Category: Ethics

Rather, they’re the best fake medicine.

This is a mildly entertaining review of placebo responses from migraine trials, looking to compare the effect size of various forms of placebo.  These authors identified 79 studies with appropriate response-to-therapy data for analysis, and evaluated the relative influences of pharmacologic therapy, cognitive-behavioral therapy, and acupuncture or surgery versus their placebo/sham versions.

Sham cognitive-behavioral therapy was ineffective and all the confidence intervals crossed unity.  Pharmacologic placebo was only superior to no treatment at all.  Then, sham acupuncture or surgery was superior to both no treatment and pharmacologic placebo.  Hence, the authors conclude the expectation of benefit is enhanced by the elaborate rituals associated with invasive therapies – and ought to be considered and cautioned against when designing trials that attempt comparisons between invasive and medical therapies.

Or, you could simply use this knowledge for evil – and conduct almost guaranteed-success non-inferiority trials for any manner of medically useless device for provision of symptom relief.

The choice is yours.

“Differential Effectiveness of Placebo Treatments: A Systematic Review of Migraine Prophylaxis”
http://www.ncbi.nlm.nih.gov/pubmed/24126676

Placebo mechanisms are well-known.  As Ken Milne of The Skeptic’s Guide is happy to tell you, the power of belief is strong.

But, it turns out it can be made stronger.

This rather fascinating study evaluates the power of oxytocin.  Oxytocin has been linked to processes of empathy, trust, and social learning.  These elements, as noted by the authors, are key to patient-physician interactions.  So, they perform a little study to see whether oxytocin can enhance the placebo effect – tapping into the elements of physician empathy and trust.

In the experiment, a technician applied either oxytocin or saline intranasally.  Then, they applied the same inert cream to two sites on each patient’s forearm, telling the patient one was the control, and one was the active drug.  Patients were tested using heat as painful stimuli on a visual analog scale.

There was, as expected, a placebo effect.  In the saline group, the mean VAS difference between the inert “control” cream and the inert “placebo” cream was 7mm.  In the oxytocin group, however, the mean VAS difference between sites was 13mm.  In their small group of patients, this result met statistical significance – and thus the authors conclude oxytocin enhances the placebo response.

Not precisely certain how this would be applied clinically, but it’s a fascinating little research letter.

“Effect of Oxytocin on Placebo Analgesia: A Randomized Study”
http://www.ncbi.nlm.nih.gov/pubmed/24150470

There are many challenges in the world of scientific publishing.  I’ve spent time focusing on conflict-of-interest in peer review – but this is a fabulous exposé on a rapidly-growing segment of for-profit, predatory journals with no substantial peer-review process whatsoever.

This is more a journalistic project than a scientific study, but it details the results of an experiment performed to determine the rigor of peer review at a number of open-access journals.  Open access journals, in contrary to most journals, derive their operating income by charging authors a publication fee – rather than charging for print subscription, reprints, or individual article access.  Proponents of this model point to the beneficial effect open-access has on medical knowledge in countries without the means and wealth required to join the first-world scientific community.  However, this model has essentially been hijacked by editors who use a predatory process of fraudulent representation to run these journals solely for profit.

This journalist created a fake, flawed, and horribly written (he ran it through Google Translate into French, and back) molecular cancer therapeutics article and submitted it to over 300 open-access journals – half these journals were on a “blacklist” and the remainder were not.  Without completely re-iterating the entire story (or the mystery of Grace Groovy), the crux is – nearly every journal on the “blacklist” accepted the fictional article, while journals on the more reliable list rejected it about 2/3rds of the time.

Lovely piece of investigative journalist and an entertaining read – and an excellent description of a growing problem in the realm of scientific integrity.

“Who’s Afraid of Peer Review?”
http://www.sciencemag.org/content/342/6154/60.summary

As if we didn’t have enough difficulty interpreting results when study design is inadequate, blinding is violated, sample sizes are underpowered, or there are differences in enrollment – we must also be worried about gross scientific misconduct.

This concerns the Jikei Heart Study and the Kyoto Heart Study – evaluations of valsartan conducted and published in 2007 and 2009, respectively.  In short, a series of investigations into the integrity of the studies revealed the following, as quoted:

“We believe, therefore, that the data were intentionally altered.”

and

“We suspect that the data were altered during their statistical analysis.”

The Lancet, in their retraction notice, note specific challenges in following up and identifying the affiliation for the study statistician, who appeared to not disclose his employment by Novartis.

When the stakes are high, the temptation to use every potential advantage to generate favorable study results is simply too great.  Jeffrey Drazen has asked us to “Believe the Data” – I think the onus is on those who generate the data to earn our trust.

“Retraction—Valsartan in a Japanese population with hypertension and other cardiovascular disease (Jikei Heart Study): a randomised, open-label, blinded endpoint morbidity-mortality study”
http://www.ncbi.nlm.nih.gov/pubmed/24012258