When Trials Surprise Us: A Conversation with Dr Rasha Al-Lamee
Listening to Uncertainty in Interventional Cardiology
Mirjam Boros, Radcliffe Cardiology
Episode 149 of Parallax, a conversation between Dr Rasha Al-Lamee and Dr Ankur Kalra, where uncertainty, evidence, and clinical judgement quietly converge.
Clinical trials are often discussed as if their outcomes are predictable. Hypotheses are framed, mechanisms are mapped, and expectations quietly take shape long before the first patient is enrolled.
But this episode of Parallax reminds us that certainty is often an illusion.
“One thing I learned with ORBITA 1 is you can’t predict the result of a trial. It doesn’t matter what you think, it’s going to suddenly throw out an answer that you don’t expect.”
That observation sits at the centre of Episode 149 of Parallax, featuring Professor Rasha Al-Lamee. The conversation traces the evolution of the ORBITA programme and, more importantly, the mindset required to conduct research that genuinely tests belief rather than reinforces it.
Where the Question Began
The origins of ORBITA were not abstract. They emerged in the cathlab during routine clinical work.
“I had just done angioplasty on someone’s circumflex artery… and he said, ‘Why did you do that?’ And I said, ‘She’s got angina.’ Well, how do you know it’s going to make her better?”
The question exposed a gap between practice and evidence.
“We don’t really have the data on that, do we?”
From that moment came a broader enquiry. If symptoms are subjective, how should they be tested. And if a procedure is believed to work, what happens when belief itself is controlled for.
The Logic of Sham Controlled Trials
Sham controlled device trials are methodologically demanding and ethically complex. They require investigators to balance blinding with safety, and to speak honestly to patients about uncertainty and risk.
“If you’re going to look at a subjective endpoint such as pain, you have to test it against placebo in whichever experiment you’re doing.”
Designing ORBITA meant breaking down a familiar procedure into its component steps and deciding which were therapeutic and which were contextual. It also meant acknowledging what participation involved.
“There’s a 50% chance that they are exposed to some risk without any genuine physical benefit.”
When the trial was presented to ethics committees, the response was not rejection but curiosity.
“Well, why has no one ever done this before?”
When Results Defy Expectation
ORBITA 1 did not validate long held assumptions. Instead, it challenged them.
“If ORBITA 1 had just shown that stents worked and validated our preconceived beliefs, we may have stopped there.”
The controversy that followed did not close the conversation. It expanded it. ORBITA 2, ORBITA COSMIC, and plans for ORBITA 3 emerged not to defend a position, but to understand complexity.
“I wanted to understand why we’d got an unexpected result.”
The lesson was not that interventions never work, but that symptoms, mechanisms, and outcomes do not always align in simple ways.
Learning From Surprise
COSMIC introduced another reversal of expectation.
“I thought this device didn’t work and actually the device appeared to work.”
That insight altered clinical practice.
“I now put it in clinical practice because I do think that there is a device that’s useful for refractory angina.”
Across the programme, the unifying theme is not scepticism, but openness. A willingness to let data reshape understanding.
Rethinking How Benefit Is Measured
One of the most consequential insights came from how symptoms were recorded.
“Sporadic data points… really reduce the power of our trials to detect benefit.”
Daily symptom tracking revealed patterns that traditional follow up intervals obscure. It also highlighted a deeper truth about averages.
“While we get given an average effect, there’s always a range.”
The implication is clear. Understanding who benefits most, who benefits least, and why may matter as much as the headline result.
Practice, Guidelines, and Individual Patients
The conversation also reframes how evidence informs practice.
“If patients are still refractory despite multiple anti anginal therapies, it may not be their epicardial disease that’s causing their pain.”
Rather than rigid algorithms, the approach described is contextual and patient centred.
“I always tell patients that it’s unpredictable. I can hope for the best possible response, but every patient’s different.”
What Stays With You
What lingers after this episode is not a single trial result or device.
It is the discipline of not assuming you already know the answer.
“You can’t predict the result of a trial.”
There is something quietly grounding in hearing a senior investigator speak openly about uncertainty, and about allowing results to challenge intuition rather than defending belief.
The conversation stays with you because it resists simplification. Symptoms are not linear. Ischaemia is not binary. Benefit is not uniform.
“While we get given an average effect, there’s always a range.”
Listening to this episode is less about learning a new algorithm and more about recalibrating how evidence is held. It invites you to notice where assumptions have gone untested, and to remain curious even when answers are uncomfortable.
For those early in their careers, it offers permission to ask difficult questions.
For those further along, it offers a reminder that certainty should always be provisional.
This is not an episode that tells you what to think.
It leaves you more attentive to how you think, and why that still matters.
🎧 Episode 149 of Parallax is produced by Radcliffe Cardiology in association with MakeADent.org.