As the healthcare industry continues to evolve, so has the emphasis on prioritizing and capturing the patient experience. While regulators, payers, and providers have historically operated independently, these entities are becoming far more collaborative in their efforts to provide optimal care to patients. Given that patients invest valuable time and energy into sharing their experiences within the context of clinical trials, the success of these trials relies heavily on adequate planning to address patient burden.   
 
This transformational shift in healthcare has driven the widespread adoption of electronic clinical outcome assessments (eCOAs). In implementing COAs electronically, stakeholders are able to capture the patient voice more reliably and accurately, while also complying with regulatory requirements and easing patient burden. But while the increased adoption of eCOAs has established patient centricity as a key priority in clinical trial designs today, an eCOA solution can only be as robust as the scientific strategy it is built upon. Marrying scientific strategy with eCOA implementation is key to building a successful study and minimizing patient burden.

Regulatory requirements for endpoints and instrument selection are rigorous
Regulators have set a high bar for COAs, especially when they are being used to support an endpoint associated with labeling. The challenge many face in selecting COAs is that for labeling, an endpoint must evaluate discreate disease symptoms, but many established patient reported outcomes (PRO) instruments combine symptom and symptom impact items in scoring and are not acceptable to regulators. The 2009 PRO guidance also places intense scrutiny on the instrument selected to evaluate these endpoints, stating that instruments selected for labelling must be fit for purpose in the context of use and demonstrate evidence of validity and reliability. 

COA selection best practices and considerations
With these requirements in mind, there are several best practices to ensure regulatory expectations are met. A successful strategy will utilize COAs that measure concepts relevant to the endpoints that they are intended to support. When selecting COAs, stakeholders should begin by identifying the most salient concepts of the disease (signs, symptoms, impacts, treatment satisfaction, etc.) that are relevant to the selected endpoints. This information along with any published guidelines from regulators and payers in the disease area can help determine which COAs to include in the strategy to adequately measure these concepts of interest, including existing COAs. Sponsors may consider developing a new COA when there is not an existing COA relevant to a selected endpoint. 

Another key consideration when selecting COAs is patient burden. Stakeholders should consider the following questions: 
·       Are there too many questions asked of the patient? 
·       Are the questions valuable and relevant to patients? 
·       Is there overlap between questions? 
·       Are lengthy responses required? 

Of these considerations, both perceived irrelevance of PRO measures and lack of value to patients have been identified as significant barriers to participation reported by researchers. Thus, a successful COA strategy will include PROs that minimize repetition, prioritize ease of completion, and most importantly ensure that only relevant questions addressing the goals of the study are included. 

Translating a COA strategy to an eCOA strategy
The likelihood of endpoint success can be greatly increased by capturing COAs through an electronic implementation (eCOAs). One of the biggest challenges in implementing an eCOA strategy is that there is often a gap when mapping the COA strategy outlined in the protocol to a technical eCOA solution. When the requirements laid out in the protocol are not properly translated into the eCOA implementation or mapping is misinterpreted by the eCOA vendor, there can be detrimental effects on the protocol measurement strategy and possibly the endpoint analysis. Thus, it is crucial that the clinical study team is able to provide feedback and answer the eCOA vendor’s protocol questions impacting the eCOA solution design. The best way to avoid delays and ensure success throughout the design phase is to have knowledgeable study team experts overseeing the eCOA implementation process and to work with a reputable eCOA vendor that has capabilities to provide early visibility and full transparency into the eCOA solution throughout the design and build phase of the implementation. Additionally, there are several prerequisites that should be carefully evaluated before moving forward with an eCOA implementation that will help minimize gaps in mapping a COA strategy to an electronic solution.

Stable Protocol 
A stable protocol includes a well-defined COA measurement strategy, a clear depiction of the relationship between COAs and study objectives/endpoints, and a well-defined study flow that shows what COAs will be captured and when, as well as impact on inclusion/exclusion criteria. 

Ensuring a faithful migration from paper to electronic
To withstand regulatory rigor, an eCOA vendor should always confirm that paper PROs are migrated to electronic formats in accordance with paper to electronic best practices. A faithful migration ensures that when an existing PRO migrates to an alternative form of data collection (such as paper to electronic), the PRO’s original qualities are maintained and any bias resulting from differences in presentation is eliminated. Participants should be able to interpret and respond to the PRO in the same way, regardless of the mode of administration. If the PRO is especially complex or if it will be leveraged in a regulatory context, additional testing and evidence of equivalency will likely be needed. It should also be noted that the proper channels should be followed when migrating a copyrighted paper assessment to an electronic format. It is critical that the appropriate licenses are obtained to utilize the assessment electronically and the copyright holders/owner’s conditions of us are abided by.

The Future is Digital
Technology is the key to clinical innovation. As the healthcare industry continues to recognize the benefits of eCOAs, it is critical that all stakeholders understand how to successfully harmonize science and technology throughout the clinical trial design process. In establishing successful eCOA implementations, stakeholders will simplify regulatory compliance, ensure the patient voice is captured accurately, reduce patient burden, and ultimately drive innovation for life-saving breakthrough therapies.