The case for electronic data capture in neurosciences studies is strong. The high failure rate in CNS development, headlined by a series of failed Alzheimer’s studies, is one reason to seek better methods. According to a Scientific American article by Kenneth Kaitin and Christopher Milne of the Tufts Center for the Study of Drug Development, a mere 8% of CNS drugs ultimately receive regulatory approval. In rare successes, clinical development of neuropsychiatric drugs takes more than two years longer than average.
Variability in endpoint data from neurosciences assessments is not the only issue in development of products in the neurosciences, but it is a big one. Electronic data capture and central ratings are two closely connected strategies for addressing such variability. Electronic capture of neurosciences endpoints as source data enables immediate central review of ratings entered at any site and earlier identification of outliers and underlying site issues. Furthermore, electronic capture of neurosciences assessments as source also eliminates transcription and associated errors and substantially reduces site-monitoring costs.
The industry is seeing a growing range of options for collecting e-Source data, including specialized tools that utilize smart phones or tablets and functions integral to general-purpose EDC systems. With personal computers, electronic tablets and smart phones virtually everywhere, it seems reasonable to predict that in future, a high percentage of CNS assessments will be available in a validated electronic format. However, we are currently in a transitional period in which some long-established paper assessments have yet to migrate to electronic media.
Establishing Equivalence of e-Source Assessments
Before utilizing e-Source assessments in a clinical trial, it is important to ensure that regulators accept measurement equivalence between the electronic version and the original print assessment. Depending on the extent of change in the assessment required to implement an electronic version, there may be little question about measurement equivalence. However, in some cases, establishing measurement equivalence may require proactive steps. Where migration to an electronic format requires only minor changes, cognitive debriefing and usability testing may suffice. Many assessments in the neurosciences, both for physicians and caregivers, and some assessments for patients, are simple numerical scales that utilize corresponding points on a paper assessment and radio buttons on the electronic device, where point and button each represent the same integer on a scale of 1-10. Opportunity for rater confusion with such an assessment seems limited and any validation required should be minimal.
However, when the electronic version of an assessment differs markedly from the paper original, it may be necessary to perform full psychometric testing to establish equivalence. This can be challenging if your development plans require use of a legacy paper assessment for which measurement equivalence of an electronic version has not been established. The need to validate an electronic version lengthens timelines and increases costs – effects that are particularly unwelcome in neurosciences development, where timelines are already long and costs high.
On the other hand, utilizing an immediately available paper assessment introduces delays in central review of assessments and requires data transcription and onsite monitoring – increasing risk and cost. Sponsors of studies in the neurosciences have often faced the Hobson’s choice between the delays and costs associated with validating an electronic assessment and those associated with transcribing and monitoring paper assessments.
The Time for e-Source Assessments in Neurosciences Trials Is Now
An increase in the number of e-Source modalities and a surge in venture backing for neurosciences development may accelerate the transition to e-Source assessments – venture capitalists have little tolerance for outmoded methods that reduce and delay return on investment. Authors of paper assessments who have not chosen to develop electronic versions of assessments on their own could help CNS developers by working closely with companies interested in producing validated electronic versions.
Patrick Phillips, DPhil, is Vice President, Clinical Affairs at Health Decisions. He has more than 20 years of experience providing executive oversight of clinical trials in all major therapeutic areas. Dr. Phillips’ experience in trials in the neurosciences includes studies of new drugs for Alzheimer’s disease, schizophrenia, Parkinson’s disease, epilepsy and Restless Legs Syndrome.