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Cross my heart and hope to die should not be the promise brokered between healthy volunteers entering a clinical trial.

By Emma Sutcliffe on Feb 5, 2016

The great thing about the first few weeks of a new year is not the resolution-making, but the knowledge that you are facing the same thing that everyone else is – a liberating sense of impending failure before you ever really get started on those lifestyle changes. Mass failure. By February, after private and public declarations of change, you start to give up and revert to type. This year, I was going to resist drinking for the month of January, for example, and start my marathon training weeks earlier than usual. However, by mid-January, I was back to counting down the minutes to wine-o-clock (two children and two step-children will do that to you) and my new trainers are still sitting stubbornly in their box.

Informed consent is not patient centricity

In truth, people are reluctant to make changes, even when those changes are essential and will benefit our lives. Which is why companies making New Year Resolutions about patient centricity have to be careful what they wish for. They may change their mindset and create outreach programs; but are patients willing, able, equipped to join them in such changes? As much as the medical academicians Gigerenzer and Muir have described this as ‘The Century of the Patient’ and digimedical advocates like Topol turn out books entitled, ‘The Patient will See You Now’, how honest are we that all the declarations in the world may do little to effect long-term change. I also admire the stance of fellow polemicists, such as Ben Goldacre, that all trial data should be shared and pharma companies behave with transparency at all times. However, this is a utopian pursuit. Let’s consider the reality of these resolutions.

In the era of participatory medicine, patients may well be marginally more informed or seduced by the cyberchondria that Dr Google has to offer, but there’s still more evidence that patients are health illiterate than proof that they make truly informed decisions. Repeating verbatim what you’ve read on a website or in a social media community is more akin to an actor learning their script than a contextualised understanding of the body in disease, how drugs work or how clinical trials run.

Last month’s catastrophic phase 1 clinical trial in France, for example, emphasizes just how scientifically illiterate volunteers are even if they’ve signed an ‘informed consent’ form. One person died and five others were hospitalized after a clinical trial of an experimental drug went tragically wrong. Those few of us who actually have a decent understanding of clinical trials will know that phase I trials are conducted in healthy volunteers to determine the safety and dosing of a drug, before moving on to studies that test the effectiveness of drugs in people with a particular condition. This error in this particular clinical trial protocol may technically be attributed to intervals being too short between commencing ‘treatment’ between volunteers which is an essential component of a phase 1 clinical study to allow for emergence of adverse events to manifest before too many volunteers are exposed. It is excellent that our experts are straight onto this - “A key aspect is a proper interval of time between dosing of successive volunteers,” says biostatistician Sheila Bird of the Medical Research Council Biostatistics Unit at the University of Cambridge, UK, who is a member of the UK’s Royal Statistical Society working group, which focuses on 'first-in-human' clinical trials. But would the 128 healthy volunteers have had a thorough understanding of clinical trial design when they signed up and took the $2,060 payment? If we are truly patient-centric then we need to incorporate better health literacy on a global scale, earlier.

Patient equality is not patient centricity

Shared decision-making in health is now expected. Whilst that is a decent alternative to paternalistic medicine that patronizes a patient, it is also naive to assume that all patients are truly created equal or that Dr Google communicates equally with all patients.

Muir and Gigerenzer describe the ‘goals of the century of the patient’ as:

• Funding of research relevant for patients
• Transparent and complete reporting in medical journals
• Transparent and complete reporting in health pamphlets
• Transparent and complete reporting in the media
• Incentive structures that minimize conflicts of interest
• Best practice instead of defensive medicine
• Doctors who understand health statistics

We need to add public health literacy to this list.

Reality requires resolution that risk exists in medicine

Two people who are working tirelessly to plug the health literacy gap between patient inclusion and patient centricity are Dr Jon Stamford and Dr David Gillen. As a neuroscientist and a cardiologist respectively, each individual is focusing on what they can do to ‘make’ better patients and better clinical trials that see a resolution of partnership a resolution that lasts beyond hype. Dr Gillen has had roles in pharma R&D for twenty years, at Wyeth, Pfizer, Gilead and most recently as Head of Patient Safety at Celgene. During his career, he has highlighted some of the challenges that are involved in creating clinical trial protocols for drug development. Dr Gillen is always honest even when it could be argued that honesty may not be the best policy for harmony: “patients are unclear about the degree of uncertainty in medicine, yet more and more patients want to be included in decisions and trial design and it is very difficult to communicate uncertainty as it leads to patient dissatisfaction. It’s a vicious circle.”

Physicians and industry alike struggle to thoroughly outline risks and benefits to patients. For example, in their 2012 publication, ‘Risk communication and the pharmaceutical industry’ Edwards and Chakraborty explain that, ‘risk communication is central to the risk management strategy of a pharmaceutical company. Pharmaceutical companies primarily communicate risk through labelling tools such as the Summary of Product Characteristics (SmPC), package insert, patient information leaflet (PIL) and the pill packet itself, which are currently regulated based on templates such as those of the EU. Recent research raises concern about how effective the SmPC is alone in communicating risk. A pharmaceutical company is not the only stakeholder responsible for communicating risks on their products.” Indeed, this same research confirmed that over-zealous risk management by companies or confusion about the overlap between symptoms of a condition and adverse events from a medication taken to treat the illness is a substantial problem. There is frequent misattribution of symptoms as drug adverse events.

Other problems in patient health literacy include basic medical and pharmacological statistic fog. David Gillen startles me by explaining that ‘if you ask a patient, would you be more concerned about an illness you have a 1 in 10 chance of contracting or a 1 in 100 chance of falling prey to, the majority of people would think the 1 in 100 statistic was more ‘scary’.’ As a Medical Biochemist by training, I’m familiar with interpreting stats – but I confess that even I have to double check on confidence intervals, relative risk ratios and numbers to treat when I read a clinical trial protocol. So it’s not too much of a leap to realize that informed consent by patients who do not have the benefit of my 20 years in pharma may not actually truly understand medical or clinical trial statistics.

Jon Stamford describes himself as “something of a strange hybrid in the sense that I'm both a scientist and a patient. My first degree was in pharmacology way back in 1980 which stimulated my interest in neuropharmacology and neuroscience, which I pursued to PhD and beyond. Much of my research centered around the brain dopamine systems, a particular irony when I was diagnosed with Parkinson's disease in 2006”. Dr Stamford currently works for Cure Parkinson's Trust and is principally responsible for directing Parkinson's Movement, a patient engagement arm of the CPT, of which he was a co-founder in 2010. Jon is committed to identifying areas  and ways to help to channel the patient voice and patient experience into improved medical practice. Like Dr Gillen, Jon is candid that including patients in clinical trial design is now an essential. Jon explains, “Without successful trials, new medicines are not introduced, new treatments are not developed, and new understanding is not gleaned. The furtherance of knowledge hinges upon the successful design, execution, and interpretation of clinical trials. Yet too many trials fail and poorly designed studies, with little consideration to real world concerns, are doomed to failure. One of the most commonly cited reasons for failure of a clinical trial is patient recruiting and/or compliance. Patients drop out of studies, for a variety of reasons. And many a researcher bemoans the high dropout rate in some more expensive and extensive trials. Often the blame is explicitly placed firmly at the feet of the patients, and patient culpability can be assumed. The solution is breathtakingly simple. Involve patients. Involve patients in every step of the process from conception to execution. Only when patients are involved in protocol design will the outcome be a clinical trial that is realistic, pragmatic, and attainable.”

Jon is an idealist, but also a realist who recognizes that there is much more work to be done on patient literacy to achieve this goal and recognizes that patients won't always be able to make truly informed decisions about a treatment. In Jon’s words, “As a patient advocate, I would like to believe that patient-generated data is by definition a closer indicator of patients self-perception of health. The difficulty in many respects lies at the boundary between patient and physician, attempting to persuade the physician that self-generated patient data is meaningful. But to be honest, that will probably always remain a credibility gap between patient and physician.”

In 2016, I’m going to shift my proselytizing about the need for patient centricity in pharma to pushing for patients to receive better education about the risks in pharmaceutical medicine. We need to resolve to communicate better about the risks and help patients make truly informed decisions. Cross my heart and hope to die should not be the promise brokered between healthy volunteers entering a clinical trial. The time for stamping feet about patient centricity has passed. Participatory medicine needs to get real and that includes that we resolve to be better patients too and don’t just rely on industry and medics to inform us but we also seek to inform ourselves.