Bear with me on this, I've only just invented this thought experiment, so it's quite likely to go pear shaped.
A new drug is invented to treat ME/CFS. The people who invented it are sure it will work, and they have a biological rationale for the drug which they are proud of and have written papers about even before testing it on anyone. They are pinning their status and careeers on this drug.
They design a clinical trial. Unfortunately it can't be blinded like most drug trials because every time someone takes a dose their big toe turns green for half an hour.
They set up a pilot study. It's designed to last for 6 weeks. They explain the rationale to the patients and tell them it's a great new invention and they are lucky to be given the drug for free for 6 weeks, as there's a good chance if they follow the dosing regime of two pills a day carefully they will recover.
6 weeks later, on average the 10 patients questionnaire results show that they are a bit less fatigued and are able to walk a little further. The researchers publish this result, with the conclusion that they are sure taking the drug for longer will lead to even better results. They are confident they have found the cure for ME/CFS.
So their government medical funding agencies give them lots of money to set up a bigger trial, and design it to last for 6 months this time, and they have a control group who are on the waiting list for the treatment.
After about 6 weeks the results look mildly promising again, and they are confident patients will continue to improve.
After 3 months some patients are complaining they are having more episodes of PEM and taking longer to recover from them. The researchers tell the patients not to worry, it's just a bit of a glitch, leave off the pills for a day then build up again to the full dose. By 4 months some patients are quietly cutting back on their pills, trying half doses without daring to tell the researchers, more and more are hitting the buffers with worse crashes. The researchers tell them they must be doing something wrong. Perhaps they are eating the wrong food, or mixing the pills with other medications. It can't be the pills stopping working. So most of the patients persevere, but a few are dropping out.
By 6 months, those patients who have stuck rigidly to the full dose regime are feeling a whole lot worse, but most have quietly cut right back on their pills and are not so badly affected. No better than they were before the trial, but not much worse either. They are glad the trial is over, and worry they must have done something wrong, so they fill in the questionniares saying they are a bit better. Those who are much worse from following the regime rigidly aren't well enough to fill in the final questionnaires, so their results are never recorded.
The researchers look at the results. They realise they need to make some adjustments to their paper on the study in order to be able to claim success, so they fiddle around with the figures and find by using a different way of calculating the results of the fatigue questionnaire, and adjusting downwards their limits for 'success' they can still claim the treatment works.
They publish a paper with great public fanfare reporting they have the cure for ME/CFS. All patients need is two of their 'green toe' pills a day. They report no adverse effects, and don't include any data on patient compliance with the dosage regime.
A couple of years after the release of the drug, patient organisations do a large survey of patients experiences with the drug and find that the vast majority report an initial period of a few weeks of mild improvement followed by serious deterioration. And even worse, those who stuck to the drug regime for more than 3 months are still very sick a year or more after stopping taking it.
Cochrane has written a review supporting the use of the drug, and now refuses to withdraw it, saying there is not clinical trial evidence of harm.
End of thought experiment.
GrEen Toes doesn't work and harms patients.
A new drug is invented to treat ME/CFS. The people who invented it are sure it will work, and they have a biological rationale for the drug which they are proud of and have written papers about even before testing it on anyone. They are pinning their status and careeers on this drug.
They design a clinical trial. Unfortunately it can't be blinded like most drug trials because every time someone takes a dose their big toe turns green for half an hour.
They set up a pilot study. It's designed to last for 6 weeks. They explain the rationale to the patients and tell them it's a great new invention and they are lucky to be given the drug for free for 6 weeks, as there's a good chance if they follow the dosing regime of two pills a day carefully they will recover.
6 weeks later, on average the 10 patients questionnaire results show that they are a bit less fatigued and are able to walk a little further. The researchers publish this result, with the conclusion that they are sure taking the drug for longer will lead to even better results. They are confident they have found the cure for ME/CFS.
So their government medical funding agencies give them lots of money to set up a bigger trial, and design it to last for 6 months this time, and they have a control group who are on the waiting list for the treatment.
After about 6 weeks the results look mildly promising again, and they are confident patients will continue to improve.
After 3 months some patients are complaining they are having more episodes of PEM and taking longer to recover from them. The researchers tell the patients not to worry, it's just a bit of a glitch, leave off the pills for a day then build up again to the full dose. By 4 months some patients are quietly cutting back on their pills, trying half doses without daring to tell the researchers, more and more are hitting the buffers with worse crashes. The researchers tell them they must be doing something wrong. Perhaps they are eating the wrong food, or mixing the pills with other medications. It can't be the pills stopping working. So most of the patients persevere, but a few are dropping out.
By 6 months, those patients who have stuck rigidly to the full dose regime are feeling a whole lot worse, but most have quietly cut right back on their pills and are not so badly affected. No better than they were before the trial, but not much worse either. They are glad the trial is over, and worry they must have done something wrong, so they fill in the questionniares saying they are a bit better. Those who are much worse from following the regime rigidly aren't well enough to fill in the final questionnaires, so their results are never recorded.
The researchers look at the results. They realise they need to make some adjustments to their paper on the study in order to be able to claim success, so they fiddle around with the figures and find by using a different way of calculating the results of the fatigue questionnaire, and adjusting downwards their limits for 'success' they can still claim the treatment works.
They publish a paper with great public fanfare reporting they have the cure for ME/CFS. All patients need is two of their 'green toe' pills a day. They report no adverse effects, and don't include any data on patient compliance with the dosage regime.
A couple of years after the release of the drug, patient organisations do a large survey of patients experiences with the drug and find that the vast majority report an initial period of a few weeks of mild improvement followed by serious deterioration. And even worse, those who stuck to the drug regime for more than 3 months are still very sick a year or more after stopping taking it.
Cochrane has written a review supporting the use of the drug, and now refuses to withdraw it, saying there is not clinical trial evidence of harm.
End of thought experiment.
GrEen Toes doesn't work and harms patients.
