Persistent delays and inefficiencies in COA licensing and translation stem from limited pre-license access and fragmented processes, making a strong case for providing outcome assessment measures earlier to reduce risk and accelerate trial start-up.
Instrument: A means to capture data (i.e., a questionnaire) plus all the information and documentation that supports its use. Generally, that includes clearly defined methods and instructions for administration or responding, a standard format for data collection, and well documented methods for scoring, analysis, and interpretation of results in the target patient population.
*in this article, COA is used synonymously with questionnaire
The licensing and translations process for clinical outcome assessment (COA) measures is notorious for being a major pain point in clinical trial set-up, and is often a significant resource burden, from both a time and cost perspective. But this is not a new concern—as an industry, we have been talking for decades about how much of a source of friction this process can be.
All stakeholders—copyright holders, sponsors, CROs, eCOA providers—should strongly endorse the importance of removing barriers in the drug development process and getting treatments to patients faster. So, why are we still encountering the same issues, and what roadblocks (or incentives) are driving the unacceptable status quo and how can they be solved?
The following details common problems encountered during the licensing process that present a risk to study go-live, along with proposed solutions. Furthermore, when—as it so often is—eCOA set-up and implementation is on the critical path to first patient in (FPI) (See Figure 1), these issues can be exacerbated.
Identification of copyright ownership of a COA can sometimes be challenging; research to ascertain this can take time, often requiring contact to be made with several entities, or a trawl through the literature.
Solution: At COA conception (such as during the funding process), developers should ensure a clearly documented path to its use, detailing agreed arrangements for its long-term management—including who will own the copyright, its licensing process, and user support. This is especially pertinent in cases of academically developed measures, where contact information is often only included in a publication, which can become out-of-date if the author has changed institution or retired. Journals that publish findings from COA development should also ensure that clear information on how to obtain permission (if any) for the COA(s) use are available.
Some copyright holders take weeks to respond to a license request and require much chasing throughout the process.
Solution: Copyright holders should have a duty of care to provide clearly stated response times, ideally along with a clear description of the process required to secure permissions for the COA(s) use (e.g., on their website, or via an automated email response detailing this). When considering the appropriate timeline for response, being cognizant of the fact that COA licensing and eCOA implementation is often on the critical path to FPI, is encouraged. More detailed information would also likely reduce the number of enquires received. If a COA developer does not have the resource or expertise to manage this activity, engaging a COA management organization is recommended.
Certain COAs have additional materials that can be licensed (which are not included as standard), and the availability of such materials is not always made clear from the outset. It would be fair to assume that the license would include access to all the available support documentation under the FDAs definition of an instrument1 (Box 1); however, this is not always the case. Furthermore, the cost and timeline implications associated with licensing these elements are not always made clear upfront and can lead to delays and unforeseen (hidden) costs.
Solution: Copyright holders should provide clear information upfront on exactly what a standard license includes and available additions, to enable informed decisions about buying their products. Provision of a minimal package as standard is encouraged, in line with the FDA’s definition of an instrument,1 including:
Additional elements to facilitate electronic implementation may include:
Standardization and consistency in COA pricing models are lacking and can be based on a range of parameters, such as number of sites, participants, administrations, or trial length. As some of these parameters may not be finalized at the point of license initiation (e.g., site selection is ongoing, regulatory bodies may not have approved the protocol), the process can be delayed or will require subsequent license amendments, which is an additional administrative task and potential cost.
Solution: Clear upfront information from copyright holders about pricing parameters for a given COA so licensees can confidently forecast potential licensing costs.
Licenses of copyright are legally binding contracts that can require review from several different stakeholders (including the CRO, sponsor, eCOA provider, and/or training provider) which can take time. Further, when a study is going to use eCOA, some copyright holders require that this is specified when requesting the license and included in the agreement. When eCOA provider selection is on the critical path to FPI, this can delay licensing initiation and execution.
Solution: In the absence of a standard licensing template used by all copyright holders, at the very least, a commitment to turn around reviews in a specific time is needed.
Often, a copy of the COA is not provided until license execution and payment. Not having access to an official copy of the COA prior to this can negatively impact:
Ultimately, it runs the risk that some may obtain a copy of the COA from an unreliable (non-official, possibly adulterated) source, to try and assess the suitability of the COA and meet eCOA build timelines.
Solution: Providing an official copy of the COA (including watermarked sample copy or if developed electronically, access to the items) prior to the execution of the license and payment, would significantly benefit the clinical trial set-up process, and reduce the impact of many of the detailed issues. It would be on the strict understanding that it should not be used in a live study until license execution and payment. The license, in this scenario, is for the actual use of the COA (i.e., for completion within a study). With most things in life that we buy, we can review and assess it prior to purchase—whereas what we see for COA licensing is often buying blind.
Alternatively, a limited rights license (that is quick to execute) could be provided to allow for review and/or eCOA build, enabling eCOA providers to reproduce the COA electronically and make reasonable preparations for study use.
If sponsors request screenshots for ethics committee (EC) and/or Institutional Review Board (IRB) submissions (though they are not necessarily required),3,4 this can create a huge challenge and pressure on eCOA providers to generate these in the time required; especially when the COA is not provided until license execution and payment.
Solution: A clear public statement from IRBs/ECs that eCOA screenshots are not required and the paper COA is sufficient.
Another challenge faced during licensing is the associated translation activities, which present differently dependent on if the required translations already exist or not. For example, it is not always clear what translations are available, the methodology employed (leading to a lack of confidence in faithful translation), and so translations are often repeated, which can lead to variation and confusion.
Copyright holders (or a delegated management organization) should have a duty of care to maintain a published translation database with this information (e.g., on a website)—that is recognized as the only source of official translations—with updates as new ones are added, and on details on access.
If the copyright holder requires approval of eCOA screenshots for every language implemented in a study this takes a significant amount of time, and is a major risk if a sponsor wishes to go live in languages other than a routinely used language (e.g., US English). Copyright holders are encouraged to be mindful of this when requiring approval of all translated eCOA reproductions, or at least sensitive to their impact on timelines when working with stakeholders such as sponsors, eCOA providers and or language service providers.
In short, no. At least not based on the current model, and until there is a more cost-effective model for libraries, they are unlikely to have the utility they promise.
Licensing and translations fees are either paid directly, or are passthrough costs, by the sponsor. In the current library model, the eCOA provider must pay the library license fee. For smaller organizations, and especially when projected use can be unclear (i.e., there is no guarantee of recuperation)—it is risky to front-up what can be a substantial amount of money—sometimes in the millions.
Further, sponsors are still required to pay the licensing fee for the actual use of the COA in a study, so the eCOA provider also must develop a costing model that recoups the upfront cost of the library license, which can be especially challenging where sponsors expect cost savings/reductions from using COAs from the eCOA providers library. Sponsors often very reasonably question that if the eCOA is already built, why should they pay the same price for it again. The library model also saves the copyright holder time and resource as they are not repeatedly reviewing screenshots, and yet they are charging extra for a library license, which as mentioned can be substantial.
An alternative model sees approval obtained by the eCOA provider for their build, and then the copyright holder being notified of a new study wanting to use it, so they can confirm it is the approved build. They would still receive the same licensing fees from the sponsor and not have to review implementations repeatedly.
The challenges outlined are well understood, not insurmountable, and entirely solvable. The current approach and relationship between eCOA providers, copyright holders, and sponsors/CROs remains overly transactional, and it is time to move beyond inertia and adopt practical, collective solutions. A committed effort from all stakeholders is required to address the aspects within their control, and the efficiencies to be gained from relatively simple changes to the processes implemented by many copyright holders are not insignificant by any means. Additionally, sponsors engaging copyright holders and eCOA providers earlier (and off the critical path to FPI) would also mitigate some of the challenges described. By doing so, we can move past these recurring problems and focus our energy on more meaningful goals, such as truly optimizing the user experience of digital technologies and speeding up drug development.
Copyright holders who have adopted many of the solutions outlined above, demonstrate a genuine intention and commitment to find ways to remove delays in getting effective treatments to those in need whilst rightly protecting their intellectual property and the integrity of the COA. Mitigating against improper use of COAs that could bring into question the integrity of the specific use of the COA is critical, and the solutions outlined in this article would not bring that into question The payment and contractual requirements would still be adhered to, and the burden felt by sponsors, CROs, and eCOA providers, would be greatly reduced.
Florence Mowlem, PhD
Acknowledgements: David Churchman, Scottie Kern, and Paul O’Donohoe for their insights
1. U.S. Food and Drug Administration. Guidance for Industry Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims. (2009).
2. Mowlem, F. D. et al. Best Practices for the Electronic Implementation and Migration of Patient-Reported Outcome Measures. Value in Health 27, 79–94 (2024).
3. Gertel, A. et al. Demystifying Submissions of eCOA Documentation for Ethics Review: Are We Making Submissions More Difficult than Necessary? Appl Clin Trials (2020).
4. Riddle, J. Unpacking IRB Innovations for Decentralized Clinical Trials.
