The challenges
A key hurdle facing the entire pharmaceutical industry is non-adherence by patients to medication. This problem is only likely to be surmounted if patients believe that taking medication will lead to immediate benefits through reduction of symptoms, improvement in physiological functioning and quality of life.
The diabetes mellitus (DM) marketplace, for example, is becoming saturated with multiple medications in both the insulin and pre-insulin space, particularly as analogues start to lose their patents. Differentiation in clinical outcomes within classes is often unclear or minimal. This means that differentiation of therapeutic options is likely to focus more on frequency or mode and method of administration, as opposed to statistically significant differences in glucose control, which are clinically relevant.
What is a measurement strategy?
An effective way of establishing the link between the measured outcome, such as the patient’s health status or quality of life following an intervention programme, is the development of a measurement strategy which requires a clear understanding of the disease and the relevant primary outcomes (e.g. reduced hypoglycemia and secondary outcomes e.g. reduced anxiety).
A patient-reported outcomes (PRO) measurement strategy provides a framework to support the selection of an appropriate PRO for a clinical trial through which treatment effectiveness in terms of health status or quality of life for example, can be demonstrated in relation to the desired primary outcomes.
Components of each of the key stages of the strategy are shown below. This strategy makes explicit the expected treatment effects (e.g. primary biomedical endpoint(s)) AND IMPORTANTLY the secondary endpoints such as reduced anxiety, to be measured by the PRO.
A critical aspect of the measurement strategy is selecting the appropriate PRO that captures the benefits of the primary physiological endpoint of treatment i.e. secondary endpoint(s). However, outcome teams are frequently faced with a plethora of potential PROs each purporting to measure – often without a sound theoretical or measurement model – specific health constructs such as health status or quality of life. As a consequence the choice of a PRO is often made according to:
- the instrument having been used in previous studies
- its name appears to be appropriate for the intended use
- The supporting psychometric data looks o.k.
Furthermore, there is the tendency for those conducting clinical trials to treat the more commonly measured health constructs such as quality of life (QoL), health-related quality of life (HRQoL) and health status as interchangeable in the PRO selection process which they are not. Examples of this include the SF-36 and EQ-5D which are frequently referred to as indicators of QoL, but in fact are more indicators of health status, which of course can impact on the individual’s QoL. Health status is a measure of the quality of health yet while there is no universally accepted definition of QoL, there is the general consensus that it is based on the individual’s subjective evaluation of the psychological and social aspects of their life including work, school and family.
As described above, essential to selecting the appropriate PRO is to make explicit the expected treatment effects e.g. primary biomedical endpoint(s) and the resulting secondary endpoint(s) which should be articulated through the endpoint model from which the most appropriate PRO can be selected. For an example of a simple endpoint model see below.
In this simple model, the objective is to reduce recurrent hypoglycemia which – as the primary endpoint – will be a reduction in the various effects of hypoglycemia including sweating, shaking. etc. Then, as a result, an improvement in the the desired secondary endpoint of the patient’s quality of life will occur. Clearly the model requires further expansion to include which elements of QoL are to be measured as well as health status. Having specified the secondary endpoints the appropriate PRO can then be selected. Central however, to selecting the PRO is the PROs conceptual framework.
What is a PRO conceptual framework?
The PROs conceptual framework shows the item content in relation to the specified concepts/domains the instrument is purported to measure. Therefore, if the PRO has been selected to measure aspects of sleep disturbance as a secondary endpoint, then there must be clear conceptual and psychometric evidence that the items of the PRO should relate directly to these specific construct. Below as an example is the conceptual framework of the Diabetes Health Profile -a PRO developed to assess the psychological and behavioural impact of living with diabetes that was derived on the basis of significant patient input and psychometric evidence.
Not all PROs make explicit their conceptual framework, but it’s worth bearing in mind that evidence 0f a conceptual framework is an essential requirement by the FDA for labeling claims
Summary
Selecting the most appropriate PRO to provide evidence of treatment effectiveness based on the patient’s perspective is a complex process requiring an explicit measurement strategy. This will include defining the primary endpoints and their relationship(s) with the desired secondary endpoints and linking these with conceptual framework of the selected PRO.
Dr Keith Meadows is Founder and Director of DHP Research and Consultancy Ltd. Keith has extensive experience in the field of patient reported outcome measurement with a particular emphasis on the psychological impact of living with diabetes.
