In a recent MS Journal Club, my colleague Heather Mah presented an article about patient involvement in research. This then prompted the discussion about research bureaucracy, patient information sheets, and the standard of consent. Patient information sheets (PIS) are often long, text heavy documents that are impossible to understand. They are intended to provide all the information about a study to patients (risks/benefits/how your data is managed/how to withdraw, etc.) – but this isn’t the case. Researchers must complete these forms to meet regulator, legal and ethical requirements. Forms that were developed decades ago, have never been updated with strict sections and headings that can’t be altered, or they won’t be approved.
This raised a lot of questions: Does the information contained in a PIS matter? How many patients read (and understand) an entire PIS before consenting to research? How can we make PISs more understandable and accessible for patients? Does having a simple PIS co-produced with patients mean that people are more likely to join research studies? What does full consent look like, and is a degree of consent sufficient?
Does true consent exists – NO, it’s a matter of trust and novelty
Over the years, I have asked many pwMS and other individuals for their consent to participate in research studies. This has been for a wide range of studies with entirely different aims:
1. No benefit for the participant.
This type of study involves mere “databanking” or “biobanking”, and thus storing of blood or cerebrospinal fluid for scientific purposes. This could mean that the remainder of a blood sample which has been drawn based on clinical grounds would be used for research purposes. Other studies involved drawing blood or performing a lumbar puncture for the mere purpose of research. Along this line, some studies ask for permission to access your clinical data and brain MRI for research purposes (ie. comparing MRI features of people with similar characteristics).
2. Unclear benefit for the participant
Some studies involved testing a new drug in pwMS which had a similar mode of action than an already available drug. The trial comparing ofatumumab versus ocrelizumab is a good example. This study compared an established intravenous anti-CD20 infusion versus an untested, novel subcutaneous anti-CD20 formulation.
3. Clear benefit for the participant
An even smaller minority of the studies would involve potentially life-altering/extending interventions, such as new drugs for amyotrophic lateral sclerosis or ALS. This is a progressive neurological disease which is lethal in two to three years from now and for which no treatment – not even chemotherapy – exists.
In MS, the third category of studies is rare. These are the trials that would involve stem cell transplantation or remyelination/neuroprotective drugs. As we currently have more than ten disease-modifying treatments available, the majority of the studies will, however, have no or an uncertain benefit. Irrespective of category 1/2/3, the associated consent forms do always include a vast number of side effects related to study participation. A lumbar puncture for example might lead to post-puncture headache, and even more daunting a ‘sagging brain’. Anti-CD20 formulations lead to B cell depletion (= mode of action); increase susceptibility to infection, and reduce response to vaccination. Giving access to your data for research means they will end up in a database on an external hard drive outside of the hospital. Potentially, this would make your data more susceptible to data breaches.
Although none of these side effects are lethal; they do convey into small but existing safety risks that you would not be exposed to when not participating. Why do pwMS participate? Is this the equivalent of scientific altruism?
Although I truly believe in patient empowerment and pwMS taking better decisions when being fully informed, I do feel the most important factor weighing on the decision-making process is trust between clinician’s and their patients. Do pwMS believe you have their best interest at heart? If you as a clinician show evidence of good intentions and empathy (there’s no manual for this, but some clinicians are definitely better at it than others) and if you are convinced about the necessity to perform the research, side effects will inevitably get a silver lining.
Moreover, I honestly don’t think consent forms are currently drafted in a meaningful way for pwMS. How would unexperienced pwMS judge how awful a “progressive multifocal leukoencephalopathy” would be? In a very specialised setting like this, words are not always meaningful. You can only understand the impact of such a side effect when you happen to have seen someone suffering from it. This is by the way one of the main reasons why patient support groups are so valuable. Some pwMS are better at grasping risks than others, but understanding risks that you have not been exposed to yourself and that are not part of day-to-day logic (e.g. getting hurt when using a knife) is something very very difficult and prone to interpretation bias.
Based on my experience, obtaining true patient consent will always remain an illusion. No matter how accurate and accessible patient information sheets are, people most often do not read them before deciding or do not fully understand what they read. The likelihood of people participating will be influenced by the feeling of having had the possibility to be fully informed and a mutual appreciation between the clinician and the consentee. Nonetheless, this does not mean we should not try to inform our pwMS with the best and most accurate information. Offering the information is a question of moral duty.
Have you ever been asked for consent? And which factors were decisive in this process?
Disclaimer: Please note that the opinions expressed here are those of dr. Ide Smets and do not necessarily reflect the position of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust.