Clinical trials basics for patients
Over a year ago, I found out that a friend of mine had been diagnosed with a very rare form of cancer that most frequently affects the hands and forearms, termed epithelioid sarcoma. Not the rarest cancer in the world, but with an incidence rate of 0.4 case per million individuals per year, this cancer has been difficult to study, with no established optimal therapeutic strategy, and causes suffering due to poor treatment outcomes.
I wanted to do whatever I could for my friend, and set out on a research course for this type of cancer. My first task was to look at the genetics driving epithelioid sarcomas, and through discussions with number of experts in the field, I was connected to a coordinator of a unique phase II clinical trial just taking place which was related to the condition afflicting my friend. I thought it was an amazing stroke of luck for my friend! The medical study was unique in that it was the first study ever conducted on a drug that was to modulate the epigenetic regulation of a gene.
What does that even mean? Genes can be regulated to the degree in which they will be used by the cells through a variety of means. One such method is to extent the DNA that is actually accessible for use, and this can be achieved by the chemical modification of the DNA itself (or epigenetic regulation). It is like adding beacons of information that tell the cell, “hey, open this section up”, or “let’s move on”. This drug was actually going to help regulate such DNA access to a gene of interest, as opposed to targeting the product of the gene itself. And that has never been tried before.
But my friend backed out, deciding that they would not be interested in pursuing that option, and it was not worth taking the chance. I could tell my friend was prejudiced against the idea of undergoing a clinical trial, and seemed afraid of it, perhaps thinking that it would be some highly experimental process with potentially unreasonable risks. Or perhaps, even more cynically, that people were being used as pawns in pursuit of profit. I spent a long time trying to clarify as best as I could the information behind the trial. While in the end I completely respected my friends final choice, never doubting that it was a the right one for them, at the time I also couldn’t help but feel that I had not been good enough in explaining the details, and wished I had some additional resources to provide. The doubt was with me, not with my friend’s rationality.
Now I have such a resource: Clara Health, which is a one stop shop for patients interested in learning more about, searching, and enrolling in clinical trials. Clarahealth.com is a platform connecting patients to clinical trials and supporting them throughout the process. When I had the chance to become one of their many advocates and join the Breakthrough Crew, I did not hesitate for a moment!
Clinical trials are research studies where volunteers help researchers look at new ways to prevent, detect, or treat conditions.
But while experimental in nature, the proposed treatments being tested have already gone through a series of lengthy and thorough research processes, typically at enormous risk and cost to the pharmaceutical industries, to offer the medication or devices for trials in humans. This likely would have already included work with animal models and human cell lines or tissues to examine toxicity and outcomes. By the time the clinical trials commence on humans, there is already an accumulation of evidence towards the potential success in humans. The trials are to confirm the efficacy and safety of the proposed treatment, and are typically done in multiple phases on continuously larger cohorts of patients to properly validate all of the findings. After all, it has to be remembered, clinical trials are the very last stage before a tested treatment is approved for the market and for use by everyone else. It is the final countdown of a very long medical research journey.
Furthermore, the tested treatment is often expected to deliver results at a higher quality of standard than whatever existing methods might otherwise be available. Whether that is greater efficacy, reduced level of toxicity and side effects, or faster results.
On top of that, all such trials are done under the very close scrutiny and oversight of each participant, usually far surpassing what would be expected in standard care. Obviously the goal is to ensure the utmost safety to participants of clinical trials, and the careful monitoring of outcomes is paramount to maintaining that safety. If side effects in any participant are noted, they are to be communicated to the remainder of the participants in order to constantly ensure informed consent. And each participant always has the option to withdraw at any time of their choosing.
So while clinical trials can conjure up a sense of fear and anxiety, it is more like a white-glove treatment experience for the participants that future users of the same treatment - once it is available on the market - will never experience.
In many instances, these experimental drug treatments might be the only avenue for some people to be able to battle the disease, or ever gain access to such advanced methods of treatment. Due to the rigorousness of the research process, all of the different phases of clinical trials where different groups of participants are treated can last more than 10 years alone, and sometimes regulatory hurdles can delay the public availability of such ground-breaking treatments even further. Thus, patients in a clinical trial can gain access to very important medication much earlier than they otherwise could have.
The medications being tested are becoming increasingly sophisticated and precise, thanks to the ever-greater understanding of the molecular causes driving the disease. With the advent of genome sequencing, patients now have the added advantage of obtaining a detailed molecular DNA profile that can significantly aid in clinical trial selection. This is particularly beneficial for cancers which arise due to wide array of different DNA mutations, and would have been the case for my friend, who would have to undergo the sequencing of a cancer biopsy.
That is not to say participation in clinical trials is without risks. After all, any clinical trial, especially those for a completely new type of medication, could always result in unknown or unsuspected side effects. Ultimately, one has to make a personal decision for themselves if the benefits outweigh the potential risks, and in the case of my friend, the perceived risks were not worth it. Even for the treatment of a potentially very dangerous condition. However, the risks are often the primary focus, and they should be, but they do have to be judiciously compared to potential benefits as well. Consequently clinical trials, and the benefits they can offer, are often poorly understood by the public.
So I wish I had known about Clara Health previously, in order to see if it could have alleviated any worries for my friend. It is not just a tool to find clinical trials for your particular issue, it also explains many concepts of medical trials in great depth, making it a great educational tool as well.
I am all about education, so I find that if you visit the Clara website and read through the the home page, the next best step is to go to the Clara help section, to get a good sense of what clinical trials are all about. It is set up into convenient guides that follow the patient journey through a trial, from the considerations prior to starting, gaining acceptance into the trial study, what happens during the medical trial, and the expectations post-trial. I think everything else afterwards will feel less daunting, be it searching for trials for one’s own condition of interest, or setting up a profile account.
A profile account? Yes, you can set up your individualized information board that essentially is your way of letting the Clara team know how best they can help you get to the trial that will benefit you the most. This is obviously the greatest advantage of this organization: that there are people knowledgeable in the process that will spend their time to help you, saving either you or your doctor that ordeal.
The search engine for clinical trials is beautifully designed. Perhaps I am not the best judge as I am familiar to some degree with clinical trials already, but in comparing a trial description between the Clara website and that of the official clinical trials website, which is run by the National Institute of Health, there is a world of difference for the benefit of a layperson. And if you have already set up an account with Clara, you can save all the trials that are of interest to you for easy tracking and future access.
My only problem with Clara, which in my opinion is a big oversight, is that the clinical study identification numbers are not listed. Each clinical trial has its own identification number that allows for an easy search for a particular trial on the https://clinicaltrials.gov/ website, and these ID numbers are often used, so they are handy to have. In addition, if a patient finds a trial of interest on the Clara website, the primary care physician of the patient might wish to study https://clinicaltrials.gov/ for the detailed trial information, as they might already be very familiar with this resource. Even a savvy patient, once becoming quite familiar with the outlay of Clara trial finder site, might be able to tackle the site provided by the NIH.
Another important resource for potential participants is the handy list of questions for clinical trial coordinators. These are all good questions to think about anyway before considering a clinical trial. I hope that in future reiterations of Clara’s trial finder, many of these questions will actually be answered on the website (not all of them can be). This is because that is a long list of questions, and it can be very intimidating to talk to a clinical trial coordinator. It was even difficult for me when seeking solutions for my friend, and I am someone with a scientific background that can traverse through much of the lingo that might be lost on others. These are very busy individuals, and while my experience had been encountering nothing but kindness, there can be that sense of guilt of taking up their precious time to educate me about trial details. Should I have already known these answers from other sources?
But ultimately it has to be remembered that clinical trials often have a hard time recruiting patients. The majority of patients that could be eligible for a trial will never know about it, and the majority of doctors would never consider enrolling their patients in a trial, as it requires a significant amount of time and resources for physicians, a scarce commodity in our modern healthcare system. Therefore, it is to their benefit if a patient, or a doctor on a patient’s behalf, reaches out to the trial coordinator to learn the details. For clinical trials, the recruitment process alone can be a very lengthy and costly process in order to find all of the eligible candidates. By reaching out to them, you might be doing them a huge favour, even if it can be somewhat intimidating at first. And once again, Clara can help out too.
What about the outcome of the clinical trial that my friend did not want to participate in? The latest data recently presented at the Connective Tissue Oncology Society 2017 Annual Meeting indicated that the experimental drug was very well tolerated and showing positive activity against cases of epithelioid sarcoma. So that is very encouraging news for future patients with this rare and debilitating disease. And as for my friend? Also doing just fine, so the choice appears to have been the right one!
This article has been produced by Merogenomics Inc. and edited by Kerri Bryant. Reproduction and reuse of any portion of this content requires Merogenomics Inc. permission and source acknowledgment. It is your responsibility to obtain additional permissions from the third party owners that might be cited by Merogenomics Inc. Merogenomics Inc. disclaims any responsibility for any use you make of content owned by third parties without their permission.
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