Clinical Outcomes Assessments (COAs) in Clinical Trials: Copyright and Licensing

Author: Maria Arnott and Corinne Shoch, COA/eCOA Licensing Management Team

In clinical trials, it is usually necessary for sponsors to obtain permission to use copyrighted materials, such as clinical outcome assessments (COAs). The process to obtain these permissions is called licensing. While a seemingly complex process, it is important to understand why it is necessary, what it consists of, and what needs to be done to ensure that the sponsor is complying with all the necessary requirements.

This process may be handled directly by the sponsor, or it can be outsourced to a third party such as the CRO, the eCOA vendor, or the language services provider.

Sponsors should always make sure to follow the proper steps to obtain all necessary permissions for the use of an instrument. Failure to do so may result in copyright infringement, culminating in monetary repercussions, jeopardized reputation of the offending individual/entity, and/or a detrimental impact on the clinical trial/study. Sponsors should always obtain permission to use copyrighted instruments before the start of the clinical trial.

What Is Copyright, and How Does It Affect COAs in Clinical Trials?

The FDA defines COAs as “measures that describe or reflect how a patient feels, functions, or survives.” These measures are usually presented in the form of questionnaires, assessments, or diaries. There are four types of COAs depending on who completes these measures: patient-reported outcome (PRO), clinician-reported outcome (ClinRO), observer-reported outcome (ObsRO), and performance outcome (PerfO). Sponsors commonly use these measures to assess the patient's experience with their condition as one of the most important sources for data collection in clinical trials.

Copyright is a legal means of protecting an author’s work. It is a type of intellectual property (IP) that provides exclusive publication, distribution, and usage rights for the owner. Many different types of content can be protected by copyright. The IP dealt with in clinical trials are COAs.

One of the ways for copyright owners to protect their work (COAs) is through licensing. A copyright license provides authorization to a licensee to use a copyright owner’s COA, usually in exchange for payment. This is the most common situation in the scope of clinical trials. In the cases where a COA is protected by copyright, the sponsor of the clinical trial will need to request a license from the copyright holder to obtain permission to use the copyrighted COA in a clinical trial. This permission or license is usually granted in the form of a licensing agreement.

Licensing Agreement: What Is It, and What Does It Cover?

A licensing agreement is a contract between two parties (the licensor and the licensee) that grants the licensee (usually the sponsor) the ability to use IP (the copyrighted COA) owned by the licensor (developer or copyright holder). In this agreement, we find all the general terms and conditions to use the copyrighted COA in a study or clinical trial.

This agreement covers the permissions granted to the sponsor and establishes the conditions of use—to be met by both the licensor and the licensee—as well as any restrictions on the use of the instrument. For example, it stipulates which clinical trial the COA may be used for, dates of use, the language versions to be used/developed, and/or the number of patients and administrations. It should be noted that normally a separate licensing agreement is required for each clinical trial.

Permissions granted in licensing agreements cover the use of the COA(s), which specific COA(s) and what language versions will be used, whether the licensee has permission to translate the COA(s) or to modify them should they require additional language versions, associated fees, and the specific terms and conditions of use. The agreement also includes information about the study and the sponsor. Fees for the use and distribution of a COA are established by the licensor.

Permissions to translate 

Regarding translation permissions, these allow the sponsor to develop a non-available translation by a vendor of their choice. Most licensors require that translations undergo linguistic validation and/or have specific translation guidelines to follow, so this should be checked directly with the licensor. Once the language services provider has completed the required translations, they are normally reviewed by the licensor, and they become the licensor’s IP upon approval and completion. 

The license holder will provide the sponsor with any existing translations they hold for which permission to use has been granted. These are usually available with corresponding certificates of translation (CoTs), verifying that the COA has been accurately translated into the target language following the translation procedure required by the licensor. CoTs are not always provided or available, so it is advisable to check with the licensor in advance should the sponsor require these for submission purposes. 

In many cases, the licensor/copyright holder is directly involved in the translation process and will request to review the translations developed by language services providers for approval. They may also require a review of the screenshots for the eCOA versions. Translation requirements and guidelines should be verified with the licensor/copyright holder at the start of the process to be sure that the correct procedure is followed.

Some licensors use universal language versions, meaning they will have one language version to be used in all countries where the language is spoken, rather than different country-specific versions. They may or may not allow for translation adaptations. In these cases, it is best to consult the licensor directly to ensure that universal language versions can be used in specific contexts.

Some copyright holders use the help of third parties to handle the distribution of their translations. There are many of these distributors in the industry, and they need to be contacted to obtain the translations, for which fees will apply. Sometimes, these distributors also handle the licensing and permissions on behalf of the copyright holder.

Permissions to modify

Should the sponsor wish to modify or adapt the instrument to the specific needs of their study/clinical trial, they must obtain permission. If the licensor agrees, this would be included as part of the permissions granted in the Licensing Agreement. This can include translating instruments into additional language versions, modifying the wording/content, etc. This must always be agreed upon with the licensor and explicitly stated in the Licensing Agreement, and the licensor may require that the modified work be approved prior to use. “Modification” can also include the adaptation of a COA instrument from a paper version to an electronic version. Modifications of an instrument cannot be made without obtaining explicit permission from the licensor. 

Licensing Fees

Licensing fees will vary depending on each COA and licensor. In general, these fees are calculated based on various factors such as the number of patients, administrations, languages, questionnaires/assessments, modes of administration, studies, etc. 

Conversely, fees may be given for annual licensing, unlimited licensing, or as a fixed price agreement (usually for the duration of the study). The most typical of these is the fixed price agreement, with the fee calculation based on the licensor’s parameters and valid for the duration of the study.

Apart from the licensing fee itself, there may be additional fees for any supplemental costs, including required training, manuals, or reference materials, for example. In cases where the licensor has chosen a vendor to translate and distribute their COA(s), additional fees for the translation development, royalty, and/or administration may also apply.

What Information Is Needed to Draft a License Agreement?

When requesting a license for a COA, the licensor will require different types of information to generate the license and calculate fees. Information required to create the licensing agreement typically includes:

• The main information on the instruments to be licensed, such as the instrument name and the version to be used (if applicable), the mode of administration (paper, electronic, or both), the language versions needed in the study (language and country of use), etc.

• The details concerning the clinical trial or study in which the questionnaire will be used, like the study protocol number and title, the number of subjects that will take part in the study, the number of times the COA will be administered, and the therapeutic area. The start and end dates of the study should also be provided. 

• The full contact information of the sponsor and billing information for invoicing purposes.

• In cases where there are third parties involved, the licensor will request the relevant information concerning the clinical research organization (CRO), the COA provider, and the language services provider (if applicable).

Changes after a license has been obtained

If any of the information about the clinical trial/study changes after its commencement and the protocol is updated, the licensor must be notified, as these changes may imply additional fees and/or updates to the licensing agreement. Amendments to the fully executed license agreement may be needed to add or remove information.

Examples of such changes include:

• Addition or removal of language versions

• Addition or removal of instruments

• Change in the number of subjects/patients

• Change in the number of administrations

• Changes in the date(s) of the clinical trial

• Addition or changes to modes of administration (paper, tablet, handheld, laptop)

Common Licensing Challenges

The licensing process can be challenging, as every situation is unique. This is not only because the licensing requirements are specific to each license holder but also because of many other factors that need to be considered concerning the study details and needs. Some of these include:

• Difficulty providing licensing timelines to the licensing requester – There are multiple factors that may cause delays in the process that make it extremely difficult to define licensing timelines.

• Licensor’s lack of responsiveness – Licensors also work as professors, medical practitioners, etc., and so are not always readily available. They may not check their email regularly or may only dedicate certain days/hours each week to matters concerning their instrument. This can make it difficult to predict how long a licensing process will take, as it depends largely on the responsiveness of each licensor.

• Insufficient/inaccurate information provided from the requester concerning the sponsor and the study – If the sponsor fails to provide pertinent information needed to calculate licensing fees, draft the License Agreement, etc., this will cause delays. The information will need to be obtained by going back to the client, waiting for them to provide the missing information, and then going back to the License Holder so that they can continue with the process. In a similar way, should the sponsor provide inaccurate information that needs to be changed or updated (e.g., the number of administrations or the wrong instrument), we would need to revise this information with the Licensor, which would inevitably slow down the process.

• Agreement review timelines from both licensor and licensee – Both the licensor and licensee will need to review the agreements. This can cause delays, as each side must review the agreements, send any edits back for additional review and approval, and then, once both sides agree, send the agreements back and forth for signatures. This process is very difficult to give a concrete timeline for, as it depends largely on individuals and is subject to a myriad of factors that can cause delays.

• Changes to the study/protocol that require updates to the license agreement (please see above Changes after a license has been obtained) – Should information about the study/protocol change, the licensor should be notified. They will need to approve these changes, update the License Agreement and potential fees, and then resend the new Agreement for review and signature. Examples of such changes include the number of administrations, the number of subjects, and the study dates.

• Multiple licensors/copyright holders (situations in which one COA requires permission from multiple copyright holders – Certain COAs have different copyright holders—for example, for different language versions. In these instances, each copyright holder will need to be contacted separately, which implies more individuals involved; more coordination required in terms of agreements, signatures, etc.; and more time needed to obtain all the licenses (the number of licenses requested multiplies depending on the number of languages needed for the study). Another example is the case of separate licenses required for the paper and electronic versions. Sometimes, these two licenses are handled by the same license holder (simply signing the agreements with the sponsor and the eCOA vendor separately). Alternatively, these can be handled by separate license holders—one license for each one of the versions. 

• The licensor does not allow third parties to handle the license (CRO or eCOA vendor) or sign the license agreement on behalf of the sponsor – This situation is commonly found at the beginning of the licensing process. The sponsor contracts a third party to handle the licensing on their behalf, like the CRO or the eCOA/language services provider., but unfortunately, most copyright holders refuse to have the license agreements signed with a third party that is not the sponsor of the study. 

• The licensor develops his own translations or has an exclusive language services provider – In these cases, the licensor does not grant the sponsor permission to translate and charges them for the development of the translation(s) if unavailable. The licensor or the exclusive language services provider also determines the translation deadlines, which may not adjust to the study timelines. 

• Questionnaires in the public domain – These questionnaires are made available by the developer/copyright holder for everyone to use. They do not require licensing and are free of charge. However, some of them are copyrighted, and permission to use them still needs to be requested from the copyright holder. In some cases, the user needs to agree to the terms and conditions that usually forbid any modifications, translations, or adaptations without prior consent from the copyright holder. 

There are occasions where there is no clear information available on whether a questionnaire is copyrighted and requires licensing, or if it is in the public domain. In these cases, extensive research is required to confirm this information. 

Conclusion

Navigating the intricate details of licensing and copyright agreements in COAs is a complex task, presenting possible challenges to multi-licensor coordination or in managing evolving study protocols. This complexity, however, is a necessity, serving as an essential tool to ensure compliance with licensor guidelines, safeguard the interests of all parties, and enforce productive, sensible use of clinical IP assets.

Curious to learn more about the importance of sponsor involvement in upholding licensing agreements and mitigating the challenges of validated instruments? Check out our latest episode of TransPerfect LifeSci Talks, “Licensing Challenges vs. eCOA Vendor Capabilities” here.

If you’d like to learn more about how TransPerfect Life Sciences supports leading organizations when navigating COA licensing, reach out to us today. 

Glossary

• Client: the requestor of licensing services – can be the sponsor, the CRO, or the eCOA vendor. 

• Clinical outcome assessment (COA): a measure that describes or reflects how a patient feels, functions, or survives (FDA).

• Contract research organization (CRO): a company that manages the study and provides support for the sponsor throughout the clinical trial.

• Copyright: a legal means of protecting an author’s work and a type of intellectual property.

• Copyright holder: a person or company who owns any one of the exclusive rights of copyright in a work (copyright ownership is separate from ownership of the work itself).

• eCOA vendor: the vendor chosen by the sponsor who handles the electronic implementation of COAs for use in a clinical trial.

• Instrument: this refers to the questionnaire, scale, tool, measure, COA, patient-reported outcome (PRO), clinician-reported outcome (ClinRO), performance outcome (PerfO), or observer-reported outcome (ObsRO).

• License: a legal permission or authorization granted by the competent authority (copyright holder) to do, use, or own something. A licensor may grant a license under intellectual property laws to authorize the use, sparing the licensee from a claim of copyright infringement brought by the licensor. A license under intellectual property commonly includes several components apart from the grant itself, including a term, territory, renewal provisions, and/or other limitations deemed necessary by the licensor.

• License agreement: a contract between two parties (the licensor and the licensee) that grants the licensee (usually the sponsor) the ability to use intellectual property (in this case the copyrighted COA) owned by the licensor (developer or copyright holder).

• Licensor: the developer or copyright holder of an instrument who grants permission to use the instrument.

• Licensee: the sponsor or third party who obtains permission to use an instrument in their clinical trial.

• Developer: the instrument author and creator of the questionnaire (can be different from the copyright holder).

• Sponsor: the pharmaceutical company conducting a clinical trial.