Expert Series: Associate Professor Nada Hamad on the importance of clinical trials
When talking to her patients, clinical haematologist and researcher Associate Professor Nada Hamad always considers their eligibility for a clinical trial.
“If there’s a study that’s good for someone, I’ll advocate for them to get access to that,” says A/Prof. Hamad. Regardless of whether the right trial for them is available at her centre, St. Vincent’s Hospital in Sydney, or any other centre in Australia or the world even. And the reason?
“We know that patients on a trial do better than patients who are not.”
A/Prof. Hamad has a strong interest in clinical trials. She’s the Director of the Haematology Clinical Research Unit at St. Vincent’s Hospital, President of Australia and New Zealand Transplant and Cellular Therapies, and the former Chair of the Bone Marrow Transplant and Cell Therapies Group at the Australasian Leukaemia and Lymphoma Group (ALLG).
“One of the most valuable things as a haematologist is to participate in clinical research,” says A/Prof. Hamad.
“By developing research or delivering it, as a site that refers patients to other trials, or by participating in the research world, defining the agenda, and moving the field forward, because that is what is best for patients.
“And the research side of clinical trials is a very important arm of our treatment arsenal as haematologists.”
“In this working environment, you don’t usually have people who look like me, and I believe in representation.
“I try my best to lead where I can and where I have something meaningful to contribute. It means I’m very busy, but it also means I have to be very smart about how I work and have efficiency in the things that I do.
“The transplant cell therapy space is an area that’s always been considered highly specialised because of how complex it is.”
She is “very grateful” for the specialty training she received at the University of Toronto at Princess Margaret Cancer Center in Canada.
“It gave me a different way of looking at the role of transplant and cell therapy. Once upon a time it was a treatment option when the patient had no other treatment options.
“A transplant doesn’t quite work the same way in everyone and it’s not as easy to deliver safely in everyone.
“Having the opportunity to study transplant in a very high-volume centre meant I got to appreciate and learn the nuances of managing different diseases with transplant.
“I got to see a lot of patients and learn how CLL (chronic lymphocytic leukaemia) transplant patients experienced this process compared to, for example, acute myeloid leukaemia (AML) patients. And I learnt that this treatment modality needs to be delivered in the context of what is available or becoming available in the therapeutic landscape.”
What is a clinical trial and what do clinical trials offer?
A/Prof. Hamad describes a clinical trial as “a study of treatments for a particular disease”.
“A treatment may be a well-established, in terms of how well it works and how safe it is, so the question of the study might be… how well does this established treatment work compared to some other established treatment?
“We call that a Phase III study which compares one option with another option.”
“The two options may be reasonably effective; we just don’t know which one is best.
“Those trials are fantastic because they offer patients clearly effective therapies, whether you’re on one side of the trial or the other. That’s what we call randomisation.
“Patients get a lot of benefit from the support of being on a trial as well. You’re getting the support of the research team, which does a lot of the heavy lifting, including organising appointments, supporting patients for travel, and making sure the patients are monitored very regularly and with great detail.
“A clinical trial offers a very high level of scrutiny and observation of how patients are doing on a study. This has to be rigorous, so patients on a trial often have better outcomes.”
“That’s probably because of the high level of care because it’s research and we need to gather very detailed information.
“In Australia, trials allow patients to access treatments that we know work but are not available on the Pharmaceutical Benefits Scheme (PBS) or are in the later stages of clinical trial research internationally and not available in Australia,” says A/Prof. Hamad.
There are other kinds of trials where the treatment has been shown to be effective and safe, but the effective drug dose, or the best dose to offer, may not be clear yet. These are called Phase I or Phase II studies, where A/Prof. Hamad said, “there’s still an exploration of the treatment strategy or the drug that’s being studied”.
“Those studies tend to be offered to patients who really have no other option, and access to a promising new treatment that could work for them when nothing else has been shown to work offers hope.
“That is one of my favourite aspects of clinical trials; being able to offer a lifeline in what sometimes can be a hopeless situation.”
A Leukaemia Foundation webinar, Understanding clinical trials, discusses the what, why and how of clinical trials to help you make informed decisions.
The role of clinical trials in progressing research
What people don’t realise, said A/Prof. Hamad, is the investment that is made in a clinical trial.
“It’s a very long process, making sure that the best minds in the world and the best science in the world come together to design and develop a clinical trial,” she explains.
“Often, we have sub-studies that run in parallel at the same time; new ways of diagnosing a problem or looking for biomarkers or blood test results that might give us a more accurate representation of what’s happening with the patient.
“So while clinical trials offer the patient an immediate treatment option, they actually provide the broader world of science and research, now and into the future, with more tools to deal with cancer, to improve the way we diagnose and the way we prognosticate and treat patients.
“There is a ‘greater good’ element that patients can contribute to, which is really quite immeasurable.”
“It’s the right thing to do for the future of the science that’s helping patients now.
“A lot of what we do now has come out of clinical trials, in terms of the kinds of blood tests we do, the diagnostic tests we use, and how we offer patients prognostic information.
“When a patient asks, ‘I want to know what I can get out of it’, I say, ‘CLL patients live with CLL for a long time and the research they participate in now may actually help them in the future.
“You’re really helping yourself in a bigger way when you have a longer-term disease like CLL by contributing to the research field which feeds into the bigger picture of how we treat blood cancers now, in the future, and forevermore. It’s part of history and it’s a very benevolent cause to be part of.
“Individually, you have a lot to gain by the detail that is required for clinical research. Every time you are in a study, the way that you’re examined by your physician, the blood tests that need to be done, have to be very detailed.
“The questions you get asked are documented rigorously, so nothing is left unasked, no stone is left unturned because for clinical research to be conducted well everything has to be extremely accurate and well-documented. That rigour should offer people a sense of confidence and accountability in how they’re being managed in a trial.
“The way clinical trials are supported financially means there are resources that sometimes we don’t have in the general healthcare system.
“We’re not going to pay you to be on a study,” said A/Prof. Hamad, but indirect financial support is provided to make sure patients are able to meet the requirements of participating in a trial.
“Not all trials will offer travel support, accommodation support, or carer leave support, but some trials do offer that because we understand how valuable that contribution to science is.
“The resources we direct towards trial patients tend to be well above and beyond what we have in the healthcare system outside of clinical trials.”
A/Prof. Hamad also emphasised that a clinical trial is not always the right thing for everyone.
“Not everyone who’s offered a trial should go on a trial. But if you have the opportunity, it’s really important to take it seriously and really consider it in collaboration with your care provider. Because the right decisions for you have to be the right decisions for you and not for a research study.”
Common misconceptions about clinical trials
A/Prof. Hamad said there were two misconceptions around clinical trials that she wished to dispel.
“The most common misconception is that people will be treated like lab rats, or they’re being experimented on,” she says.
“We’ve created such a rigorous level of oversight and governance and safety standards for clinical research conduct that the chances of that happening in Australia are essentially zero.
“And the international community has come together to develop principles and good clinical practice strategies to make sure that patients are never taken advantage of or exploited as has happened in past. The NHMRC and the medical profession take this very seriously.”
A/Prof. Hamad said another misconception is that patients often feel that if they decide or commit to a clinical trial, then they can’t stop or leave the trial.
“You can always exit a clinical trial,” she says.
“You can always decide it’s not the right thing for you – anytime, anywhere, at a drop of a hat. That is entirely the right of the patient.”
She also suggested that “with every trial, a patient talks to their clinician about what advantages it offers them, whether it’s directly or for the greater good, and what the patient’s rights are in the study, and what their obligations are”.
“Sometimes, a patient really wants to do a study for the hope it offers in terms of the treatment that it offers. For example, say you want to have CAR T-cells for CLL, and that doesn’t exist in Australia unless you’re in a trial.
“But if the burden of frequent visits and hospitalisation for the study are too hard for you to meet because you’ve got commitments to your family or the potential risks are unacceptable to you, then that trial may not be the right thing for you.
“So, the risk versus benefit to the patient and obligations and the rights of the patient within a study are really key components of discussions between a patient and their doctor,” says A/Prof. Hamad.
“It’s also important for us to support patients who are going through a clinical trial and to take as much time as they need to talk through everything and that they understand the information before they consent to participate in a trial.
“It’s about feeling comfortable with the decision to proceed.”
“To be honest, most of my patients jump at the chance. They are excited about it because they’re looking for opportunities and options, and I’d like to see more of that so patients understand that trials are a way that they can benefit and not a way that they are exploited.”
How do you find out about clinical trials you may be eligible for?
According to A/Prof. Hamad, there is no better advocate for you than your haematologist.
“That’s the right person to go looking for you because they know you with intimate detail and will be able to tell whether a study’s inclusion and exclusion criteria fit you or not,” she says.
“It’s much less efficient to go around asking multiple hospitals if you fit a study when you don’t really know the details of the study, but your haematologist will know you well enough to know what would be suitable for you or not.
“You have to ask them clearly, and say, ‘I am interested in clinical trials, I am willing to travel. Can you please find out what’s out there that I may be eligible for?’.
“And it’s important to let them know if you’re willing to travel, and whether you’re willing to travel to a different hospital or even interstate. Some patients even say they are willing to go international, so they would say, ‘please find out what is available for me anywhere in the world’.
“I do that for my patients because I’m the patient’s partner on their journey and I’m their advocate.”
“For patients who are very well-read and well-versed in their type of blood cancer, there are also online resources, like ClinTrial Refer, which is also available as an app,” says A/Prof. Hamad, who talks about this app in a short YouTube video: Clin Trial Refer A/Prof Nada Hamad Hematologist, St Vincent’s Hospital Sydney
“Most of my patients understand their disease, its stages, its severity, and what prior treatments they’ve had. They can do some of the research themselves if they choose.
“I’m very big on empowering patients to seek reputable resources for their education. There’s also clinicaltrials.gov, which is an international repository of all the studies in the world.”
A/Prof. Hamad said most international studies register with this website and there’s a ‘Search All Trials Here’ button on the homepage.
“If you enter a disease it will come up with all the studies available, their protocols, inclusion/exclusion criteria, and where they are being run, which is all public information.
“Obviously, local information is best, so asking your physician to help you find out what you would be suitable for is probably the best advice, but it doesn’t hurt, if you feel interested in pursuing other things, to go looking. But make sure you look at reputable sources.”
The need for more comprehensive patient data collection
Based on her academic work in intersectionality*, A/Prof. Hamad understands that sometimes there are at-risk groups that are invisible.
“I’m very focused on making sure that we’re inclusive of any form of vulnerability, and the way to do that is to think about what barriers to high-quality care might exist for individual patients,” she says.
“Even rural/regional patients are not all exactly the same. We tend to have a desire to homogenise vulnerable people; all women, all elderly, and all rural/regional.
“They’re not all the same. Some of them have more intersectional identities or vulnerabilities stacked up on top of each other that compound and make it very hard for them to get access to care.
“Some of my rural/regional patients are very financially stable, in fact privileged, so they can hop on a plane and come to St. Vincent’s Private and get the best and fastest therapy that they need. Some are not so I can’t really call them all the same.
“But what I can think about is making sure that healthcare outcomes are looked at with that lens.
“When we do an analysis of all the patients in a unit, and it’s very hard for us to do this kind of research in Australia, in my experience we’re not collecting that information in a way to help us make that analysis.
“For example, if you collect a patient’s ethnicity – if they’re Aboriginal or Torres Strait Islander – and you do an analysis, you might find out that they do better, or they do the same, or they do worse.
“But if you don’t collect that piece of information, you’ll never know because it’s in a big pool of data.
“What I’d like to see is a collection of data around a whole group of social determinants of health, including ethnicity, rural/regional status, gender, also financial status, literacy and migrant status, that are extremely important in a patient’s outcome.
“We know, from the literature and population health studies across the world, that for the best treatments we have available, some patients just can’t achieve those amazing outcomes.
“That’s a problem and we need to understand why that’s happening,” says A/Prof. Hamad.
“To answer the question around vulnerability, it’s really important to collect data and understand what are the vulnerabilities that we’re not seeing traditionally and start to proactively mitigate some of those risk factors, as if they were disease risk factors, because ultimately, they are.
“We know diabetes, and depression, increase your risk of a heart attack, so we try and manage those things.
“And we know your risk of getting a good outcome from your blood cancer is worse if you have certain social determinants of health characteristics, so we need to mitigate those also.
“I’d like a more concerted effort in our cancer plan nationally around that.
“I think that’s beginning to develop. The recent cancer plan identified the need to look at Aboriginal and Torres Strait Islander outcomes, and I’d like to see that grow a bit more so that we’re more inclusive of other potential social determinants of outcomes, so we can manage them as well.”
* Intersectionality is the acknowledgement that everyone has their own unique experiences of discrimination and oppression (gender, race, class, sexual orientation, physical ability, etc.) and offers a framework that focuses on the ways these multiple axes of inequality intersect and compound at macro and micro levels to produce a broad range of unequal health outcomes