‘Real-life’ data collected through social networks are a viable, speedy and low-cost option for supplementing the results of randomised controlled trials and supporting effective decision-making both in research and development and medical practice, a new observational study has concluded.

The patient-initiated study of the potential effects of lithium carbonate on disease progression in amyotrophic lateral sclerosis (ALS) was designed and managed by PatientsLikeMe, the US-based online platform for the exchange of health data, which is used by more than 100,000 patients. The results were reported in the journal Nature Biotechnology.

The context for the study was the tendency of patients with serious diseases to experiment with drugs that have not yet gained regulatory approval.

“Online patient communities structured around quantitative outcome data have the potential to provide an observational environment to monitor such drug usage and its consequences,” suggest Paul Wicks and colleagues from PatientsLikeMe (all of whom hold shares or stock options in the company) in their Nature Biotechnology report.

Lithium promise

The specific trigger for this approach, which PatientsLikeMe says is the first instance of a social network being used to evaluate a treatment in a patient population in real time, was research published by Fornai et al in early 2008 suggesting that lithium could slow the progression of ALS.

This was a small, single-blind trial of 16 treated patients and 28 controls, Wicks et al note. Despite the scepticism of the medical community, though, some ALS patients were sufficiently encouraged to start gathering data on their use of lithium using an online spreadsheet.

PatientsLikeMe then built a lithium-specific data collection tool to capture information about the 348 ALS patients registered with the website who had started taking the drug off-label via their physician.

To see whether the effects reported in the Italian study could be corroborated in these 348 patients, PatientsLikeMe decided to conduct an observational analysis of self-reported outcomes using the Revised ALS Functional Rating Scale (FRS, which measures patient-reported functional impairment in areas such as speech, walking and respiratory function).

When the dataset for the study reported in Nature Biotechnology was finalised, there were there 4,318 ALS patients in total on PatientsLikeMe, all of whom were invited to report their FRS scores, symptoms, treatments, site of ALS onset and demographic data using online tools provided on the website. Of these, 3,674 (85%) provided at least basic demographic and diagnosis data while 348 of them (9%) reported taking lithium.

After inclusion and exclusion criteria had been applied, 149 patients remained eligible for subsequent analysis in an ‘intent-to-treat’ group (i.e., they took lithium but may have discontinued it within 12 months) and 78 patients were eligible in a ‘full course’ group (a subset of the intent-to-treat group who continued to take lithium for the entire 12 months).

Matching algorithm

To reduce potential bias owing to the lack of randomisation in the study, PatientsLikeMe also developed an algorithm to match the 149 selected patients to multiple controls (447 in total) based on the progression of their disease.

For each patient taking lithium, the algorithm matched multiple controls from the website’s historical database “that had as similar an FRS trajectory as possible to the treated patient’s disease trajectory from onset to start of lithium”, Wicks et al explained.

The outcome was that, 12 months after treatment, no statistically significant differences in FRS scores were found between lithium-treated patients and matched controls in either the intent-to-treat or the full-course group.

These findings not only failed to replicate the promising results seen with lithium in ALS patients in the Italian trial. They were also in line with subsequent randomised clinical trials of lithium in the US and Europe that were halted early for futility due to lack of detected efficacy in ALS and to safety concerns, the authors note. 

Limitations, advantages

While the report in Nature Biotechnology acknowledges the many limitations inherent in studies using self-reported data and historical controls, it also points to a number of potential advantages in collecting patient-reported outcomes data online.

These are listed as speed (there was only a nine-month gap between initiation of the data collection tool and publication of preliminary results from the ALS study), patient access, the availability of control participants, low costs and patient engagement. 

“Positive results from Phase I and Phase II trials can lead to changes in patient behaviour, particularly when a drug is readily available,” the authors comment.  “The ongoing availability of a surveillance mechanism such as ours might help provide evidence to support or refute self-experimentation.”

Indeed, they add, during the study it was reported that clinicians were citing preliminary results available on the PatientsLikeMe website as a way of dissuading patients from self-experimenting with lithium.

“While not a replacement for the gold standard double-blind clinical trial, our platform can provide supplementary data to support effective decision-making in medicine and discovery,” said PatientsLikeMe co-founder Jamie Heywood. “Patients win when reliable data is made available, sooner.”