Estelle Haenel

	Digital solutions have without a doubt improved both the quality and the quantity of data collected in clinical trials. The positive impact that eClinical Outcome Assessment (eCOA) has had on the success of clinical trials is no longer disputed 

, and this is in addition to increasing preference among end-users for digital data reporting. The annual eCOA adoption growth rate has been reported to be 16%, yet less than 25% of all possible studies incorporate eCOA

, primarily due to misperceptions of the risk factors associated with implementing eCOA and eCOA backup solutions.Contrary to popular belief, e-devices are rarely damaged; they seldom need replacing. And unlike paper, the volume and quality of digital data collection are significantly higher, thereby adding value to the study. Given the wide use of digital technologies in society today, apprehension about implementing eCOA and creating an eCOA back-up plan is unwarranted. Rather, with the choice of eCOA back-up solutions now available, implementing an eCOA back-up plan that safeguards, as well as optimizing data collection, has become a streamlined process readily adaptable to the specifics of any project.

e-device failures are the exception rather than the rule

	Even though cases where e-devices fail are quite rare, significantly limiting the overall risk of losing data, a robust back-up solution remains necessary. eCOA back-up solutions enable clinical sites and sponsors to guard against two types of potential electronic device failures: permanent failure (through theft or breakage); temporary failure (through a connectivity issue, forgotten password, or loose electrical cable, etc.). 

an investigation6into the use of electronic devices (using real data from several studies across multiple therapeutic areas of various duration and complexity, and with different eCOA device models) revealed that e-devices are rarely stolen or broken at sites, with less than two per cent (<2%) of e-devices requiring replacement and more than 90 per cent (>90%) of sites never needing to make a replacement.

In most cases, a back-up solution is only needed temporarily 

when a password is forgotten or when a device runs out of battery. The occurrences of these incidences can be greatly minimized with recurrent training and strong preparation of both the study site and the patients. 

	It is important to approach an eCOA back-up solution as an integral part of the study design and not just as an ‘add-on’ to a clinical trial. Given the wide choice of electronic options now available, and in order to adhere to the recent recommendations from the competent authorities as well as the specialized organizations such as the C-Path Institute PRO and ePRO Consortiums, an efficient back-up solution should not be paper-based. 

Wider choice of eCOA back-up solutions enable a better adapted eCOA backup plan to meet project needs

	It has been well-documented that paper-based approaches result in untimely, unreadable, missing or often illogical data, all of which can have a very deleterious effect on data quality

. It has also been strongly discouraged by the C-Path’s institute ePRO Consortium

to use paper as a back-up solution. “We s

trongly discourage the mixing of paper and electronic field-based instruments and suggest that mixing of only electronic modes be considered for clinical trials and only after equivalence has been established

	Selecting a well-adapted electronic back-up solution can be quite simple as long as it is anticipated and implemented with a well-coordinated project plan. It can be extensively supported by eCOA solution vendors and eCOA experts, and will also be facilitated by detailed review of the four existing options to characterize them and evaluate their advantages and drawbacks:

consists of making sure that, before site initiation, one or several spare devices will be supplied onsite, in accordance to the specifics of each project and the site’s recruitment projections. The spare device is an easy and frequently used backup solution, but implies additional budget that is to be considered upfront.

The provision of a spare device at the country level 

where another device can be provided quickly, either by an eCOA provider support or by another local site that has spare devices. This solution is similar to having spare devices onsite, but requires preparation, such as anticipating potential shipment delays, that are to be considered upfront of the study. This option tends to incur delays and may not work everywhere; however it remains a cheaper back-up option than maintaining spare devices on each site and so may be the preferred option should the budget influence eCOA backup solution choices.

The availability of a web portal data entry

that could be accessible on the site, as well as on the premises of patients’ homes, so that patients can complete their ePROs and e-diaries in a user-friendly environment. This solution does not add cost or complexity to a trial. It can more readily deployed in most countries now, given the expanded access to computers and the internet. However, developing alternative solutions will still be required to address the needs of patients without access to a home computer.

patient’s own personal device in a BYOD manner 

can be a very convenient and well-adapted back-up solution. The convenience for patients using their own devices can be significant: 

		It eliminates the learning curve to use a new device

		It removes the need to keep track of an additional device

		It increases a level of comfort by not having to collect or return a provisioned device to the site.

	However, deployment of this type of solution does not come without the technical challenge of ensuring that the solution will work in a standard manner on different types of devices-should several patients request this solution. It could also increase the burden for the site’s staff, having to verify the upload of the application and access to the patient’s questionnaires or e-diaries. It can be a fair reason for a team opting out of this option.

	There now seems to be sufficient eCOA backup solutions available for each clinical team to find a tailored plan that will satisfy the requirements for each project and therefore secure patient and clinical data collection.

An eCOA backup solution has to remain a temporary solution

	It is important to note that back-up solutions should only be deployed in the specific circumstances. This is where the original designed solution cannot be used because of device failure, loss or impossibility of use, and is a temporary solution. The timeframe should be limited, and it should never replace the original solution. 

	Using a back-up solution-as an alternative data capture for a significant period of time-would lead to significant “mix mode” of patients’ data capture which may complicate the audit trails, lead to potential lack of comparability of the data and so may potentially jeopardize the validity of the clinical trial. The FDA states in their PRO Guidance, that they “i

ntend to review the comparability of data obtained when using multiple data collection methods or administration modes within a single clinical trial to determine whether the treatment effect varies by methods or modes.”

(FDA, 2009). Although technology makes mixed modes of data collection feasible operationally, clinical trial designs need to consider the sources of error variance in the PRO data, and only sufficiently tested PRO collection modes should be considered.

Precautionary steps can help simplify the implementation of an eCOA back-up plan 

	To implement the right eCOA back-up plan requires taking a few well thought through steps:  

: the manner in which patients adapt to the back-up plan will very much depend on their health condition and age. Age is less of a barrier to eCOA primary and back-up solutions now as people’s familiarity with mobile device technologies, including the elderly, has increased. Thus, evidence shows that they can be integrated into elderly patients’ lives more seamlessly

, as long as precautions are taken. Well-designed and customized training, and well-trained 24/7 available multi-language support teams may likely provide the adequate resources and support to the patients for them to accept the electronic back-up strategy more easily. 
		 

geographical characteristics of your study

: on top of the characteristics of the patient population, the eCOA technology implementation and the back-up solution should consider the locality and the prevalence of technology used in each geographical location to determine the modality and specification of the provisioned devices, as well as the optimum back-up strategy.
		 

: align the level of investment of your back-up plan to the purpose of the data that is being collected: is it for a primary or secondary endpoint? Is the data critical for efficacy or safety assessment that it will justify 100% of data should necessarily be collected? 
		 

primary question of your protocol and goal of your research in selecting a back-up plan

: you may not need the same type of back-up solution should your study be an efficacy and safety registration study, or an epidemiology research. The analysis conducted upfront of the study start will positively impact the decision on the back-up solution to develop. 
		 

Consider the operational aspects of your trial: 

the clinical site organization and the site’s staff experience will also influence your choice. Sites with decades of expertise in clinical trials and experience with using digital solutions will likely be at ease at adopting any back-up strategy, whilst less experienced sites may need the simplest solution. Also, the skillset of the site’s staff, the infrastructure of the hospital are parameters to be considered before developing your back-up plan.
		 

what is the eCOA data being collected for? Who is the patient population? Where is the study being conducted? How are the patients visiting the sites? How likely is the site staff to control deployment of the eCOA solution on site?… All these are questions that, when answered, will facilitate the eCOA back up strategy selection and implementation.

Apprehension about digital technologies seems unÂ­Â­Â­Â­Â­warranted. Continued education of all parties, shared experience and learnings of clinical trial stakeholders, and reference to existing regulations and recommendations from the authorities do represent a strong avenue to support eCOA implementation and electronic back-up solution strategies. 

Implementing a complete eCOA strategy, including an adapted backup solution, creates a way to support both the industry stakeholders in their collection of clinical data, and the patients and the sites who generously provide them. 

Coons SJ et al.: Capturing Patient-Reported Outcome (PRO) Data Electronically: The Past, Present, and Promise of ePRO Measurement in Clinical Trials. Patient 2015, 8:301–309

https://www.ncbi.nlm.nih.gov/pubmed/25300613

Dale O, Hagen KB. Despite technical problems personal digital assistants outperform pen and paper when collecting patient diary data. J Clin Epidemiol. 2007, 60:8–17.

https://www.ncbi.nlm.nih.gov/pubmed/17161749

Yeomans A. The future of ePRO platforms. Appl Clin Trials 2014. 

www.appliedclinicaltrialsonline.com/appliedclinicaltrials/article/articleDetail.jsp?id=833920&pageID=1

Outcomes in Focus:  Best Practices for eCOA. Applied Clinical Trials 2018

http://www.appliedclinicaltrialsonline.com/outcomes-focus-best-practices-ecoa


		https://c-path.org/wp-content/uploads/2018/05/2018_Session3-eCOA_FINAL.pdf 	

White Paper “Challenges of back-up solutions in eCOA studies” by Kayentis 

https://kayentis.com/challenges-of-back-up-solutions-in-ecoa-studies/

Data quality and power in clinical trials: a comparison of ePRO and paper in a randomized trial

https://www.taylorfrancis.com/books/e/9781315580142/chapters/10.4324/9781315580142-10

Coons SJ.: ePRO Systems Providers: Clearly Defining the roles of Clinical Trial Teams and ePRO System Providers, ISPOR 2013, 16, Issue 4, Pages 457–458

https://doi.org/10.1016/j.jval.2013.04.006

Eremenco et al. PRO Data Collection in Clinical Trials Using Mixed Modes: Report of the ISPOR PRO Mixed Modes Good Research Practices Task Force.  Value in Health 2014, 17: 501-516

Watson C.: Mobile, the Future of Patient Reported Outcomes. Appl Clin Trials 2015.

http://www.appliedclinicaltrialsonline.com/mobile-future-patient-reported-outcomes

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Given the wide use of digital technologies in society today, apprehension about implementing eCOA and creating an eCOA back-up plan is unwarranted.

Estelle Haenel

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