but rather the Texas Medical Board (TMB). Thus, while Young is on trial and could go to jail if he loses, if Burzynski loses he will only lose his license to practice medicine in the state of Texas.

Despite their differences, both Stanislaw Burzynski and Robert O. Young illuminate major shortcomings in how the legal system deals with quacks.
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Posted in: Health Fraud, Politics and Regulation

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Acupuncture/TCPM Crapfest

Acupuncture needling

Look Ma! No gloves!

As I get older I get more grumpy. Issues that at one time I was rather sanguine about, now irritate the hell out of me. It is not like it was when I started practice. Information was hard to come by. Going through the Index Medicus, with the world’s tiniest font, wandering the stacks looking for papers, sending off for reprints, getting a precious Xerox (or even a mimeograph) of a classic paper from an attending.

You understood the value of eminence-based medicine, as it took a career to acquire and master the literature. You relied on the wisdom of old geezers like me who had decades of experience and reading.

That was then. Now? The world’s information is available almost instantaneously. You may not be able to master a new topic spending a day on Google and Pubmed, but you can acquire a reasonable understanding, especially of you have some background.

Because of Google and Pubmed, the only reasons for ignorance of your area of expertise in medicine are time, laziness, or stupidity. As a specialist, only time is an excuse. It is my job to keep up with infectious diseases, although with over 10,000 articles a year in ID, it is impossible to read everything. But if I have a question concerning patient care, I need to look it up. I have another blog whose raison d’être is looking up answers to the daily questions that arise in practice.

On the characteristics of a useful clinical trial

So the characteristics of a useful clinical trial are not hard to determine: Randomized, double blind, placebo controlled, adequately powered. Because you want to avoid spending time and money on a study only to end up with no useful conclusions. This is especially important with acupuncture where it not does matter what kind of acupuncture is used, if needles are used, where the needles are placed or even if you mime acupuncture or perform acupuncture on a rubber hand. The key features for success in acupuncture are belief that the patient is receiving acupuncture and that the patient believes the acupuncture will be effective. And the stronger the belief, the better the subjective response. (more…)

Posted in: Acupuncture, Clinical Trials, Traditional Chinese Medicine

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

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

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

Last year, I did several posts on what I consider to be a profoundly misguided and potentially harmful type of law known as “right-to-try.” Beginning about a year and a half ago, promoted by the libertarian think tank known as the Goldwater Institute, right-to-try laws began popping up in state legislatures, which I likened to Dallas Buyers Club laws. Both Jann Bellamy and I wrote about how these laws are far more likely to do harm than good, and that is a position that I maintain today. The idea behind these laws is to give terminally ill patients access to experimental drugs—in some cases drugs that have only passed phase I testing—that might help them. It’s an understandable, albeit flawed argument. After all, it’s perfectly understandable why terminally ill patients would fight for drugs that give them hope, and it’s just as understandable why politicians and the public would see such a goal as a good thing. In practice, as I will explain again in the context of this update, such laws are far more likely to harm patients than help them. Indeed, as you will see, in the year since the first wave of right-to-try laws have passed, not a single patient that I can find has obtained access to experimental drugs under a right-to-try law, much less been helped by them.

Unfortunately, given how effectively “right to try” has been sold on grounds of providing terminally ill patients hope and as a matter of personal freedom, it’s clear that this wave is not going to abate. Since Colorado passed the very first right-to-try law almost exactly a year ago today, a total of 17 more states now have passed passed similar legislation, the most recent being Tennessee, and 22 others have introduced legislation. It’s a good bet that right-to-try will pass in all of those states, because, as I’ve explained many times before and in many interviews, if you don’t understand clinical trial ethics and science, opposing the concept of right-to-try comes across like opposing Mom, apple pie, and the American flag. It also leaves opponents open to false—but seemingly convincing—charges of callousness towards the terminally ill on the order of taking pleasure from drop kicking yipping puppies through flaming goalposts. (I exaggerate, but only slightly, I assure you.)
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Posted in: Clinical Trials, Pharmaceuticals, Politics and Regulation

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Mediocre Expectations

Pictured: Relevant.  Oh yeah, it's going to get weird. Image courtesy of the Wellcome Trust Image Library via the Wikimedia Commons.

Pictured: Relevant. Oh yeah, it’s going to get weird.

I had a dickens of a time writing this entry. The last week has been spent in New York for NECSS. It is safe to say that New York has plenty of distractions for us Dug the Dog types. Reality may be a honey badger, but New York is a squirrel. I say that when I travel I usually do not come across food better than I can find in Portland. Nope. Not true of New York. It joins Paris and New Orleans in the holy trinity of good eats, although I will stick with Pacific Northwest beer. And the rule is that for every day you are gone, three days’ worth of work piles up. I really need to stop taking time off.

I spoke at NECSS on a favorite topic of mine, how acupuncture works. It doesn’t. But I discussed a few studies that I found interesting. Like all studies, no single paper is definitive. The third law of the medical literature states that for every study, there is an equal and opposite study. A bit of an exaggeration perhaps but I do find the direction that the following studies point interesting both as to acupuncture’s mechanism of inaction and how the mind functions, making them worth collecting in an essay. (more…)

Posted in: Science and Medicine

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