On clinical trials, creativity and patient adherence in cancer
"Let us honour if we can
The vertical man
Though we value none
But the horizonatal one."
WH Auden
Over the last few months, I've been having some interesting conversations with various people involved with cancer research and have been impressed with how many are going about looking at the clinical trial conundrum with a new and fresher lens. Sometimes doing the same thing repeatedly isn't always in the best interests of everyone, the researchers, doctors, patients, manufacturers, regulatory authorities.
The good news is that there are some new initiatives being discussed that break the mould from just looking at either first-line metastatic or relapsed, refractory disease as the first port of call in a isolationist nihilistic approach. This is good news and I'm hoping that more people taking on a broader, more holistic perspective will change the kaleidoscope of collective thinking.
Think about it.
What happens when patients stop adhering to therapy? How does that affect outcomes? What education is needed to help address this? Who should provide the education? Giving out pills boxes and chips in lids isn't going to change much without a link to why it matters.
At the recent EHA meeting, Jan Geissler gave an excellent overview of the broader factors affecting patients in two different sessions from the patient perspective. I hope it opened many physicians eyes to some of the underlying issues. This issue is nowhere near as simple as many may think. In a different session, David Mahon gave a fascinating talk on the impact of patient adherence on outcomes in CML based on some serious research. As one might expect, they were affected negatively, but the shocking piece of information was how many physicians encouraged dose holidays or skipping a dose, saying it wouldn't matter. This creates the wrong impression to start with.
More recently, the news that compliance with chronic tamoxifen therapy for treatment of hormone sensitive breast cancer is often poor, is not a surprise given the tolerability issues associated with the drug, but what is surprising is how little take-up this made in the medical news (HT Jody Schoger). How many women had a poorer outcome from their hormone treatment as a result of less than 90% compliance? What can be done about it? Very little comment or analysis in the medical press or advocacy world ensued.
In the end, we need more creative leaders working on this problem, a greater synergy between translational and biology research with clinical practice, cross functional working groups that involve multiple stakeholders, including patient advocacy, working towards a common goal for the greater good.
It is only when all of these factors come together in multi-functional teams that faster and better progress in cancer outcomes, in terms of both survival and quality of life, will ultimately be made. Where's that Cowbell when you need it?
What are you doing to help change things?
9 Responses to “On clinical trials, creativity and patient adherence in cancer”
Sally,
Thank you for such a thoughtful post. There is much work to do in understanding from a patient perspective the complex thoughts around compliance, adherence and persistence. Whilst RCT (randomised controlled trials) measure this rigourously in a very controlled environment we are very short of understanding exactly what is going on in the real world. We all (manufacturers etc) have an onus to really understand the service design issues right down to understanding what outcomes patients really want. It is difficult for us to understand the complex emotions going on for these patients at a time of intense uncertainty. I’m pleased you are one of those creative leaders hoping to cocreate a solution for these patients – count me in
Here is one more for the list of challenges with regard to the impact of compliance on clinical trials.
Osterberg and Blaschke published in NEJM that even in clinical trials, average adherence rates for chronic therapies are reported in the range of 43-78%.
One potential problem is that we then do an intent-to-treat analysis on all patients in the study, and use this data to report (and label) product efficacy and safety.
So if you are a patient who is 100% compliant and take the drug every day, are you “over-dosing” compared to the average patient in the clinical trial (who was, on average, only exposed to half to three-quarters of the drug doses)?
Another challenge in interpreting averages from large studies to draw conclusions about individual patient outcomes?
Thanks for your comments, Mike and Craig, lots of good points there.
I was vividly reminded of my own folly and ignorance in these matters during the last few weeks, remembering during that talks that we factored in a compliance rate of 80-85% in our forecast based on research available at the time and clinical feedback from the actual trials. That was a bit on the high side, clearly, even for a therapy that eventually had a clear proven survival benefit!
The difference between the controlled trial setting and the general cancer population for a given therapy is also different – in the latter, patients may be older, frailer, have co-morbidities, financial constraints etc.
The more one looks at this issue, the more it is clear that we don’t know very much and have a long way to go.
Craig, thanks for that paper, I’ll check it out.
Meant to include a link to the paper at NEJM: http://content.nejm.org/cgi/content/full/353/5/487
Sally,
I’m truly grateful for your thoughts and attention to this issue. The post I wrote about tamoxifen adherence continues to bring a variety of comments. What continues to alarm me is the silence from the “big name” breast cancer advocacy organizations, and zero response from groups “advocating” for young breast cancer survivors.
There’s much to do. Much more than I imagined. I’m on this, and appreciate your help.
Jody Schoger
Sally,
Interesting commentary and dialogue among your blog respondents. Is there any data on drivers of compliance within cohorts (i.e. does any data indicate if compliance is a problem with physician compliance to either SOC or research protocols or is the issue a greater problem among patients and perhaps supportive care givers)? The problem is likely multifaceted influenced by many variables including stage of disease, age of patient, length of treatment, direct physician involvement in education and support (more and more I see physicians spending less time with patients), etc. Another problem is that much of patient care in cancer is still disease centered rather than patient centered – i.e. researchers and practitioners are focused on disease eradication (which is important) and less on quality of life for the patients. Hopefully genomic medicine will improve in this area, but even at this individualized level, medicine is still focused on the disease rather than providing care for the person as a whole. You’ve raised a very complex and sensitive issue.
DT
My colleagues and I have just concluded one of India’s most in-depth studies on “Clinical Trials in India”. We have looked at various areas such as:
– Market Trends
– Growth Drivers
– Regulatory Bodies and Framework
– Major Players.
-Etc.
We interviewed over 200 individuals and firms to collect the data in what we believe is one of the most detailed study on the subject in India. If you are interested in a copy, you may email me at infoalcpl@gmail.com. It is a paid report.
Ashritha
infoalcpl@gmail.com
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Great blog with some super points covered. Thank you.
We would like to become an active participant within the cross functional group, helping care-groups, sponsors and CRO’s in a practical way.
Poor medication compliance and to a degree patient/caregiver education can be quickly fixed using simple, elegant, Patient Reminders.
How does it work?
Optimally timed, elegant, messages are automatically sent in the local language/font by SMS, email, iCal and voice helping everyone stay on track with:
– Visit attendance
– Medication reminders and alerts
– Protocol compliance for clinical studies/trials
– Fasting or sampling
– Dose titration
– Telephone interviews for safety or progress review
– Education, motivation
Messages are personalised for the different people supporting the patient:
– Family
– Friend
– Social services
– Improve attendance at social events
and can include important details such as site telephone numbers, zip/post code URL links etc.
We mainly work with sponsors and CRO’s in clinical studies, but we are proud to offer the Patient Reminder Software free for use by most non-profits and care groups.
Good luck with the mission. Let us know if we can help.
Kindest regards
Bernie
http://www.patient-reminders.com/
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