It is not inaccurate to say that using paper diaries in research today borders on the unethical, and if nothing else, it is a manifest waste of time and money.

As I was writing this column, we had a sign from heaven – or at least Rockville: the FDA had issued its Final Guidance for Industry on Patient-Reported Outcome Measures. If ever there was a “pro” for ePRO (Electronic Patient-Reported Outcomes), this is it. There is nothing that garners the attention of biopharma executives like a statement from one of its key regulators, and the Guidance is welcome news to those of us who have advocated for a wider use of PRO data with the reliability that an electronic means of PRO collection brings. I couldn’t have asked for a more timely coincidence.

Pros over Cons

Let’s look at the “pros” of ePRO in three ways: pros, pro’s, and prose. Let’s assume you have a product in clinical trials that needs data recorded directly by the patient, either at home or in the clinic. You will use this data to investigate a primary or secondary endpoint, and as such, this data is essential for your understanding of the disease, or your product, and of patient experiences of both. Simply put, if this data is needed for this kind of research, you cannot use paper-based methods of collection anymore. The worthlessness (inaccuracy, untimeliness) of this data is now well accepted, beginning with anecdotal evidence experienced by researchers decades ago and proven in controlled examination like that published in the British Medical Journal in 2002 (Stone, et al., Patient non-compliance with paper diaries, BMJ 324: 1193, 18 May 2002). It is not inaccurate to say that using paper diaries in research today borders on the unethical, and if nothing else, it is a manifest waste of time and money. Use “e” methods for PRO or nothing at all.

But there’s more. What’s often missing in the discussion in favor of ePRO is the change in science that is enabled by knowing you now have methods of data collection which will support the validity of asking research questions which you could never do before, with any scientific rigor. So while safety and disease efficacy will always be important quantitative goals of clinical trials, you can now explore if and why your candidate may be superior to other treatments based on the qualitative dimensions commonly lumped under umbrella terms like “quality of life”, “health outcomes”, “health economics”, or “evidence-based medicine”. In some respects, these non-specific terms have misled the listener and undersold the impact that an imaginative study design can now bring to the research program. Creating new market opportunities, and new means of improving patient health, await.

While this column is focusing on pros, not cons, perhaps one of the biggest challenges to widespread substitution of paper PRO with ePRO is the perceived disproportionate cost of “adding” ePRO to the study budget. Without going into great detail, a simple characterization of this issue is that ePRO services today rely on a (yet another) third-party vendor, with their own bid, their own quotation of cost, which is thereby easily identified by study teams as “incremental”. Besides missing the understanding that paper PRO also costs something, I think there is a way around this: ePRO is another means of EDC in clinical trials (a characterization I have resisted in the details because I am too close to the trees to see the forest). In this sense, it becomes comparable to the (now forgotten) debates over electronic central laboratory data. So the chain of reasoning is the same: if ePRO data is really important to you, you should (and perhaps must) collect it electronically, just as you would, in 2010, collect most any other trial data. In other words, it is not a discretionary cost. If you need it, you need to spend it. If you don’t need it, don’t spend it (and live without that data).

The Pro’s at Work in ePRO

Are there “pros” (professionals) in ePRO? This question has been a legitimate concern of the biopharma industry as we have watched ePRO vendors struggle to create a new market from scratch, learn the processes and logistics of a new research methodology, correlate the important scientific component, and try to scale to the volume of studies where ePRO use is possible.

Although the vendor community is still maturing and does not compare in top-to-bottom professionalism of say, the EDC vendor community (or that of vendors for statistical analysis tools or document management or safety monitoring), the ePRO vendor universe has several admirable, time- and trial-tested providers for biopharmas to lean on. As always with a technology market, older ePRO companies are getting much more professional in the “soft” side of their offerings (services, logistics, science consulting) while their software and hardware technology tends to lag, and the new ePRO companies sometimes have more exciting technology but insufficient experience in the soft side.

It’s important to keep the technology and the services separate. Unlike other clinical development IT spaces, where the technology has become very similar vendor to vendor, technology still matters in ePRO. And it is a bedevilment that we still don’t quite have the magic, one-size-fits-all, ideal hardware platform and may never. This is challenging for the vendors, but also for their customers. Sponsors looking to make long term commitments to ePRO are understandably confused about the myriad of hardware choices and accompanying software platforms, and this leads to a reluctance to commit to any one approach, while accepting ePRO conceptually.

The service component is particularly critical in ePRO because, for now, it needs so much support. This support primarily comes from the vendor since sponsors are not, or cannot, absorb ePRO capabilities internally. Services are also critical because, as with most clinical development IT, sponsor processes are not mature, tailored to the tool and optimized for individual sponsor efficiency. This affects all aspect of ePRO services including logistics, supply, support, helpdesk, workflow process, and project management. Most vendors today show an uneven professionalism in services – some are true pros in logistics, some are rapid study designers, others have been lucky with their project managers.

On the other hand, one area where a large handful of providers are truly professional is in the science of ePRO – the development, tailoring, selection and validation of the “instruments” (questionnaires) that are chosen for administration on ePRO devices.

Where is the Prose?

Perhaps what is missing the most at the moment is the prose about ePRO. That is, we are still not talking enough about ePRO, to the right decision-makers, with the most appealing contentions and data, to have ePRO become as widely used and uncontroversial as central lab data, or even EDC. Clearly, not enough clinical development personnel understand the horrors of paper (since we are still doing paper PRO studies), nor do they understand the potential for new scientific explorations possible with valid patient-reported data. For some reason, ePRO remains at best the province of biopharma’s marketing guys, or “outcomes nerds,” and PRO is viewed as a “last resort” and not “real” research. This is an antique attitude, and it contributes to the resistance to funding ePRO services. The vendors have probably talked enough; sponsors must start writing and speaking more clearly and openly about their success with ePRO on the one hand, and any lingering concerns on the other hand.

The pros of ePRO are clear. The professionals of ePRO are improving. We need more prose on ePRO so that all are well-informed about when and how ePRO should be added to the clinical development program.