Research Involving Human Subjects: Is Nova Scotia Ready?

Few scientific endeavours are so wrought with controversy, still veiled in mystery, misunderstood and stigmatized, despite the abundance of publicly available information and long history of regulation. I am talking about clinical trials; testing safety, efficacy, superiority of new drugs, combination of drugs, or devices, on human subjects. 

This is also a space filled with grey zones which I will try to illuminate from purpose, profitability, ethical conduct, to the end result in a lot (albeit not all) cases: a new drug or device hits the market, its inventor gains years of intellectual property rights, massive profits, and the participant is left with their data possibly transferred, traded and used for purposes other than the clinical trial itself. One’s insurability may also be affected since insurance companies, by way of access to Medical Information Bureau-MIB, have access to some of your health information as it pertains to insurability. 

Clinical trial participants get access to the highest quality care with regular oversight and no wait times, much like private health care which many oppose vehemently. For the rest of us, some do not even have primary health care providers and while carefully taking our vitamins, attending early detection exams and tests, we wonder if medical resources at Nova Scotia Health by sheer engagement in research, become unavailable or less available for delivery of “regular” health care.

All the clinical trial-associated risks are clearly outlined in the Informed Consent Form (or ICF, for short). Signing an ICF is a necessary step for an individual to gain enrollment in a clinical trial. These documents are very long, up to 20 pages, and while absolutely everything known about the risks of the study, privacy, data protection, is disclosed, there are unknowns about the future data use, sort of, hiding in plain sight. Attention span these days is very short. For me, going through a 20-page document certainly requires mental preparation.

Let us take a step back to the place where we left off in the last blog post: Your Health NS app, as the portal, or a springboard to clinical research involving human subjects in Nova Scotia. 

The looming question is: Are Nova Scotians ready and medically literate enough (or eager to learn), to take advantage of this initiative and understand its pros and cons?

If you launch the app and check out what is listed under “Services”, you will find a menu of 12 nicely laid out options. Among them, listed as eighth in a row, is “Research and Clinical Trials”. Not easily discoverable, but once you are there, a wealth of information awaits! You will have landed into a new space entitled “Nova Studies Connect”. This is an exciting feature and initiative that Nova Scotia Health launched to connect patients across Nova Scotia with the research community and ongoing and upcoming clinical trials and research initiatives. This is essentially a database that you can search using a disease or a condition (eg. arthritis), as a search term. The search will return active and upcoming studies involving patients suffering from arthritis, along with a lay person’s study description.

Once you access Nova Studies Connect, you can learn more about clinical studies in general (there is a section about that which is well-written), and you can also click on “Join Nova Studies Connect”, a tab that takes you to an online consent form which, when signed electronically, means you have given permission to NSH to enter your full name, MSI health card number, date of birth, postal code, gender, and your medical condition(s), into a database of patients who have expressed consent to be contacted for research in the future.  This approach is fully compliant with the Personal Health Information Act, or PHIA. 

What this means in reality, is that if you entered “arthritis” as your medical condition, a member of the research team may call or email you in the future, to invite your participation in a research or clinical trial where arthritis is being treated. You may also withdraw your consent when you get that call, or anytime you change your mind (bottom of the page features NS Health Privacy statement which explains, in plain language, your rights and how to withdraw consent and/or get more information. I am quite impressed by how nimble and elegant this solution is, and especially how well-worded and clear Nova Studies Connect content is. Thumbs up for that one!

To the nitty-gritty now: what is clinical research and what may be in it for you in this province?

For simplicity’s sake, let’s just say that in clinical research/clinical trials, you, as a participant, will receive the Cadillac of care: no wait times for imaging, diagnostic tests, prompt medical attention if you experience what is referred to as an Adverse Event (AE). This highlights the sad reality that in Nova Scotia with a deeply challenged health care system (shortage of medical personnel, equipment, IT infrastructure), your best bet to receive top-notch care, may be enrolling in a clinical trial. 

Clinical trials are performed to demonstrate safety and efficacy of new treatments, or compare existing treatments with new ones (phase I, II, and III trials), or simply to observe effects of a drug or treatment AFTER it has received marketing authorization by FDA or Health Canada (post-market surveillance or phase IV). In phases I (healthy individuals), II, and III (patients), the sponsoring pharma companies are paying the doctors, institutions, and sometimes participants, for their new drug (or device) testing. In phase IV (post-marketing surveillance), the patent rights would have kicked in as health authorities worldwide have approved the drug for widespread use. The benefit of post marketing surveillance is that it can collect data on a much larger number of patients and possibly discover avenues for their off-label use. An example of that is minoxidil (Rogain), an antihypertensive medication, better known for its off-label use to treat alopecia (hair loss).

Clinical trials are exceptionally tightly regulated at so many levels. Worldwide ICH GCP (International Counsel for Harmonization, Good Clinical Practice ): https://database.ich.org/sites/default/files/ICH_E6%28R3%29_DraftGuideline_2023_0519.pdf

In Canada, the guidelines are outlined in the so called Tri-Council Policy-2 (2022) https://ethics.gc.ca/eng/tcps2-eptc2_2022_chapter11-chapitre11.html

While TCPS-2 provides some overarching principles, Health Canada nevertheless reviews the vast majority of interventional clinical trials to be undertaken anywhere in this country, including Nova Scotia. 

Then, at the provincial level, various privacy and personal information protection regulations kick in, as is the cases with PHIA in Nova Scotia: https://novascotia.ca/dhw/phia/PHIA-legislation.asp

If that is not enough, there is one last checkpoint at the institution/clinic/hospital level: Research Ethics Board or REB that reviews each clinical trial with a lens of safety of human participants. REBs are made up of at least seven members (more commonly, over 10), and the required composition is medical professionals, lay persons, legal experts, and bioethics professionals. 

After all this, you may conclude  research participants are well-informed (through the informed consent process), well-protected (after so many levels of safety, ethics, and privacy reviews), well looked after before, during and after the clinical trial (as a clinical research participant, you are seen by the nurse or the physician in regular intervals, without hassle or wait times). 

Add to that as a research participant you are told you are helping advance treatment for particular diseases and conditions, even if the treatment you are undergoing may not help you directly (especially if you are assigned to the placebo arm).

All positives, right? Not necessarily.

Acknowledging generalization here (not all clinical trials are funded and sponsored by pharmaceutical companies), it is important to note that those pharma-sponsored trials reach Nova Scotia in their phase II or III (involving dozens to thousands of participants worldwide). They are extremely well funded, covering costs of every single exam, diagnostic imaging, lab test you will need in the course of treatment (and that are otherwise unavailable to general public). It is ironic how vocal opponents of private health care can be, yet clinical trials are as close as it comes to private health care access. One of the newer trends is not just reimbursing participants for their travel expenses, but also compensating/paying for their time and effort of participation. 

As pharmaceutical company-sponsored research participant, you will receive the best care possible but you will have also donated your data and health care findings (often times these days, genetic test results also), for the purposes of future research, development of new drugs and treatments. The wording around what happens with your health care data is oh, so carefully wrapped in the vague wording of the ICF, hiding in plain sight that you are basically fueling profits for the study sponsor now and in the future as your data may eventually be sold, traded, and used for a variety of purposes, even if remains anonymous. Anonymity of data is a whole other can of worms in the world of clinical trial globalization, and cloud storage. 

While a clinical trial participant, small as he/she is, is fueling pharma companies’ profits and stock prices, you ought to remember that if the tested treatment is deemed to be safe, effective, and/or better than the current standard of care, that same pharma company will now release the new drug or treatment into the market and your government will be paying big bucks to ensure its accessibility and full or partial coverage for general public, or a niche patient population. 

In case you liked the sound of “private health care” parallel I draw with clinical trials and want to jump on board: think again…An average phase III clinical trial will enroll anywhere between 800-10,000 participants worldwide. Of those numbers, Canada usually gets a small pie slice (several patients to several dozen patients). Finally, what filters as allocation to Nova Scotia may end up being fewer than 10 patients, so very few of those potentially eligible or interested may get enrolled; hardly a viable alternative or addition to public health care.

This is offset by the fact that there are many research studies and clinical trials taking place in Nova Scotia and every single one is listed in Nova Studies Connect (searchable by key word or disease name in the nifty feature within YHNS).

Most clinical trials include a period called long-term-follow-up (LTFU), that lasts up to 2 years, sometimes longer. Some basic information will be collected about your health during this period, however, the intense scrutiny and rigor of active phase of a clinical trial will be long gone and you will be left to your own devices or if you are lucky to have one, in the hands of your primary care provider.

It is important to stress yet again that not all medical research is in the category of interventional pharmaceutical industry sponsored trials. Many bright minds in the research community apply for government and institutional grants and perform their own studies, some of which are observational (collecting data from a subset of patients, such as effect of meditation on stress hormone levels). Sometimes these observational studies encompassing very large numbers of people, are referred to as real-world evidence (or RWE). While they will not contribute immediately to anyone’s profit margin, data is gold in this day and age, and many companies south of the border are rallying troops to collect, analyze, and make the best use of our health data. 

To support (willingly or unknowingly), those big dataset exploitation possibilities, we are seeing several trends in clinical research: diversity, equitable access, decentralization, personalized medicine (using genetic information to provide targeted treatments), and patient monetary compensation. There are both efforts and funds behind reaching across all geographic and demographic spaces everywhere in North America, including Nova Scotia (outreach to Indigenous, black, Asian, culturally diverse populations). Technology is now favouring ability to complete some of the clinical research assessments remotely, wherever the patient lives, via a tablet, smart phone, or laptop, with a need to come to a clinic only for specialized testing. There is a global push for including and involving more people and more diverse populations in clinical research. This may sound like, and may indeed be, a truly philanthropic and basic human-right rooted approach, or it may be the lead into an unprecedented data collection and mining wave for purposes we may not be able to predict. Personally, I am most concerned about that which I don’t know I don’t know.

These wide swaths of data can point to behavioural trends, to demographic and genetic correlation with certain diseases. With better understanding of the health care service users (including prescription drug users), of course, the inventors and manufacturers can better devise new or “new” treatments to address what is usually dubbed as “unmet need”.  

Birth and death have both been medicalized for a long time in North America, and as such, beginning and end of life spaces filled with prescription medications and chemicals, to help cope with perfectly natural processes. More recent additions to this space include menopause and obesity which are now talked about as complex medical conditions that (presumably) require complex treatment approach (aka multiple prescription drug solutions). Same goes for mushrooming of treatment options for mental health and emotional disturbances and disorders, leaving less and less space for personal, empowered intervention, or prevention.

I feel that space should be maintained or carved out for both- the realm of prevention and self-intervention, as well as medical treatment. The former is sadly being eradicated even though we live in a province where the current state of health care makes prevention our best and safest bet.