“Ethics” might be a small word, but in the world of neonatal clinical trials, it has big implications: these are the rules and guidelines that ensure research is done safely and fairly. It is the foundation of trust, safety, and potential progress for therapeutic advancements for neonatal-acquired HIE.
And few experts are more informed about the importance and power of ethics than Dr. Robert “Skip” Nelson, Ph. D. As the Executive Director of Pediatric Drug Development at the Child Health Innovation Leadership Department (CHILD) within J&J Innovative Medicine and the former Medical Officer for the FDA, he has spent years exploring ethics from the angles of research and regulation, striking a rare and unique balance between advancing medical treatments and protecting the safety of our most vulnerable patients.
Missed the live stream Q&A? No worries. We took notes, and like any good partner, we are willing to share! Read our key takeaways below.
HIE families have been at the forefront of groundbreaking research on HIE from the very start. They’ve contributed to cooling trials and other landmark studies and are vital to new and emerging research.
We can’t dispute that these studies are necessary for discovering potential treatments, but we also can’t deny that they present complex ethical challenges, especially when it comes to safeguarding our most fragile and vulnerable infants.
For families dealing with HIE, timing is everything. When a baby is diagnosed with HIE, there is a very short window for starting cooling. This urgency often doesn’t allow enough time for thorough conversations about consent: many parents in our community don’t have to work hard to imagine how hard it is to have a meaningful discussion with a clinician about the risks and benefits of cooling when the clock is ticking. To make it even more complex, there are many situations in which our parents are still recovering from their potential trauma or might not even be at the bedside or hospital when this conversation needs to happen.
That’s why ethical considerations are so important: they highlight the delicate balance between the need for rapid intervention and the right to informed consent. Studies need to be designed and implemented to ensure that our families understand the risks and benefits of participation, even when they’re under immense pressure.
As an advocacy organization that aims to support and educate families, we know this isn’t just a one-time discussion about ethics; it’s part of an ongoing process that helps protect our most vulnerable patients while pushing medical research forward. By sticking to ethical practices, we build trust and improve outcomes, which fuels more research and innovation. And so the wheel turns.
Views of ethical considerations in clinical research have transformed over the last few decades. Even as late as the 80s, the prevailing mindset was to view research cautiously, or as something our babies and other vulnerable populations needed protection from. It boiled down to this: if the research could introduce new risks, the priority should be safeguarding participants from these uncertainties.
Nowadays, the approach has evolved to a more proactive stance: we don’t protect from research; we protect through research. As Dr. Nelson says, there’s always going to be a potential risk associated with research and clinical trials, but ethics exist to ensure that research protocols are crafted with rigorous ethical standards, balancing these possible risks with the potential promise of significant benefits.
After all, without well-designed research, we lack the necessary data to make informed decisions about treatments and interventions.
When it comes to clinical trials, “informed consent” is a term many people have heard of, but it’s more than just a signature on a form. The essence of informed consent is that it’s both informed and voluntary.
For consent to be truly voluntary, it must be given freely, without any undue influence or coercion.
Coercion is pretty straightforward—if a physician says, “You have to participate in this study, or I won’t treat you anymore,” that’s clearly a problem. You’re being pressured to make a decision out of fear of losing necessary care, which undermines the voluntary nature of consent.
Undue influence can be more subtle. For instance, offering a payment to participate in research raises the question: is that fair, or is the promise of compensation overly influential?
Another layer to consider is how crises (like medical emergencies) impact decision-making. Some theorists argue that making a decision under such stress isn’t truly voluntary, while others believe that with skilled communication, consent can still be appropriately managed.
As Dr. Nelson explains, the process should ultimately adapt to the situation, ensuring that participants understand their choices despite any stress they may be under.
On the “informed” side, the question becomes: how much does a family need to know? In essence, how “informed” is “informed?”
It probably comes as no surprise that many consider informed consent processes overly complex and filled with jargon. Let’s face it: reviewing 20-plus pages of a consent form doesn’t always exude a sense of confidence or instill complete comprehension.
So, if parents or participants don’t fully understand all of the information, are they really giving informed consent?
To address these issues, the FDA introduced the requirement to focus on key information in March 2024. This guideline focuses on improving the clarity and accessibility of consent forms by emphasizing the presentation of essential details, but in a much more digestible format.
Here’s the caveat, though: just going over key information like, let’s say, adverse effects, doesn’t mean you can skip over all the other less common adverse effects. You can still only claim informed consent once all relevant details are shared. And when you think about it, it makes sense: if an adverse event occurs that wasn’t disclosed, for example, it would be natural for participants to feel misled, even if the outcome wouldn’t have changed their decision to join the study.
So, while key information helps improve understanding, the complete picture still has to be provided to ensure true informed consent. It’s all a balancing act that comes down to the time available and the transparency of communication.
The concept of “exception from informed consent” addresses situations where conducting research may be necessary, but giving standard informed consent is not feasible.
Here’s how some exceptions work, particularly in contexts that might be relevant to our community:
Even if consent cannot be obtained in the traditional way, researchers must make every effort to inform the parents or guardians and give them a clear opportunity to opt out of the study if they choose. This might involve contacting them as soon as possible after the intervention has started.
Research wouldn’t be research without encountering ethical barriers. While you may think that sounds like a joke, these challenges are an inherent part of the process. They arise from the essential need to conduct research with integrity, respect, and fairness while grappling with complex issues like consent, risk, and trust.
One major hurdle is the unexpected nature of medical conditions, like HIE. Unlike more predictable health issues, HIE often appears suddenly, leaving parents in a crisis with little time to think about, fully understand, or advocate for their child’s needs. These moments require immense trust in medical professionals and the research process. And despite advocacy groups’ efforts to do so, building trust isn’t easy, especially in the scientific and medical communities, where it’s common for parents to shut down opportunities for trial participation out of fear, confusion, and growing skepticism about science.
There are also moments in which clinicians strongly believe in the effectiveness of certain treatments, even if they are, as Dr. Nelson explains, “off-label” (approved for use in practice but not officially studied or sanctioned for that particular use). Convincing them to consider new treatments or participate in trials can be challenging, especially when they are confident in their existing treatments or therapies.
Another ethical challenge in neonatal clinical trials revolves around – you guessed it – funding, particularly for those that track long-term outcomes. This lack of funding can lead to incomplete data, forcing researchers to limit the scope of their studies and making it difficult to draw accurate conclusions about the long-term safety, effectiveness, and assessment of the risks and benefits of these interventions.
So, while ethical challenges exist, ethics are also the key to solving them. It all starts at the top, with policymakers and regulatory bodies setting clear guidelines and standards for clinical trials, establishing trust in the process, and ensuring that every aspect of the research is conducted with integrity and transparency. These then filter down to advocacy organizations, like Hope, that bridge the gap between the scientific community and the public, building trust through education and transparent communication. Let’s not forget the individual clinicians and researchers on the front lines who work hard (often with patient families) to design and conduct ethically sound and beneficial studies.
Dr. Nelson says there are a couple of valuable resources to consider for those interested in delving deeper into the ethics and guidelines surrounding clinical trials.
Beyond these resources, the power of engaging with advocacy groups cannot be overstated. According to Dr. Nelson, they have a big say in how FDA decisions are made, sometimes even more than clinicians do. Getting involved means families can better grasp the research landscape while also helping to advance it.
To watch the full live stream of this Q&A, visit our YouTube channel below, or click on our Key Takeaways for an at-a-glance view of this session!
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