Green EDC?

Besides working in Clinical Trial technologies, I also have an interest in tackling issues around global warming.  Electronic Data Capture in clinical trials has the advantage in that it inherently lends itself towards tackling many of the issues that contribute towards global warming.   I am interested in both the benefits that can be achieved during the implementation cycle, as well as the value during the execution phase.

Green EDC does make a lot of sense from many perspectives.  In almost all instances, working with an electronic medium is considerably faster than working with paper. This leads to a reduction in cycle times, and lower costs. You can basically 'do more with less'.

Using technology today

eLearning

Probably the most obvious one.

Large, expensive Investigator Meetings were common until only a few years ago.  Changes in rules and attitudes have ensured they have become more functional rather than an investigator incentive. As a result, unnecessary travel has been reduced.  However, are investigator meetings actually required?

From the EDC perspective, training is often provided during the course of the meeting.  This can take up as much as half the time spent.

eLearning solutions, available from many of the EDC vendors, should alleviate the need for Investigator meeting training.  At most, you might be looking at a short demonstration. If eLearning is implemented well, it has many advantages over traditional instructor led training.  It should be integrated into the product, it should be integrated into the workflow, and, it should adaptable to meet the changing training requirements from study to study.

Integration is important. The early eLearning solutions were often implemented as separate tools.  You would be provided a separate login to access the eLearning - you almost had to learn to operate the eLearning tool!   With fully integrated eLearning inside EDC, the EDC system login directs trainee through appropriate eLearning topics based on the role they have been assigned to, before they can participate in the study. Participation and test results are all logged ensuring an electronic record is maintained for process compliance.  Another advantage of eLearning is the ability to train new staff prior to Monitoring visits.  In the past, a new study nurse for example had to wait until potentially the Monitors next site visit.  With eLearning, they simply await a login, perform the eLearning and they are ready to participate.

Less Monitoring Visits

Besides the removal of the need for monitors to attend sites regularly for staff training, the overall number of Monitoring visits should be reduced with effective use of EDC systems themselves.  Monitors are increasingly taking the role of the Data Manager in carrying out the duties of data review over and above the cleaning functions of the study build itself.  Source Data Verification remains necessary, but the actual Q & A regarding the data itself can be carried out remotely.  Less Monitoring visits means typically less air-travel.

Less Paper

This seems obvious - we are talking about replacing paper with an electronic medium - however, we also have paper flows in other areas of the process.   The development of the EDC product itself together with the implementation phase of the system for a study often involves the preparation of many binders of paper materials designed to support a vendor (or regulatory) audit.  Despite the electronic nature of the solutions that EDC companies provide, very few companies effectively push a paper development and implementation process.  The use of electronic document management systems are beginning to change this, but, it does require the support of Quality Assurance and Regulatory groups who tend to be more comfortable with a large pile of paper binders and wet ink signatures than fully electronic systems.

Widely used standards for document signatures are currently a barrier.  The SAFE BioPharma Association have had some success in offering up a electronic document signing solution that could be used across the industry, but it still has some challenges related to Hardware and Technology dependency. We may see progress following SAFE's partnership with CDISC.

Paper itself is not that 'non-green', but the delivery of paper can be.  Organizations involved in clinical trials today are often global.  Fedex'ing a CRF, a specification or a submission in paper format is simply not necessary with technology available today.

Messaging and Video Conferencing

Is it not odd that a technology such as video conference has such limited use in business today, and yet teenagers all round the global use it regularly to chat with their friends over the internet? 

Some EDC systems make use of tools to provide interactive support, but they are often poor.

If I am using an Internet application - such as banking or the like, and I have a problem, I would like to chat - by keyboard or over the phone - immediately.  Messenger services either inside, or outside of the EDC application are available today.  I have yet to see a good implementation of interactive support within the tool.  [I am sure EDC vendors that already have such services built in will correct me here!]

By offering interactive support and communication tools within an EDC product, site personnel can achieve equivalent, or potentially better support than can be achieved through infrequent monitoring visits.

 

Tomorrows Technology?

So, what can we still do to improve our green credentials when carrying out clinical trials?

Standards

Applying standards, can improve overall efficiencies.

Since 2004, SDTM, the Submission Data Tabulation Model from CDISC is part of a move to a standard electronic medium for data submissions.  The electronic submission of course is not new, but the standardization of the format is new making it somewhat easier for regulatory bodies to process data received regardless of the source.  Standard outputs require standard inputs, so with the recent introduction of CDASH - Clinical Data Acquisition Standards Harmonization- a standardization of the input structures in clinical trials - the overall SDTM production process should become less onerous. 

Downstream from EDC, we have the eCTD - electronic Common Technical Document an interface for the pharmaceutical industry to agency transfer of regulatory information.  From 1/1/2008, this is a required format (barring a waiver) by the FDA and has/will result in a great reduction in the amount of paper delivered to regulatory authorities.

Trial Execution Efficiency

Both Adaptive Clinical trials as well as non adaptive studies where a Bayesian continual reassessment method (CRM) is taken, can help ensure that unnecessary trial execution work is avoided.  In the past, trials tended to be more serial in nature - complete study A before moving onto Study B.  With the ability to adjust the design, and, more commonly, the ability to examine data subsets early in the trial, either an early termination or a change of focus can be made saving time, money and of course our impact on the environment.

Source Data Verification

Going back to my eBanking analogy, if I want to record a payment transaction into my eBanking solution, I do not write it down on paper first, and then transcribe what I write down into the eBanking transaction form. There is no value in that.

In clinical trials, if an investigator is involved in a clinical trial where the subject responds to questions during data entry, it would make sense to in certain circumstances to enter these directly into the EDC system, and not on paper first  - as source date - this would avoid potential transcription errors. 

But no....The interpretation of guidelines regarding Source Data typically means that web based systems cannot be used to retain the 'Source Data'.  I personally have an issue with this interpretation, but I will not elaborate here.  It is indicated that the 'Source Data' must remain at the site. Web based systems do not hold data onsite, but instead hold the data on a central server.  [Dave Iberson-Hirst from CDISC provided a good description of the challenges of Source data in his article in Applied Clinical Trials focusing on electronic Patient Diaries - for the sake of brevity, I have summarized the points of argument.]

Workarounds have involved the use of an offline, or hybrid system where the data is stored on a local device at the site.  More commonly though, data is recorded on paper first, and then transcribed into the electronic CRF.  Admittedly, a lot of source data will come from Medical records, and other paper records, however, it seems rather regressive that due to the wording of a regulation, more data is captured on paper first for web based systems that the old fashion Remote Data Entry tools.  Hopefully improved guidance in the near future will avoid this.

Conclusion

I am a great believer that being 'Green' means being efficient in business. Reducing the inefficiencies in how we go about our work not only offers savings in time and money, it can also have a positive impact on our environment. Here's to an electronic clinical world!

Top 10 mistakes made when implementing EDC

(last update from admin @ eclinicalopinion)

Ok, I am calling for a challenge here.  I am making an attempt at identifying 10 top mistakes that I believe are made when companies attempt to implement EDC.  No science to this. Just a bit of fun.

I will make edits if anyone posts comments that I believe out do my own;

 

1. Pick the nastiest, most complex study to implement as a first study

Sponsors may be trying to check the EDC system and vendor as a confirmation of claims of functionality, services and support.  It may also be an internal organizations 'sell' when bringing in a new system. In reality, the risk factors are at their highest, and the chances of failure greater than at any subsequent time in an Enterprise EDC system rollout.  Instead of learning and improving with optimized processes and a well designed workflow model, a 'get it out the door quickly' approach is forced and pain is suffered from all parties!

2. Expecting the return on EDC to be immediate - admin @ eclinicalopinion

Many clients are very experienced with paper and have wrung the very last drop of efficiency out of their process. They start with EDC believing that they are entering a new golden era only to be disappointed with the gains (or losses!) on their first study.
As with any new process or technology, it takes time to refine. The potential gains are real but it will take a few trials before a company hits its stride with EDC.

3. Over emphasis on faster closeout- admin @ eclinicalopinion

Companies new to EDC getting excited about the faster closeout of EDC trials but ignoring the issue of longer start-up times with EDC. With paper you could print the CRF's and send them out before you have finalized (or even built) the database that will finally store the data.

4. Use all the functionality that was demonstrated

A common problem. When a sales person demo's the product, it looks cool. Almost every feature looks good, and could add value.... Well, in reality, not always.  Many EDC systems developed today offer features as a 'tick in the box', but when the feature is used and combined with other features, sometimes the value falls short.  For example, most systems offer some form of data flagging... Reviewed, SDV'd, Frozen, Locked etc etc. Do not use all flags on all fields.  That will be slower than paper.

5. Resource the same way

If you have the same resourcing for Data Management and Monitoring AND you are also resourcing separately for building and testing EDC studies - then you have done something wrong.

With a good EDC product, the rules that would typically be applied manually are applied automatically. The delta should be picked up by a smaller number of 'eyes'.  Many CRO's have played the 'better safe than sorry' card to charge for the same Monitoring and Data Management as paper as well as EDC license and deployment costs.  This demonstrates an inexperienced CRO.

6. Model the eCRF according to the paper CRF Layout

Trying to make an electronic CRF identical to an original paper CRF will result in tears.  The users will be frustrated with the workflow.  The 'e' nature of the medium will not be utilized and the study will be less effective.

Instead, consider appropriate workflow and dynamic eCRF's.  I will stress 'appropriate'. Overdoing the bells and whistles can cause frustration, but, no bells and whistles and many of the advantages of EDC are lost.

7. eCRF Design by committee

The surest way to blown budgets and timelines is to attempt to develop an eCRF based on a committee of individuals.  The sponsor should delegate a chosen few (ideally 1) to work with the EDC CRF Designer. The study should be built to a greater %, then following this period, a wider review should be carried out.

8. Wait until the end of the study to look at the Data

It is surprising how often this is still the case. EDC means cleaner data faster, but often sponsors, and their Statistical departments are geared towards working with final data-sets. Good EDC systems can deliver clean data on a continuous basis.  Whether the data is able to achieve a statistically significant sample size is another question, but, information is often available for companies that are willing to leverage it.

9. Fail to use the built in communication tools provided

Many EDC systems offer the means for different parties involved in the execution to communicate.  These might be in the form of Post it Notes, Query Messages or internal email. Often these facilities are either not used, or not used effectively.  This means that the true status of study is a combination of information in the EDC tool, tasks in Outlook, actions in emails, scribbled notes on a Monitors pad etc etc.

10. Do lots of programming for a study

This covers many areas. It could be programming to handle complicated validation rules, or it could be programming to adapt data-sets to meet requirements. If you're EDC system requires lots of programming in order to define an EDC study, then I would suspect you have the wrong EDC system. Good EDC systems today are configured based on metadata stored in tables. Old systems relied on heavy customization of the core code for each deployment, or, relied on some form of programming in order to complete the study build. If you write code, then you need to test it. The testing is similar to software validation.  This takes time and money. 

Most EDC tools can be extended through 'programming'. If you need to do this, try to do the work outside of the critical path of a study.  Develop an interface, test and dry run it, and then, utilize it in a live study. In this way, you will have time to do it right with proper documentation, support and processes.

and relegated below the top 10...

11. Start by developing Library Standards from Day 1

This may sound like an odd one, but, let me explain.  Implementing EDC effectively with an EDC system, even with a highly experienced vendor, takes time.  All parties are learning, and, modern EDC systems take a while to adapt. Workflow, system settings and integrations all need to come up to speed and be optimized before standards can really be applied and add value. Start too early, and the library standards are just throw aways once the teams come up to speed. It is best to leverage the knowledge and skills of the CRO or Vendor first.

12. Develop your Data Extracts after First Patient In

Sometimes tempting due to tight timelines, but, if you have an EDC tool that requires either programming or mapping of data to reach the target format, then the less consideration you give to the outputs when you design the study, the harder it can be to meet the these requirements after FPI. This leads to higher costs, and, the potential for post deployment changes if you discover something is missing.

Conclusion

Many thanks to admin @ eclinicalopinion for the additional 2 mistakes made, now coming in at numbers 2 & 3!  More comments welcome...