Considerations for multiple language documentation

A recent issue of Value in Health brought us the long-awaited “Clinician-Reported Outcome Assessments of Treatment Benefit: Report of the ISPOR Clinical Outcome Assessment Emerging Good Practices Task Force”. In this second report of the ISPOR COA GP for Outcomes Research Task Force, the authors focus on issues pertaining to Clinician Reported Outcomes (ClinROs).

ClinROs are a type of Clinical Outcome Assessments (COAs), which are used in clinical trials to measure health status and define end points that can be interpreted as treatment benefits on how a patient feels, functions, or survives. A ClinRO assessment, as its name indicates, is conducted and reported by a trained health care professional; specialized training is required in order to evaluate the patient’s health status.

According to the Task Force Report, a recent study showed that more than one quarter of denials of the first review approval for new drug applications (NDA) submitted to the FDA were based on lack of clarity on the clinical meaningfulness of end points (13.2% of NDAs), and a lack of consistency across multiple study end points (in another 13.2% of applications). This data highlights the importance of good measurement practices and proper development of outcome assessments for use as end points in clinical trials to more efficiently and accurately measure treatment effects1.

The report summarizes the good measurement practices in a checklist, which can be useful during development and evaluation of ClinROs. We have provided an outline in Table 1; the fully defined list can be found in the referenced report.

Going back to the NDA denials mentioned above, it is evident that a clear clinical meaningfulness of end points is key for drug approvals. As stated in the task force report, both clinician and patient input is necessary. “When inadequate attention is given to input from patients, clinicians, regulatory agencies, payers, or sponsors, the concept(s) of interest may be 1) inconsistent with the trial objectives and 2) challenging for interpretation of the clinical trial findings. There may be a lack of empirical evidence that the outcome assessments used as end points actually provided evidence of a meaningful benefit for patients.” ¹

How can TransPerfect help in the initial development process, when identifying the concept(s) of interest? Our wide network of cognitive interviewers and clinicians/healthcare professionals, as well as patient recruiters, allows us to provide the highly-specialized resources to conduct focus groups, concept elicitation interviews, and any other surveys with the purpose of identifying the meaningful aspect of how patients feel, function, or survive that is hypothesized as the intervention’s treatment benefit.

As we go through the checklist for good measurement practices for ClinROs, there is another step where your LSP can assist–documenting content validity. Obtaining clinician input is essential in order to establish the appropriateness and comprehensiveness of the specific ClinRO’s content for measuring a particular concept of interest in a particular context of use.¹

Through either cognitive interviews or clinician reviews by specialized healthcare professionals in the specific therapeutic area of the assessments, we can obtain evidence of content validity. Furthermore, when it comes to multinational clinical trials that involve different languages and countries, it is imperative to assess whether the translated versions convey the same concept as the source document and are consistent in all regions.

Another consideration is evaluating the differences in expertise and training, as well as variations in clinical practice at the different study locations, in order to inform content validity. TransPerfect’s Rater Training team is highly specialized and has global capabilities to help in multinational studies.

Lastly, when thinking about operational considerations for implementation in clinical trials, there are a number of opportunities for collaboration. For example:

• Protocol and rater training standardization
• Comprehensive manuals for administration/rating/scoring
• Consistency between documents and countries

All these materials should be provided in the native language of the sites where the clinicians will be conducting/assessing the measures for the clinical trial. TransPerfect’s Life Sciences and Linguistic Validation groups have resources in place to help in the development and implementation of these highly technical documents, thus ensuring good measurement practices when using ClinROs to assess treatment benefit. This in turn will increase the likelihood of FDA approvals for your new drug applications.
 

ISPOR Good Measurement Practices Checklist for COAs: ClinRO Assessment Development and Evaluation.

• Define context of use
• Choose intended treatment benefits
• Identify concept(s) of interest
• Evaluate the relationship between treatment benefit and concept of interest
• Document content validity
• Evaluate other measurement properties
• Place of ClinRO in defininig end points/objectives – place in hierarchy of end points
• Interpretability of results
• Operational considerations for implementation

¹Clinician-Reported Outcome Assessments of Treatment Benefit: Report of the ISPOR Clinical Outcome Assessment Emerging Good Practices Task Force - Powers, John H. et al. Value in Health , Volume 20 , Issue 1 , 2 - 14