Title: RecUrrent Intra-articular Corticosteroid injections in Osteoarthritis; the RUbICOn study
Funder: Department of Health and Social Care

Abstract: Osteoarthritis is a condition that causes joints to become painful and stiff, it is a common cause of pain and disability. Management of osteoarthritis involves reducing pain and maintaining function. Simple treatments include activity modification, staying active to maintain muscle strength and taking pain medication. Complex treatments include joint replacement (replacing the painful joint with an artificial joint), which may be required for those with pain that cannot be well controlled by other means. Before a joint replacement is considered, it is possible to use other techniques, such as injections into the affected joint, to try to reduce pain. These injections are most commonly used for knee osteoarthritis. The injection usually contains both an anaesthetic to help with the pain and a steroid to reduce the inflammation (swelling, redness, heat and pain) within the joint. It is known that these injections can help with pain if used infrequently and that their use is recommended by a variety of organisations, including the NHS. However, little is known about the effect of using repeated injections. _x000D_ _x000D_ We wish to use data that has already been collected on patients treated for osteoarthritis in primary care (by their GP or a physiotherapist) who have or have not received an injection. Using this data, we will look at current use of injections, the safety of their use, how good they are, and whether they affect other treatments and the timing of these. We will also interview people involved in this treatment (patients and healthcare professionals) to help understand their experience of the treatment, attitudes to its use, how best it can be used, the acceptability of future research in this area and what are the most important outcomes that should be assessed. We will also invite patients, healthcare professionals and commissioners to take part in questionnaire surveys to find out what the important questions are that need to be answered by any studies in the future, whether it would be possible to do these studies and how they should be conducted. _x000D_ _x000D_ The information we generate will be important in helping us understand how these injections are currently used and how practice and care for patients could be improved. It will also help to find out what future research in this area is needed and the most acceptable way of doing this._x000D_ _x000D_ We have discussed the study with our patient and public involvement group, the Patient Experience Partnership in Research (PEP-R) group, an established forum of 8 service users with musculoskeletal conditions. They agreed that it was important to look at the results of treatment with injections for osteoarthritis. Members of the group had experience of receiving injections for osteoarthritis and sites included the knee and hand. Some group members had experienced problems with receiving injections as not all the GPs in their practice performed them and some only injected certain joints. They felt that it was important to establish whether injections helped with pain and how safe they were to use, including whether there should be a limit to the number received and over what period of time. They also felt it was very important to look at whether injections led to a delay in other procedures such as joint replacement. The PEP-R group members provide very useful feedback and input for the plain English summary and have offered to provide ongoing support throughout the study.

Lay abstract: AIMS:_x000D_ Establish current practice of use of intra-articular corticosteroid injection (IACI) for the treatment of joint pain due to osteoarthritis (OA)._x000D_ Establish the long-term safety and outcomes of the use of recurrent IACI._x000D_ Explore views and experiences of patients and clinicians of the use of IACI._x000D_ Assess the feasibility of future primary research._x000D_ _x000D_ SETTINGS: 3 large prospective routinely collected datasets: Clinical Practice Research Datalink (CPRD) with linkage to Hospital Episode Statistics (HES) and National Patient Reported Outcomes Measures (PROMs) data. Qualitative interviews with patients and primary healthcare professionals and a Delphi survey of these groups, researchers and commissioners._x000D_ _x000D_ POPULATION: CPRD: Feasibility estimates indicate approximately 25000 patients with knee, 9000 with hip, 5000 with hand, 3000 with shoulder, 2000 with ankle/foot and 1000 with wrist/elbow OA have received IACI with >100000 control cases available. For the knee (most common IACI site), using a 2-sided log rank test for equality of survival curves, 90% power and 5% significance level, where outcome is time to arthroplasty and an anticipated arthroplasty rate of 7% over 4-years we can detect a hazard ratio of 0.85 (equivalent to a 7% arthroplasty rate in non-IACI users and 6% in IACI users) with a total sample size of 24,613 (12,300 in each group). Qualitative interviews: 40 patients and 30 General Practitioners (GPs). Delphi survey: 25 patients, 25 healthcare professionals, 25 researchers, 25 commissioners._x000D_ _x000D_ METHODS:_x000D_ WP 1: Data linkage of CPRD-HES-PROMs datasets. Current practice will be described by analysis of population, practice and patient level data including secular trends. Safety (pain, bleeding, infection, diabetes, cardiovascular) and association of IACI with outcomes (drug utilisation, timing to surgical intervention, subsequent outcome of arthroplasty, PROMs). Instrumental variables will be used as the primary analysis if key assumptions are met. The instrument will be based upon clinician preference for IACI. Sensitivity analyses will be performed with propensity score matching, inverse probability weights to explore the potential for unmeasured confounding_x000D_ WP 2: Semi-structured in depth interviews will be performed. Healthcare behaviour theories will be used to inform the analysis._x000D_ WP3: 3-round modified Delphi study of patients, healthcare professionals, researchers & commissioners to identify future primary research priorities and associated feasibility._x000D_ _x000D_ TIMELINES (month):_x000D_ 1: CPRD-HES-PROMs data extraction, linkage and management; commence qualitative interview documentation development_x000D_ 4: commence utilisation and safety analysis_x000D_ 5: commence patient and clinician recruitment and qualitative interviews_x000D_ 9: interim statistical results meeting, commence outcomes analysis_x000D_ 15: interim statistical results meeting_x000D_ 16: commence Delphi survey_x000D_ 21: complete statistical analysis_x000D_ 24: complete qualitative data collection and analysis; complete round 1 of Delphi survey _x000D_ 24-30: complete qualitative study and Delphi survey, write up, dissemination_x000D_ _x000D_ ANTICIPATED IMPACT & DISSEMINATION: inform evidence base to guide use of repeated IACI. Establish feasibility of primary research. Dissemination: written HTA report; peer-reviewed publications in journals (e.g. BMJ); NHS patient resources, Health Integration Teams; through RCGP, RSM, academic research networks and NIHR funded research centres

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: MUSCULOSKELETAL