UK Stakeholder Perspectives on Surrogate Endpoints in Cancer, and the Potential for UK Real-World Datasets to Validate Their Use in Decision-Making.

Duration of overall survival in patients with cancer has lengthened due to earlier detection and improved treatments. However, these improvements have created challenges in assessing the impact of newer treatments, particularly those used early in the treatment pathway. As overall survival remains most decision-makers' preferred primary endpoint, therapeutic innovations may take a long time to be introduced into clinical practice. Moreover, it is difficult to extrapolate findings to heterogeneous populations and address the concerns of patients wishing to evaluate everyday quality and extension of life. There is growing interest in the use of surrogate or interim endpoints to demonstrate robust treatment effects sooner than is possible with measurement of overall survival. It is hoped that they could speed up patients' access to new drugs, combinations, and sequences, and inform treatment decision-making. However, while surrogate endpoints have been used by regulators for drug approvals, this has occurred on a case-by-case basis. Evidence standards are yet to be clearly defined for acceptability in health technology appraisals or to shape clinical practice. This article considers the relevance of the use of surrogate endpoints in cancer in the UK context, and explores whether collection and analysis of real-world UK data and evidence might contribute to validation.

A qualitative investigation of patients' and caregivers' experiences of severe sepsis*.

OBJECTIVES: To explore and describe the subjective experiences and long-term impact of severe sepsis on survivors of severe sepsis and their informal caregivers (e.g., spouse or family member) through qualitative research methods. DESIGN: A qualitative exploratory study using semi-structured interviews with survivors of severe sepsis and their informal caregivers in the United Kingdom and United States. Participants also completed a demographic background form and sites provided medical history details. Transcripts were analyzed using a thematic analysis approach. SETTING: Patients were recruited from a large National Health Service hospital in the United Kingdom and a level 1 trauma center hospital in the United States. Caregivers were recruited through eligible patients. Interviews were conducted either face to face in participant's homes or another convenient location or over the telephone. PATIENTS: Patients who were 18 years old or older and had experienced an episode of severe sepsis in the previous 12 months were recruited by clinical staff in each hospital. Caregivers were family members or friends who had provided informal care for the patient after their episode of severe sepsis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Thirty-nine interviews were conducted with 22 patients and 17 informal caregivers (of these 28 were conducted face-to-face and 11 by telephone). Five main themes were identified in the qualitative analysis: awareness and knowledge of severe sepsis; experience of hospitalization, ongoing impact of severe sepsis; impact on caregivers; and support after severe sepsis. Experiences varied depending on the patients' health prior to the severe sepsis, with the worst affected reporting lasting impacts on multiple aspects of their life. CONCLUSIONS: The study extends what was understood about severe sepsis from the patients' and caregivers' perspectives from the previous limited literature. Caregivers as well as patients reported enduring impact. The study also identified problems of lack of awareness of diagnosis and understanding of severe sepsis by patients and caregivers and difficulties accessing appropriate healthcare providers and ancillary services after discharge from hospital.

The impact of describing clinical trial treatments as new or standard.

Concern has been expressed over a possible widespread belief amongst patients in trials, that a new treatment is better than the standard, despite the lack of evidence of such superiority. A sample of the general public (N = 130) read a leaflet describing a hypothetical trial comparing two similar treatments for either arthritis or back-pain. Half read that both treatments were standard and generally available; half that one was new and available only within the trial. Participants rated any preference for one or the other treatment, gave written reasons, and indicated their willingness to enter the randomized trial. Fifteen participants subsequently talked through their answers. Most participants expressed no preference for either treatment when both were described as standard. When one was new more people with the arthritis (but not the back-pain) scenario expressed a preference (chi2 = 5.44, P = 0.031). Importantly, this was not more likely to be for the new treatment. Rationally, those who preferred a freely available treatment were less likely to participate in the trial (chi2 = 23.3, P < 0.001). The mere description of a trial treatment as new was insufficient to engender a preference for it over a standard treatment, although it may contribute to preference under certain additional circumstances.