While we need a cure that’s specific to the biochemistry of individual rare disorders, there’s still a lot we can learn from the other rare bone disorders and their patient advocacy work. I’m particularly impressed by a current project by the Osteogenesis Imperfecta Federation Europe to better understand bone pain. OI is a rare bone disorder with a very different cause and treatment regimen from the chronic hypophosphatemias, but the lived experience for patients is very similar. Like us, they deal with frequent fractures and serious bone pain.
OIFE is preparing for a conference in June on “Balancing Life with OI,” and I believe a significant focus will be on coping with pain. I’ll be looking forward to the report that comes out of that conference, and they’re already given me food for thought, by way of a quote from an expert in pain:
Pain INTERFERENCE is the key. Does the pain interfere with your social life, work, sleep etc? Problem is that EMA/FDA always requires us to include pain intensity to measure efficacy of a drug/treatment. So pain scales are necessary in clinical trials, but not useful in clinic.
Quote is from Audun Steubhoug.
It’s such a great insight, one I hadn’t thought about in quite those terms. I think we need to take it a step further and find a way to capture/define/record pain interference, not just in the clinic, but also in clinical trials, perhaps in addition to the pain intensity scores, rather than replacing them completely. It might also be useful to have correlation work, where, alongside the pain intensity scale, there’s a series of questions intended to help better understand what pain a patient thinks qualifies for different pain levels. Just to give a silly example, but one person who’s highly sensitive to pain might consider a paper cut to be an eight (upper tier of the pain scale), while an XLHer would likely rate it a zero or one (except of course outside the clinic, where we might claim we were dying of the pain, so we could get some sympathy or a treat!).
When I was in the burosumab trials, the first published data about its effect on pain levels (based on the pain intensity data). if I remember correctly, showed only a small, and possibly not statistically significant improvement in pain levels for patients when compared to placebo. But what the data didn’t capture was what I experienced myself: a huge increase in my ability to pursue daily activities before the pain stopped me.
It’s like I had a pain threshold, beneath which I didn’t even consciously notice the pain, which was just background noise. That threshold then was captured in the data for the clinical trial while I was on placebo, in the daily pain scale reports. So I would go about my day until I hit that threshold, and then I’d have to pretty much give up doing anything for the rest of the day (or pay the price the next day if I pushed on). While on placebo (and therefore not on any real treatment), I hit that threshold after doing very little. Once I was on the treatment, I still hit that threshold, so my reported average pain intensity level remained the same, but I hit that barrier only after doing considerably more activity and being much more productive.
The problem with that data is that there’s no way to add a note to the surveys I completed that would explain how much more active I’d been while my pain levels remained the same. That’s a problem for all of pain research — there are standardized methods/tools, which have been proven to be useful, and researchers can’t change them without first proving that the changes are reliable. So the issue with the clinical trial isn’t that the researchers used the wrong tool, but that there is no tool that would capture the effects of pain on activity levels and vice versa.
I vividly remember reporting a slight increase in pain one week, when I’d been traveling (always a source of increased pain). Before treatment, I would have also had that increase in pain, probably to a higher level than I experienced, and then would have been bedridden for a week afterward. With treatment, I still hurt from the activity, but I bounced back after a good night’s sleep, without any ongoing bedrest. So the effect on my daily activity was much, much less after treatment than before, but I had no way to include that in the data, no way to essentially put an asterisk on my intensity scale responses when something out of the ordinary increased my pain level. There just wasn’t any way to capture what I wanted to add: “My pain intensity went up on these days, because I was running around like a crazy person, which I couldn’t have done without being on the treatment.”
I’ve heard similar stories about increased activity with the same/reduced pain intensity from other patients, both during the clinical trials and then later, after burosumab became commercially available. I don’t know what these patients reported for pain intensity levels, but their activity levels increased significantly, and as noted, the standardized questionnaires about pain levels have no room for mentioning factors that might have affected those levels in a given time period. Kids who could barely drag themselves home at the end of the basic school day before treatment were enrolling in gymnastics and other after-school activities after treatment. Adults who’d been couch potatoes due to pain were taking daily walks or enrolling in a bowling league for the first time ever in middle age. But there’s no way to capture those factors in the standard/validated pain level reports.
I don’t have the scientific expertise to design a good solution to this problem, but if pain relief is a critical endpoint for a clinical trial, we need to find a way to include both the pain level AND simultaneously the daily activity level that produced that pain. Otherwise, we’re not getting the full picture of whether a given treatment has a meaningful impact on that endpoint. Instead, as I believe was the case with the burosumab clinical trial, the pain-related benefits of the treatment are significantly under-appreciated.
It might be as simple as asking both the standard pain-intensity questions and, simultaneously, some recognized questions about daily activity levels, like those in the International Physical Activity Questionnaire. Other factors can also affect pain intensity, especially sleep quality (I know I can handle more pain when I’m well-rested than when I’m tired as well as in pain), so information about factors like sleep and stress might need to be included too to get the full picture. Possibly also something about traumatic events; the loss of a job or a family member or pet could make patients more sensitive to pain, so knowing that there were (or were not) additional factors could be useful.
The bottom line is that there are many reasons why reviewing agencies like the FDA or the European Medicines Agency love the 10-point pain scale, and why patients loathe it so much. (Can’t miss this opportunity link to my preferred pain scale by artist Allie Brosh.) The scale has a legitimate role in research, but it’s incumbent on patient advocates to point out ways to improve the understanding of pain in both the clinician’s office and clinical trials. Until we have more comprehensive research into the pain that comes with chronic hypophosphatemia, individual patients will need to be vocal about their pain, and how it’s not fully captured in existing research or existing tools.
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Please note that the author is a well-read patient, not a doctor, and is not offering medical or legal advice.
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