The advantages to clinical trials of electronic data capture are (somewhat paradoxically) both well-established and yet to be fully experienced. The sudden and recent boost to the power, accuracy, and speed of data capture, transfer, storage, and analysis is clearly promising, though it has yet to show its full effect.
However, as more trials make the shift from classic pen-and-paper CRF to the more modern and versatile eCRF systems, it’s a good bet they will continue to outcompete those who are slow to make the change. If you’re still wondering whether it’s worth switching, it’s important to know not only what the benefits will be, but what it will cost in terms of financial, human, and time factors.
The Role and Benefits of Using eCRF Data in Modern Clinical Trials
In the simplest terms, eCRF is the electronic version of the common Case Report Forms (CRF) that you might be familiar with. Paper CRF were the main forms used for capturing data from medical devices and have traditionally shown up in trials as A4 sheets with carbon (or NCR) copy leaves attached so that one version can be torn off and added to the master file.
These are still in use in a lot of places: usually, sites where small-scale studies are being run. Generally, though, they’re being phased out and you’d be a lot less likely to see them in larger or international studies.
Instead, they’re being phased out by the eCRF, which has already shown improvements over the old forms in a number of ways, including:
- Anyone can access eCRF data, wherever they are, from the moment it’s entered
- eCRF data can be uploaded in much less time than it takes to fill out a form
- The data then don’t need to be duplicated or re-entered elsewhere
- Data can be shared with ease between relevant personnel (and kept safe from others)
- Reports can use the most up-to-date and complete sets of data throughout the study
- Data is logged, stored, and transferred more securely than with paperwork
- There is improved transparency throughout the clinical process as stakeholders can access the data relevant to them when they need it.
We’ll go over some of these benefits and why they’re significant in more detail in the coming sections, but as a summary, eCRF represents a streamlined and more secure way to manage CRF data. This has a cascade of positive effects on the speed and power of clinical trial execution, bringing better data to the table faster, and ultimately saving money and improving the results of clinical trials.
eCRF represents a higher standard of data collection, but more than this, it also speeds up the entire clinical trial process, and when planned and designed well, it can entirely illuminate some forms of human error. All of these benefits ultimately translate to a faster trial process, which positively impacts the bottom line for sponsors, improves the patient experience, and brings drugs to market sooner.
In order to really highlight these advantages of good eCRF design, it’s worth looking at the classic CRF design attributes for comparison.
Standard Case Report File Design
From a 2014 paper in Perspectives in Clinical Research, we can get an idea of some of the most important factors that should be considered when designing a CRF. We’ll come back to these factors in the later section to show how they are improved upon by the eCRF.
- All CRF paperwork should be designed with completeness and accuracy in mind.
- It should be well-structured, and easy to complete.
- It should collect relevant data of high quality.
- It should collect enough data without ambiguity but at the same time avoid redundancies.
- CRF data should be collected where possible in a way that helps with statistical analysis and interpretation.
- Each document should contain identification of protocols, subject ID, and a space for the investigator’s signature.
- Forms should be uncrowded and easy to read to avoid data discrepancies.
- Questions should be concise and clear, and formatting should be consistent.
So essentially, an effective CRF design needs to be user-friendly, while able to capture legible, accurate data of the quality and quantity needed for effective analysis, and without capturing redundant information. On paper, this can mean several pages, with notes where appropriate relating to which parts of the form to skip and which need filling in, and text that alerts the participant to how many decimal places are needed, or whether the text should be in capitals or lowercase.
Each page also needs to have a date attached, and the format must be consistent. For as many answers as possible, it’s best to use yes/no options or some other form of multiple choice to standardize the answers. The fewer opportunities for free text entries, the better, as these are where data inconsistencies tend to crop up the most.
Forms should be completed on NCR paper to ensure an exact replica is formed at the time of completion. Should the design of the CRF form need adjusting during the trial, all previous uncompleted versions need to be recalled and replaced to ensure only relevant forms are available.
As you can probably see, there are some significant limitations in designing CRF the old-fashioned way, and for all of these needs, electronic versions promise to provide an improved and enhanced version of CRF data without sacrificing any of these requirements.
eCRF Design for Clinical Trials
As mentioned, an eCRF is essentially a digital version of the above, and as such, it shares a lot of the design features. The basic form components of the eCRF are there to facilitate the goals listed in the first section and offer significant improvements upon them at the same time.
Taking a basic form as an example, most effective eCRF designs will use similar fundamental components, including:
- A Form Label – This is a descriptive label for the form itself, explaining the kinds of questions contained in the form and helping to differentiate one type of form from another.
- Group Label – If the form contains a lot of information, it’s useful to group it into categories. Each of these will get its own group label on the form. In any form, there can be recurring groups or no groups at all. This will all depend on the amount of data that’s required.
- Item Description – This is the prompt for the entry of electronic data. For example, it might be a short term like: ‘Blood Pressure’. Each data field on the page needs to have a relevant item description to tell the person filling it what needs to be entered.
- Data Field – These are the empty boxes in which participants can enter their data. This can be in a drop-down menu, a checkbox, or an empty space for text or numerical values. Data fields on eCRM forms can be capped at the appropriate decimal places and can change color on completion to signify whether the data entered matches the expected format.
- Data Validation Field – If data entered into the form is flagged as outside the range of criteria set by the form design, a message can appear on the form explaining how to rectify this. These edit checks are particularly useful for ensuring all entered data matches the format required for analysis. They can also spot where fields have been left blank and either restrict the form’s submission until they’ve been rectified or prompt the user to confirm that said field is intentionally left blank.
This then becomes quite literally an electronic form, and while it’s filled out similarly to a pen-and-paper form, this document has the ability to guide the user much more effectively in the format, quality, and accuracy of their inputs.
So, while the same design criteria are generally applicable for both CRF and eCRF forms, the advantages of the latter over the former should start to become clear. Next, we’ll delve a little deeper into precisely how eCRF clinical trials data is superior to its paperwork-based predecessor.
Trials Should Phase out Paper CRF for More Accurate, Faster, and More Secure Data
We’ve focused a lot on the roles and benefits of good CRF, but it’s important when making a case for switching to eCRF that we highlight exactly the limitations and drawbacks of using pen and paper to collect your data. Here are three of the major issues with traditional CRF:
- The first issue is speed. CRF needs to be drawn up for each case at the design stage of the trial, and this alone takes a substantial amount of time. But where eCRF can be rapidly edited and updated, making changes to CRF documents can involve complex version control processes to try and ensure all relevant outdated documents are returned and replaced.
The time it takes to access data is also an issue. With paperwork, the documents need to be filled in manually, then submitted, then transcribed to a repository. Only then can the information be accessed remotely. This process is not only slow but leaves room for error, leading to the next issue.
- Accuracy. Hand-written documentation provides opportunities for handwriting errors, transcription errors, and formatting errors due to their very nature. There are always issues of accuracy when entering data from a physical form onto an electronic database for storage: sometimes as high as 6.5%.
These errors significantly weaken the power of the study, and can in many cases be powerful enough to prevent it from continuing.
- Security. Keeping physical copies can come with an increased risk of loss, or can make data accessible to people without the appropriate authorization. It can also be harder and more time-consuming to track physical paper trails for auditing.
eCRF clinical trial data solves these problems and comes with even more benefits. Switching to electronic CRF is a faster way of collecting data, removes a huge amount of redundancy, and enables password-protected access across all stakeholders, ensuring nobody can get to data they’re not authorized to view.
On top of all this, it brings boosts to data quality, as it can guarantee the information fed into the system is in the right format for analysis, tracking, and interpretation. This reduces the time needed to clean data for processing and speeds up the analysis as a whole.
These boosts to the quality of data lend themselves to integrating eCRFs with other clinical trial systems such as randomization tools or ePRO apps. Further, these platforms allow for more data to be collected within the same time and financial restraints.
All of this leads to better data, faster submission, and better compliance, and at a reduced cost over the alternative. Essentially, the era of paper CRF has passed, and sites should all be joining the trends toward better data and a more streamlined process. So, there’s a strong case for trials of every scale and complexity switching to electronic versions of their old paperwork to benefit from these advantages.
However, in order to best leverage eCRF in your clinical trials, there are some things to consider. Choosing the right eCRF goes a long way to allowing you to leverage these benefits to your advantage without overspending.
eCRF Clinical Trials: Considerations for Setting Up
If you’re expecting to shift to eCRF, there’s more to consider than simply the perks that come with it. eCRF design is determined by several different aspects that need to be taken into account to fully leverage its benefits in clinical trials.
User-friendliness has to be a top priority. Regardless of the power of the electronic form, if your participants aren’t comfortable using it, you will lose data and decrease engagement. Design elements to put first and foremost are:
- The time it takes to get set up
- Clear navigation
- Appropriately-place help texts
- Minimal free-text entry options
- Language options
This might seem intuitive, but without performing a thorough acceptance testing session or two, you’re going to find that there are unforeseen roadblocks to getting your platform accepted. The only way to avoid the pitfalls of implementation of any system is to investigate deeply the requirements you have, and then try some testing sessions to make sure it does what you want it to do.
So, user experience is a key consideration, but you also have to choose between any number of systems. When looking into which system to pick, the cost is always a concern. You might find that you’re paying for the full year when you only need to collect data once or twice in that period. So, make sure the system you’re paying for has the features you want, as well as:
- Good customer support
- Few unnecessary features
- A capacity to adapt to any study
This last one is important. Almost all studies need to adjust something after being initiated, so adaptability is one of the key features of a reliable system in most cases, and ignoring this capacity when choosing one could result in a lack of flexibility down the line when it’s too late to go back.
As more systems are being created, the scope of an eCRF system seems to be increasing. Other features that might or might not be useful include:
- Built-in Audit Trail systems
- Electronic signature capabilities
- Data export and import in different formats
- Secure change functions that do not interrupt data entry flow
- Integrated randomization processes
- Soft and hard copy generation
- Attachment capacities, such as photos or audio files
- Key indicator tracking and reports
Finally, it’s important to consider not only the ways in which a new eCRF could make your life easier but the ways it might cause some problems, too. There are some disadvantages to eCRF systems, and these all need to be factored into your decision-making process.
Firstly, the acquisition and setup costs are significantly higher than with paperwork. Then, the tech to fit your needs actually needs to be available to do so. Once you’ve paid for it, can anybody use it? You’ll have to factor training costs into the move too.
Ask yourself, is your upcoming study suitable as a candidate for the first-time use of a system like this? New systems might not be a great addition to an already complex trial. Finally, most systems will require internet access to use well, so depending on where your participants are, this could become an issue.
Conclusion
eCRF is undoubtedly an improvement upon its pen-and-paper predecessor but making the switch does require some forethought, and the drawbacks of changing to an electronic data capture system cannot be ignored. Ultimately, as the systems become more ubiquitous in clinical research, many of the benefits will be compounded and the drawbacks diluted as competition arises to provide the best possible service at the most affordable price.
In the meantime, doing your due diligence and finding the system that best suits your needs (and is adaptable enough to change with them) is the best way to leverage this new technology to your advantage.
