Applied Clinical Trials
Combining PRO data with clinical feasibility data can make a difference in diabetes care.
Patient-reported outcome (PRO) questionnaires can be used to collect subjective clinical and psychosocial outcome data directly from patients in clinical trials, in order to describe their perception of a disease and its treatment(s), without the interpretation of responses by a physician or others. They are the only systematic quantitative way to ask patients directly about how they feel or function.
In looking at the newer classes of drugs for type 2 diabetes mellitus (T2DM), such as DPP-4 inhibitors, GLP-1 receptor analogues, novel insulins, and SGLT-2 inhibitors, PRO questionnaires have been used to
inform endpoints in most of the pivotal programs. As with the concept of blood glucose, a PRO can contain many related but distinct concepts, including symptoms of diabetes, side-effects of treatment, health-related quality of life, psychological well-being, and treatment satisfaction. Each concept captures a different aspect of a person’s experiences, thoughts, and feelings about T2DM and/or its treatment. All of these have been measured as endpoints across the pivotal trials of the newer classes of T2DM drugs.
This PRO data has the potential to offer insights into the subjective experience of therapy and provide an informed perspective of the associated patient-perceived benefit-to-risk ratio of the medication. Historically, PRO data has not been held in high esteem in T2DM, partly due to the traditional glucose-centric model of care, and partly due to variable scientific credibility in their measurement and lack of clarity in their interpretation.
However, in recent years the science of PROs has progressed considerably, with U.S. and European regulators releasing guidance clarifying their expectations of the scientific rigor that should be applied to the development and selection of PRO endpoints. A recent PRO extension to the CONSORT statement highlights that well-developed PRO instruments can provide reliable and valid data in a manner which is meaningful to clinicians and patients alike. Despite this, the only PRO data to be reflected in product labelling for any anti-hyperglycemic medication for T2DM is blood glucose (based on patient self-recording of objective data). That was, until the 2014 European approval of Trulicity (dulaglutide).
In the efficacy and safety section of the summary of product characteristics for Trulicity, the European Medicines Agency (EMA) included the following text: “Dulaglutide significantly improved total treatment satisfaction compared to exenatide twice daily. In addition, there was significantly lower perceived frequency of hyperglycaemia and hypoglycaemia compared to exenatide twice daily.”
Demonstrating improvements from baseline in treatment satisfaction with Trulicity, and showing that this improvement was greater with Trulicity when compared to exenatide twice daily, allows the developer of Trulicity (Eli Lilly & Co.) to summarize with one metric the patient’s appraisal of his or her experience with treatment (i.e., both processes and outcomes), their perception of the relative balance between positive clinical outcomes and negative side-effects, and their perceived benefit of improved clinical efficacy and reduced injection frequency versus an efficacious comparator. Perhaps most importantly for translational researchers, the data is important for clinical feasibility.
Such PRO data, taken together with clinical efficacy and safety data, can assist HCPs in providing holistic care in T2DM that is in line with patient preferences, needs, and values per the principles of evidence-based medicine. The inclusion of PRO data in the product label demonstrates a regulatory acknowledgement of the relevance of the patient perspective as it pertains to the saturated market of antihyperglycemic medication for T2DM, and gives HCPs confidence in the scientific credibility of the PRO endpoint.
Matt Reaney is Senior Scientist, ERT