“Doctor, should my dad enter a clinical trial?”
Nearing 80, my newly diagnosed cancer patient is like many people his age. He has a few health problems, none compromising his physical fitness, but the family has begun noticing some inattention and forgetfulness. He jokes that his “hearing issue” is that people drive him mad and he just wants to read quietly.
As we talk, I warm to the duo – the former factory-worker father comforted by the presence of the scientist son who has questions I wish everyone asked.
Oncologists are taught to ask themselves at every juncture, “Is there a clinical trial for my patient?” Awareness campaigns and advocacy groups have prompted more patients to ask the same question.
Trials are an opportunity for patients to benefit from promising treatments that are not yet standard care. While the overall possibility of success for a drug to go from the earliest trial phase to market approval is a low 3%, the figure rises to a healthier 24% if the drug makes it to a late-trial stage. Patients enrolled in well-run clinical trials may have improved outcomes, helped by greater adherence to guidelines and protocols. Along the way, researchers discover valuable evidence and serendipitous findings to improve care for everyone else not on a trial.
For all these reasons, I want to say an enthusiastic yes to my patient’s son. But, being a scientist, he has some considered questions.
How many elderly people take part in clinical trials? In other words, are clinical trials a young person’s game?
Are there differences in outcomes and tolerability between white and non-white patients? His father is Asian and, anecdotally, their relatives had had especially poor experiences on chemotherapy.
And, most importantly, what does the quality-of-life data show? At his age, the father is less focused on survival than avoiding disabling toxicities that would threaten his independence.
To these excellent questions, my answer is a paltry, “We don’t know.”
It feels like an “emperor has no clothes” situation: while avowing the importance of clinical trials, the most basic inquiries have left my profession exposed.
For a start, there is this flat admission from the Australian government:
The number and proportion of adult cancer patients enrolled in clinical trials is currently not known in Australia. As a result, an understanding of unwarranted variation in clinical trial participation between population groups is also not known.
In one Australian state, just 5% of adult cancer patients were enrolled in a clinical trial, with 83% of participants based in a major city. This is broadly consistent with global figures.
Globally, more than half of cancer patients are over 65 but many trials either have an age limit or effectively exclude elderly people due to a previous cancer diagnosis or other common conditions.
The few elders who meet the inclusion criteria are the “rock stars of older adults” who are healthy enough to meet the criteria for enrolment.
By these exacting standards, more than half of Australian adults with lung cancer would be ineligible for a trial.
Companies that spend big bringing a drug to market don’t want to cruel their chances of approval based on unacceptable side-effects, which are worse in those with reduced physiological reserve. These people are typically, though not always, over 65. But excluding “regular” people from trials does us a huge disservice because, once a drug is approved, it is prescribed to just such patients. They might have concomitant conditions, take multiple medications, be cognitively impaired, have mental illness or lack social supports. Treated by “trial criteria”, they rapidly become the patients who languish in hospital, lose their precious independence, and regret having said yes to treatment. When they suffer, society loses.
We can’t urge cancer patients to enter clinical trials only to make the task herculean.
Quality-of-life data is paramount for shared decision-making. Any prospective trial patient deserves to know: how did the other trial patients feel? Did they sleep well? What happened to their social life? Could they keep working? How did their family cope?
Still, in one analysis of phase 3 clinical trials (the kind that lead to regulatory approval), 47% did not even bother to study quality of life and, of the ones that did, almost 40% didn’t care to report it. Astoundingly, researchers saw fit to not publish quality-of-life data for up to eight years after the trial closed.
This practice is ethically dishonest, not to mention disrespectful of trial patients who arm scientific progress without necessarily deriving personal gain.
When clinical trial meets real world, there is much room for lament but it need not be so.
Australian regulators can reinforce the place of “regular” patients in clinical trials. Drug companies should be required to study and submit quality-of-life measures as a condition of approval. In a country where 30% of the population was born overseas, data on ethnic differences in treatment tolerability is not merely desirable but essential.
My patient’s son is uneasy with the lack of answers to his most important questions. To add to his hesitation, I can neither promise the availability of an interpreter nor medical transport if the son could not take time off for the frequent appointments.
For this patient, the barriers to a clinical trial are too many so he declines it. He is not alone.
If one measure of high-quality cancer care is clinical trial participation, our work has just begun.
Ranjana Srivastava is an Australian oncologist, award-winning author and Fulbright scholar. Her latest book is called A Better Death
