Traditionally, the success or otherwise of medical treatments has been assessed by mortality or clinical assessments of health. However, patient self-reports of health are increasingly seen as central to the evaluation of health and healthcare interventions.

In the Valid Insight webinar ‘Patient-reported outcomes in clinical trials and studies,’ we discussed the clinical implications of PROs and how central these have become to medical care assessment.¹

Clinical applications of PROs

A PRO is an instrument that evaluates an intervention from the patient’s perspective, without a clinician’s interpretation. PROs can be used to assess overall health status, perceptions of one’s own health, impact of disease on daily activities, severity of symptoms, and at times experience of treatment.

PRO instruments can provide information to facilitate stakeholder decision-making. Potentially, they can be used to target resources to the needs of the population served, deliver individualised patient care, provide clinical assessment/screening, evaluate costs and quality of life (QoL) benefits of care, and provide end points in randomised clinical trials (RCT). For example, in a clinical trial conducted for Parkinson’s disease (PD), the effect of using Levodopa-sparing treatments on QoL was tested. Levodopa is a chemical used to treat PD. Over time, the impact of levodopa on PD tends to wear off. Levodopa-sparing treatments are intended to extend its effect. In a large scale randomised controlled trial, it was found that using Levodopa-sparing treatments did not improve self-reported mobility and overall QoL, as measured on a disease-specific PRO, the Parkinson’s Disease Questionnaire. Clearly, the idea of using sparing drugs initially seems clinically favourable, but the trial results suggest that such treatments have no real benefit in terms of patient self-reported health.

Selecting or developing PROs

Companies can choose to either select a generic scale or develop a disease-specific scale. The Short Form 36 (SF-36) is an example of a generic scale that can be used to compute mental health and physical health summary scores. Patient results from this scale can also be compared with general population results.

As with the PD study, a new questionnaire can also be developed. Indeed, the Food and Drug Administration (FDA) suggests that companies develop PROs specifically tailored to the disease of interest. However, PRO development can be lengthy and can readily cost between US$100,000 and US$1.2 million, depending on the complexity.

The characteristics of a well-developed PRO

Both the FDA and the European Medicines Agency (EMA) are showing interest in including PROs in their assessments. The FDA is strict on defining the therapeutic benefit and having very clear endpoints. The instrument used must be appropriate, well developed, adequately validated, and reliable.

Validity takes three forms:

• Content validity – the degree to which the questions represent the important elements to the disease/treatment.
• Construct validity – the degree to which the instrument really measures what it claims to measure.
• Criterion validity – the extent to which the instrument relates to or predicts an outcome.

The PRO instrument must also be reliable by having internal consistency, where there is a correlation between the questions within each domain, and test-retest reliability, where it yields similar, stable numbers over time.

Selecting or designing PROs is not just a case of picking one off the shelf. Companies need to clearly indicate that their questionnaire has appropriate measurement properties, measures exactly what it says it will measure, and is appropriate for the study endpoint.

PROs and payer assessment

PROs can help demonstrate the value of a drug, including its economic value. Health economic evaluation can be achieved through three measures: cost benefit, cost-effectiveness, and cost utility. Cost utility, in particular, is analysed by measuring the Quality Adjusted Life Years (QALY), which is a single index measure for health benefits that divides cost by the number of years gained from a treatment, adjusted by QoL. For example, a drug that costs US$1,000, offers a 10-year gain, and has a 0.80 QoL ratio will have a QALY of US$125. QALYs reflect both morbidity and mortality, which are intervention facets that payers greatly consider.

At times, PRO results may be the best way for patients to differentiate between products. For instance, in scenarios where competing treatments cannot prolong life [or are therapeutic equivalents], the drug developer’s next objective should be to offer better life, which is something that a patient alone can assess. Additionally, offering a QoL benefit can tremendously influence patient compliance and prescriber decision-making. Therefore, using PROs enables a company to be the first to go to market with specific QoL labelling claims. This is a huge differentiator. Overall, PROs can echo the patient voice and aid pharma in shifting towards a patient-centric value proposition.

The role of PROs in payer assessment is clearly growing. In the future, they are likely to become standard instruments in pricing and reimbursement decisions. Soon, PRO instruments will help ensure the right patients can access medicines offering the physiological and QoL benefits they value.

To learn more about selecting or designing PRO measures for your clinical trial or study, call us on: +44(0) 203 750 9833 or email us at: discover@validinsight.com

1. Valid Insight (2016). Webinar: Patient-reported outcomes in clinical trials and studies. Retrieved from https://validinsight.com/events-news/patientreported-outcomes-webinar/