First, here is a short story. I have been seeing my current hepatologist for about 3 yrs now. Recently, the clinic hired a new nurse, pretty, sweet, very knowledgeable and she checked me during each of my following visit. Since then, my numbers steadily go down. Should I say she is an effective treatment for my PSC? The positive result is obvious and it correlates well with her presence at the clinic. And it has been like that for about 4 months now. You will say no, that’s not true. I agree with you. That’s the spontaneous fluctuation of blood test, common in PSC patients. How can we avoid that misleading interpretation in our research? A carefully designed study! All confounding factors should be considered, age, gender, ALP response to Urso, etc.. Otherwise, the conclusion will not be convincing. That’s my take of Cox’s study. For example, there are plenty of studies showing the difference between peds and adults PSC patients. If you include both patients in one group, then you have to consider how that difference would affect the response to vancomycin as a whole. A better way to do it, is that you either separate them or increase subject numbers in each group. It’s just a simplified statement. It might be more complicated than that.
Current studies do show the potential of vancomycin to be an effective treatment for PSC. That’s about it. Any extrapolation beyond that should be very careful. There is no simple yes or no if you decide to use it. We just don't know the answer. To further explore this treatment, we need a better designed research, not just new tools. If the design is flawed, fancy test won’t help. Initial Fox’s study is just a case report. Then there is Lindor’s pilot study with small group of patients. A large scale long-term study is necessary. You will need funding to support that, either federal or private, particularly from pharma companies. Drug company money won’t come in until you get something interesting with federal money first or some charity foundations. However, if anyone in this field is seeking federal funding, they need to come up with a sound hypothesis of mechanism first. If no clear mechanism, you may get small seed founding, but no major one. That’s based on my personal experience. But in this particular case, antibiotic effect is not a viable mechanism since everyone, professional or non-professional, will be concerned about drug-resistant bacteria. That’s why you see both groups focused on immunomodulatory effect. However, before that, they will have to convince any reviewer that it’s not the antibiotic effect, or at least immunomodulatory effect plays a major role. It’s almost a mission impossible. Without detailed research, many doctors will not be willing to prescribe it since it will be off-label use and they will have to assume liability because of that.
As to vancomycin itself, one concerning issue, as mentioned at this forum a few time, is the vancomycin-resistant bacteria. Keep in mind that we’re not just talking about PSC patients, but also other patients or the community. This is not a minor issue since PSC patients will need to use it for decades, if it does work. I couldn’t think about any other condition that requires that kind of long-term use of strong antibiotics. A relatively minor issue is the potential renal toxicity of vancomycin. That’s a possible event considering the nature of UC. Again, long-term use could increase the risk.
There are lots of tricks in clinical research, including excuses. Tricks make those studies attractive to non-professionals, but won’t pass a solid peer-review process. We see that all the time.