Earlier today I had a follow-up appointment with my treating physician, at the university-hospital pain management unit (PMU) at which I receive treatment for CRPS. Complex Regional Pain Syndrome is an autoimmune and neuro-inflammatory disease, which carries a long and diverse list of symptoms.
Any one patient might experience some of these symptoms, while another would report a different set; all to varying degrees or levels of severity. It’s often said that each CRPS patient presents differently; each affected individual presents with a unique set of clinical signs and symptoms.
Adding to this complexity is the fact that CRPS patients also respond differently to treatments. A medication or intervention which shows some benefit for one patient with this disease may make no difference to another. This makes the condition very frustrating to treat, for both clinicians and patients.
From a patient perspective, it can start to feel as though every proposed treatment is ‘hit or miss’. Even though something was helpful for other patients with similar symptoms, that doesn’t necessarily mean that it would provide any benefit in your own case. Here’s a good example of how physicians explain this ‘hit or miss’ approach:
Treatment for CRPS is most effective when applied in a cohesive multidisciplinary venue.
The treating physician should be aggressive with medical therapies, systematically experimenting with opportunistic pharmaceutical approaches”(1).
Although each patient with CRPS may have different sets of symptoms, the most frequent of these is neuropathic (nerve) pain. This tends to include allodynia, an extreme sensitivity of the skin. This can make it difficult to tolerate the touch of fabric on one’s skin; even the sensation of a breeze on the skin can trigger intense and severe pain with allodynia.
So when my physician mentioned that this university and hospital would soon be conducting a clinical trial, for neuropathic pain, I was intrigued. Because my doctor is involved in this research project, though, it could be ethically problematic for him to discuss it with me directly.
I should add at this point that my field is biomedical ethics, also called bioethics. That’s why the name of this blog is BioethiCanada; I started blogging back in 2007 about bioethics, and then added the CRPS section soon after my diagnosis in 2016.
Why could it be viewed as an ethical issue, if my doctor were to ask me to participate in this clinical trial? Because studies have shown that some patients don’t feel comfortable saying “no” when their clinician asks them to participate in a research project.
If my doctor were to ask me himself, that could be seen as an inadvertent form of coercion; of – even unintentionally – forcing someone to agree to do something that they normally wouldn’t do.
To prevent this type of situation, my physician asked whether it would be okay for him to give my phone number to one of the research coordinators for this clinical trial.
The coordinator would explain the research project to me, and answer my questions. And then I’d decide whether or not the trial interested me. And, of course, I could discuss it with loved ones or with another doctor; like my family physician.
As you’ve probably guessed, I said yes! I spent years managing a research ethics board (REB) – called an institutional/independent review board (IRB) in the United States – so had always hoped to be able to participate in a clinical trial someday… Although I’d hoped it would be as a health volunteer, rather than as a patient ‘-)
Patient participation in research is especially important for CRPS, because:
Due to a lack of information on the pathophysiology of CRPS and the similar absence of consistent objective diagnostic criteria, clinical trials that demonstrate effective therapies are difficult to perform. Therefore, only a few evidence-based treatment regimens are currently available.”(1)
As I wait for their call, to discuss this research project, I thought it’d be fun to blog about some of the technical terms involved in this clinical trial. The language of clinical – medical – research can seem intimidating, to anyone who hasn’t worked in this field.
Let’s start with an easy term. This research project is ‘interventional’ rather than ‘observational’. In an observational study, nothing changes other than that data (information) is collected about a current situation. Imagine someone who’s already taking a medication for a disease, who’s then asked to complete a questionnaire – about this disease – once a year for 10 years.
That would be observational research, for example to determine whether there’s a long-term improvement in symptoms for patients using this medication. Using the same example, an interventional study could be if a medication was added or modified for that patient; something would be changed in the research participant’s treatment.
We’ll look at another familiar term next. This particular clinical trial will involve an ‘experimental’ study product. In this case, the study product will be a mix of medications; it could also be a medical device, or even a surgical procedure. The study product refers to whatever it is that will be tested in the experiment.
Experimental can also signify that the product hasn’t yet been approved for sale in Canada – or that it hasn’t been approved for this specific use. The experimental product for this study is actually a combination of two medications that have already been – individually – approved by Health Canada.
The experimental aspect is their combination – or compounding – into one topical product; a liquid lotion-type product, to be applied to the skin. In this project, 2 different study products will be used by each participant; each a combination of ingredients.
One study product contains the lotion with the two active medications, and the other is the same liquid but without the active medications. This is called a placebo; it looks, feels, and even smells like the active ingredients (e.g. medications) – but it doesn’t contain the active ingredients. That makes this a ‘placebo-controlled’ clinical trial.
It’s also a ‘crossover’ trial, because during this research project, I would be applying both study products to my skin – where I have allodynia. First I’d receive either the active or placebo study product for several weeks, then the other product for the next several weeks.
So I would cross over from one study product to the other, as part of this clinical trial. If I’m accepted as a research participant for this clinical trial, there would also be a ‘washout week’ between the first few weeks and the last few weeks of the study; in the middle of the research period, I won’t use either product for a week.
Are you with me so far? Ready for a few more clinical – medical – research terms? Let’s continue!
This will also be a ‘triple-blinded’ study. That means that none of the three different groups of people involved in the research will know which study product is given to each participant – or in which order.
As a patient-participant, I won’t know whether I’ll receive the active product for first 2 weeks or the last 2 weeks. And neither will the members of the research team (the study coordinators, and principal investigator), nor the assessor(s) who will analyse the images and other data collected as part of the study.
Research is often ‘blinded’ in this way, to prevent the researchers from inadvertently influencing the study results. Let’s look at a hypothetical or imaginary example.
If a study coordinator knew that I’d been using the active study product, they might ask a surprised “Are you sure?” if I told them that I hadn’t felt any difference in my pain level.
And that surprise, on their part, could prompt me to change or reconsider my response… to subconsciously try to conform to what I felt was expected of me as a research participant. That could influence how I respond to other questions, even in a very subtle way.
And that could skew the research data, and end up showing a small benefit when there really wasn’t one. Or vice versa.
Another term you might have heard is ‘randomized’. To ensure that the patients and research team can’t effectively guess which study product will be used first, the participants don’t all receive the same product during the same weeks of the clinical trial.
The study product will be randomly assigned, like flipping a coin to decide which team will start first in a football game or who’ll start first in a board game.
I mentioned earlier that it’s not certain whether I’ll be accepted into this clinical trial. That’s because most research includes two different lists; 1) inclusion criteria, and 2) exclusion criteria.
To be eligible to participate in this research project, I will have to meet all of the inclusion criteria, and not have (or meet) any of the exclusion criteria. Again, this sounds more complicated that it is.
Let’s look at another hypothetical example, this time for a clinical trial involving an allergy product. One of the inclusion criteria could be to have the specific type of allergy being studied. So the researchers might ask all potential participants to have an allergy test, to confirm that they have the allergy they want to study.
One of the exclusion criteria might be taking a certain medication; one that’s similar to the study product. Because then the research team wouldn’t be able to tell whether the study product was helpful for the allergy, or whether it was the product that the participant was already taking.
Cross your fingers for me; that I’ll be eligible for this research project, as I’d really like to be able to participate in my first-ever clinical trial. It would be an honour for me to be able to contribute to the body of knowledge on CRPS, to possibly help other patients with this life-changing disease by bridging gaps in its scientific understanding:
A problem of multi-faceted pathophysiology is that a “one fits all”-treatment for CRPS will probably never be available.
Another big problem with CRPS therapy is that high-quality randomized controlled multicentre trials (RCTs) are missing.”(2)
In the meantime, let’s wrap this all up. The clinical trial in which I hope to participate is described as an ‘interventional randomized triple-blind crossover’ clinical trial. As I said, it seems much more complicated when presented that way!
I hope now you’re able to look at these types of research descriptions with a better understanding of what they mean. As always, thanks for reading and feel free to reach out via Instagram or Twitter if you’d like more information on this topic!
References
(1) Complex Regional Pain Syndromes Treatment and Management. Gaurav Gupta and Stephen A Berman. Editor: Stephen A Berman. Medscape: Drugs and Diseases; Neurology. Updated: 10 Jun 2018. Online. Accessed 25 Oct 2018.
https://emedicine.medscape.com/article/1145318-treatment#d5 (Membership
may be required to access the full-length article.)
(1) Complex regional pain syndrome-up-to-date. Frank Birklein, Violeta Dimova. PAIN Reports; PAIN Clinical Updates. Nov/Dec 2017. Volume 2, Issue 6, page e624. doi: 10.1097/PR9.0000000000000624. Online. Accessed 01 Nov 2018.
https://journals.lww.com/painrpts/Fulltext/2017/12000/Complex_regional_pain_syndrome_up_to_date.8.aspx?WT.mc_id=HPxADx20100319xMP