Title: The Prognosis in Palliative care Study II (PiPS2)
Funder: Department of Health and Social Care

Abstract: Background: PiPS-A [1], Palliative Prognostic Index (PPI) [2] and Palliative Performance Scale (PPS) [3] predict survival in patients with advanced cancer and can be calculated without a blood test. PiPS-B [1], Palliative Prognostic (PaP) score [4, 5] and Feliu Prognostic Nomogram (FPN) [6] require a blood test. The relative accuracy of the models, their acceptability to patients, carers and clinicians, and barriers to implementation are unknown. Primary aim: To validate PiPS-A&B and to compare PIPS-B against clinician predictions of survival (CPS). Secondary aims: (1) To validate PaP, FPN, PPI and PPS (2) To determine the acceptability of all prognostic models to patients, carers and clinicians and to identify potential barriers to use. Design: A mixed method approach including a prospective observational validation study and a qualitative interview study. Patients in the validation study will have prognostic scores and CPS recorded. Blood samples will only be collected from patients with capacity who give consent. Patients without capacity will only be included if carers give assent, and no blood specimen will be obtained from these patients. Survival will be tracked by the NHS Information Centre (NHSIC) and will be calculated from date of study entry. Patients, carers and clinicians in the qualitative study will participate in audio-recorded semi-structured interviews which will be transcribed and subjected to Framework Analysis [7]. Setting: A multi-centre UK study involving inpatient hospice units, hospital palliative care teams and community services. Population: The quantitative validation study will include patients with advanced incurable cancer. The qualitative interview study will include a purposive sample of competent patients (+/- carers), carers of non-competent patients, and a sample of clinicians. Inclusion / Exclusion criteria: Patients with or without capacity to consent will be included. Patients will have advanced incurable cancer and have been recently referred to palliative care services. Health technology being assessed: PiPS (www.pips.sgul.ac.uk), PaP, FPN, PPI and PPS. Choice of outcome measures: A range of prognostic models will be studied. We have selected measures that are suitable for use in patients with or without capacity and for those in whom a blood test would or would not be appropriate. Sample size (quantitative study): The total sample size is 1,361. The validation set for PiPS-A is 560, and the sample size to compare PiPS-B with clinician predictions is 1,267. Numbers do not sum to 1,361 because some subjects are in both data sets. Sample size (qualitative study): The final sample size for the qualitative study of patients and carers will be determined by data saturation. It is anticipated that this will be around 30. For the pragmatic evaluation of prognostic instruments among healthcare professionals approximately 15 interviews will be conducted. Timetable: Months 1 – 3; study set-up. Months 3 – 26; recruitment. Months 27 – 36; follow-up, analysis, writing and dissemination. Expertise: We have expertise managing large multi-centre palliative care studies and in the use of mixed methods. Study management, data analysis and statistical expertise will be provided by PRIMENT. Qualitative expertise will be provided by the University of Manchester. Our team includes service users and international collaborators involved in the development of PaP, FPN and PPS

Lay abstract: Background: The term “prognosis” usually relates to the ability of clinicians to predict how long patients will survive. Doctors’ estimates are not very accurate. We developed the Prognosis in Palliative care Scales (PiPS) in order to predict survival in patients with advanced cancer no longer undergoing treatment. In our original study the PiPS was significantly more accurate than either a doctor's or a nurse's best guess about length of survival. Two different PiPS scores can be calculated (PIPS-A and PiPS-B), using routine clinical information (e.g. symptom scores and an assessment of overall health) with or without a blood test (depending upon whether the patient is competent to agree to providing one). Before we can recommend PiPS for routine use it is important to check that the scores remain as accurate and reliable as our original study suggested. PiPS is not the only way to predict survival. Four other scores may also be useful and need to be tested: the Palliative Prognostic Index (PPI) and the Palliative Performance Scale (PPS) can both be calculated without the need for a blood test (like PiPS-A); the Palliative Prognostic (PaP) score and the Feliu Prognostic Nomogram (FPN) both require blood results (like PiPS-B). The primary aims of our study is to check that PiPS is still accurate when we use it in a different group of cancer patients and to compare its accuracy against clinicians’ “best guesses” about how long patients are likely to survive. We will also look at the performance of other prognostic scores; PaP, FPN, PPI and PPS. We will do this by asking patients with advanced incurable cancer, who have recently been referred to palliative (“hospice”) care services, to take part in our study. If patients are able to make a decision for themselves then, with their approval, we will collect information about them from their medical notes and we will take a blood test. If patients are unable to make a decision for themselves (because for instance they are unconscious or delirious), then we will ask their relatives for permission to record information from their medical notes. We will not take blood tests from patients who cannot give permission. With this information we will be able to calculate PiPS, PaP, FPN, PPI & PPS scores. When patients die we will be able to work out the accuracy of the various predictions. We will need to include 1,361 patients over a three year period from 38 different services before we are able to judge whether or not PiPS is valid and better than clinician estimates. In addition to this we will also be asking a selected sample of patients, carers and clinicians about the acceptability of relying on clinicians’ best guesses about survival or the use of one or other of the prognostic tools. We will audio-record and analyse these interviews in order to look for common themes. This information will help us to decide which method of predicting survival is most likely to be used in day-today practice and what is the best way to present this information to patients. Our research team is made up of doctors and scientists who have a lot of experience with undertaking this type of study. Three of the researchers were involved in the original study which developed the PiPS. We will also be working with patient and carer representatives and with researchers from other countries who developed other prognostic scores (PaP, FPN and PPI).

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES;7.2 END OF LIFE CARE
Health categories: CANCER AND NEOPLASMS