One of the areas that I have felt for some time as being a compromise to the effectiveness of EDC, is the subject of Source data, or rather, the fact that source data is often not entered directly into an EDC system.
I appreciate that we have situations where this is impractical for logistical reasons – location of computers, circumstances of source data capture etc.
However, often, it is mandated by the sponsor that source data is not logged in the EDC system, but is instead recorded elsewhere first. Some advocates will indicate the need to comply with the regulations that state data must remain ‘at the site’. Personally, I don’t concur with this assessment. The data is ‘at the site’. The cable connecting the screen to the computer might be very very long (the internet) but the data is constantly available at site. I probably shouldn’t be flippant on this point, but, the conservatism in conflict with progress strikes a nerve.
Transposing information from paper to an EDC screen introduces the potential for error. In the old world days of paper CDM, we had Double Data Entry as a method to confirm transcription errors did not occur – 2 staff enter the same data from the paper CRF’, and the differences flagged/corrected. With onsite EDC we don’t have Double Data Entry, but, we do have Source Data Verification. Instead of 2 staff sitting next to each other double keying data, we have a monitor fly in to perform the 2nd check. Yes, I know, they carry out other duties, but still. This seems like an enormous effort to check for transcription issues. It also has a massive effect on slowing down time to database lock.
So – where are the solutions:-
1). Data at Site
We could put on our ‘common sense hats’ and make a statement that allows the entry of source data into the online EDC system. I know of a number of EDC companies that have simply placed this in their procedures. No audit findings / concerns have been raised as a result that I am aware of. Come on Regulators – why the delay in making a statement on this subject? The confusion caused is creating a measurable delay in bringing drugs to market!
2). Physical availability
This one is harder to tackle. When you have data to log, do you always have access to a system/device to log the data? Possibly not. Do you simply try to remember it, like an Italian waiter remembering a dinner order… I don’t think so. We either need to provide portable data entry devices, or, we accept paper transcription for these elements.
3). Differentiating Source from eSource
This does open up one area of concern. If we have some data as source, and some as eSource, how do we know which is which? When a Monitor goes looking for the source data, if they don’t find it, does that make it eSource – no. There needs to be some very simple flagging, and visual indication system built into such a mixed source/esource system that supports this. I have seen this in one system, but, it is very rare. Come on EDC vendors – you’re turn here!
4). Other systems
Health Record systems amongst others will often be the first point of entry for data that may apply to an eCRF. The current approach for organizations such as CDISC and HL7 is to create interfaces between systems. This will be a slow burner, I predict. There are so many hurdles in the way. It requires active cooperation from both sides – EDC providers may be fully onboard, but, I am not so sure about most EHR providers.
We may see a company emerge (maybe this is what some former PhaseForward employees are up to – who knows!) develop an online Clinical Development Electronic Health Record System that is immediately EDC ready. Of course, with such a small deployment potential, I am not sure that we will see this appear at all sites in a global study, but for domestic application – say within a single country, inside research hospitals, it could work. I digress – back to the integration issue – yes, when we have standards, the feeds will start to happen, but not for many years.
5). Patient Recorded Information
ePro, Patient Diaries etc. These are increasingly realistic, for the right sort of study for the accurate capture of patient data. If used appropriately, they can cut down the volume of data that needs to be transposed into EDC, and therefore source data verified.
On a side note, I am sure we will see a downloadable iPhone app that will make the current hardware/software dependent or basic PDA browser based systems seem old and tired.
The advantage of diary based systems is that instead of an investigator quizzing a patient, writing down the responses, transposing the responses etc. The information is captured ‘at source’ often considerably closer to the time of event.
Expanding from my previous post, I expect to see systems like PatientsLikeMe expand onto portable devices and act as an entry point for both patient identification and data entry. Internet enabled device pervasiveness will simply make this happen.
Conclusion
A lack of eSource has direct impact on the time it takes to lock data. With adaptive clinical trials executed by forward thinking sponsor companies, the point at which an adaption can occur corresponds directly with how long it takes for the sample size end-point significant datapoints to achieve a locked status. To simplify – the less eSource you have, the longer your studies will take. Forget a few days – we are talking wasted months.