In the rare and terminal condition amyotrophic lateral sclerosis (ALS) there has been evidence from as far back as 2004  of patients violating protocol by taking experimental creatine supplements off-label when they were meant to be on the placebo arm. More recently, when a small phase II study reported that lithium carbonate might halt the progression of the disease in a small sample of 16 patients treated with lithium and riluzole relative to 28 patients on riluzole alone, patients rapidly mobilized to get hold of lithium off-label from their physicians. Within just six months a group of 160 patients had convened online and were tracking their disease progression, lithium blood levels, and side effects to discover whether they could crowdsource a study faster than the traditional medical establishment . In the end, an analysis performed by PatientsLikeMe showed that lithium had no effect , a finding confirmed by a number of clinical trials in later years . Some patients even went on to perform similar attempts at crowdsourcing while participating in randomized controlled trials, pooling their side effects to try and unblind themselves . Scientifically these protocol violations are a concern, but from an advocate’s perspective they seem like a reasonable reaction. Might there be a middle ground?
Patient centered trial design
A promising example from the iSPY-2 breast cancer trial suggests that integrating patients as informed decision makers rather than strictly as subjects may optimize study design, create better recruitment materials, minimize attrition, and ensure meaningful dissemination of trial results to women affected by the disease. Although it took more time and resources, the study investigators recruited up to 50 patients to advise, co-design, translate recruitment materials into other languages, and even sit on scientific advisory committees within the trial infrastructure . As a result blind spots were illuminated by patients before recruitment started and researchers managed to successfully enroll participants in a study with a fairly invasive protocol of repeated biopsies and imaging.
Another example comes from the Outcome Measures in Rheumatology (OMERACT) group, which invited rheumatoid arthritis (RA) patient advocates to participate in their bi-annual meetings to identify important outcome measures. Outcomes that matter to patients that had previously flown under the radar, such as fatigue, flare-ups, sleep disturbance, and foot pain were identified. Furthermore, advocates reported a cultural change that arises from having patients in the room when decisions are being made .