I often worry that I am too hard on clinicians, mocking them for their credulity and innumeracy. Medicine is hard, and I would much rather be treated by a doctor who is innumerate and a careful listener than one who knows the difference between a standard error and a standard deviation but doesn’t listen to a word I say.
And then I read articles like this one (Clinical Indications and Compassionate Use of Phage Therapy: Personal Experience and Literature Review with a Focus on Osteoarticular Infections), and I repent my resolution to be more generous.
The authors, who are mostly French, pose a very reasonable question in the abstract:
The few formal experimental phage clinical trials that have been completed to date have produced inconclusive results on the efficacy of phage therapy, which contradicts the many successful treatment outcomes observed in historical accounts and recent individual case reports. It would therefore be wise to identify why such a discordance exists….”
It would indeed be wise. The most obvious possibility, at least to my ungenerous mind, is publication bias: observational studies with positive results are nearly four times as likely to be published as studies with negative results. The same analysis showed no bias for randomly controlled trials.
Lots of people are interested in hearing about a promising new therapy; no one wants to hear about failure. Phage therapy curing a patient at death’s door is a great story; a patient dying from a bacterial infection despite extraordinary efforts is, sadly, not news at all. It would be remarkable if there were no publication bias among case histories of phage therapy.
Patey et al don’t consider publication bias as an explanation for the discrepancy between RCT and case study outcomes. They are confident that they know when and where and how PT works, and so the question is really why it isn’t used more.
They light on regulatory barriers as the culprit.
Many researchers and medical doctors have voiced the need to revise the regulatory classification of phage therapy products … as a drug by the Food and Drug Administration (FDA) in the United States, which necessitate that phages be produced under Good Manufacturing Practice (GMP) guidelines and infrastructure
Oh, the horror!
I get it that academic labs and clinicians might be intimidated by implementing GMP. But that’s ignorance talking, and there is no reason we should pay attention. GMP is simply about creating a manufacturing process that is reliable and traceable. It means writing out detailed procedures, ensuring that equipment is properly maintained, ensuring that the people doing the work are adequately trained, verifying product quality, and monitoring the whole process to catch and prevent errors.
That really doesn’t seem like too much to ask for a product that treats serious diseases. Even though phage are extraordinarily safe (much more than most small molecule drugs) you’d still like to have some assurance that what you are giving to patients does what it is supposed to do.
Implementing GMP is hard work to be sure, but it’s just work. No breakthroughs are required, no magic is involved. We did it for a bacteriophage-based diagnostic product at MicroPhage. It can be done for therapeutic products. If GMP implementation was all that was standing between success and failure for phage therapy, we would have many, many successes and far fewer failures.
The greater barrier to success is intellectual laziness. We don’t need to relax regulations. We do need smart, disciplined thinkers committed to solving the considerable practical barriers to implementing phage therapy. These seem to be in remarkably short supply.