FP-00034

Section 1 - Basic information about you and your application:

Title of research project
Developing a core outcome set for studies of patients sustaining periprosthetic femoral fractures.

Grant Type
The ORUK Inspiration Fund

Research area
Diagnostic and treatment

Duration
8 months

Start date
December 1, 2023

Have you previously received funding from ORUK?
No.

Profession
Orthopaedic surgeon

Your current job title/position
ST1 NIHR Academic Clinical Fellow (out of programme due to health)

Are you an early-career researcher (ECR)? (definition of ECR)
no

Section 2 - Lay summary

Lay summary:

Hip and knee replacements are used to treat worn out and damaged joints. In 2021, 162,828 patients received either a hip or knee replacement in the United Kingdom. The operations are generally very successful, but problems can happen. One of these problems is when the bone that supports the hip or knee replacement breaks. This needs emergency surgery and can permanently leave the patient with pain and poor movement. When this occurs in the thigh bone (femur), this is called a periprosthetic femoral fracture (PPFF). These injuries are the most common reason for a hip replacement to fail. The exact number of PPFFs that occur in the United Kingdom (UK) and worldwide are poorly understood due to the different ways they can be treated, but best estimates suggest that at least 3,500 cases occur in England and Wales alone each year. As the population live longer, more active lives, this number is expected to increase.

We want to learn more about how to improve care for patients who suffer this injury, but before we can do this, we need to know which aspects of their recovery patients think are most important. At the moment, each researcher comes up with their own priority, which is flawed as they may not be what patients want and we can’t compare the results of different studies. Core outcome sets (COS) tell researchers which outcomes are most important to patients and healthcare professionals, so that everyone is on the same page and considers the same important outcomes. Right now, there is no core outcome set for PPFF.

This study aims to undertake the first steps in producing a core outcome set using a process that we already know works well. We will first look at other studies and summarise what outcomes are already used. For the second step, we will review interviews that were previously conducted by another researcher, who spoke to patients with PPFF about their experience and recovery. These interviews will allow us to identify any other outcomes that patients think are important.

Using this information, our future studies will then work with patients, carers and healthcare professionals to identify the ones most people think are the most important. Once these have been identified, we will host meetings to finalise which items should be included in the final core outcome set.

Section 3 - Purpose of research

Purpose of research:

Study Aim

• To conduct preliminary work to inform the future development of a core outcome set for studies of patients who sustain a periprosthetic femoral fracture.

Study Objectives

1. Register the study on the COMET database (to be completed immediately following confirmation of funding).
2. To perform a systematic review of outcomes currently reported in studies of PPFF.
3. To identify additional outcomes relevant to patients who have suffered PPFF via secondary analysis of previously conducted qualitative interviews
4. Summarise the outcomes identified via the systematic review and secondary analysis of interviews into a long list of outcomes for use in a future modified Delphi process.

Future objectives

We anticipate that objectives 1-4 will fill the eight-month study period proposed. Further funding will then be sought to complete the following steps. If objectives 1-4 are met within the timeframe however, we will continue to work through steps 5-7 as time and funding allow.

5. To reduce the long-list of outcomes by grouping similar items together into domains to create a Delphi questionnaire ready for use.
6. Prioritisation of outcomes using a modified Delphi technique.
7. To conduct consensus meetings with patients and professionals to agree on the final COS.

Section 4 - Background to investigation

Background to investigation:

Background

A periprosthetic fracture is one associated with an implant. In the femur this can occur around a joint replacement or fracture fixation device.(1) Their management is challenging; being influenced by fracture location, implant stability, host bone stock and functional status.(2) Surgery for a periprosthetic femoral fracture (PPFF) is technically complex, expensive and places significant physiological demand on a predominantly frail cohort of patients.(3-5) For individuals, the impact of PPFF can be devastating, with associated loss of independence and inpatient mortality of 4.3-11%.(4-6)

Around the world, patients are living longer, more active lives.(7) Coupled with advances in joint replacement, this has created a dramatic increase in the number of individuals living with, and demanding more of, orthopaedic implants.(6) As a result, the estimated incidence of PPFF has been reported as rising by as much as 13% each year between 2015 and 2018.(6) Despite this increasing incidence, research around PPFF remains in its infancy due to availability of reliable, accurate and generalisable data. PPFF have therefore been highlighted as areas of importance by both the British Hip Society (BHS) and the British Association for Surgery of the Knee (BASK).

A core outcome set (COS) is an agreed standardised set of outcomes that should be measured and reported, as a minimum, in observational studies where possible and all clinical trials in specific areas of health or health care.(8) They reduce heterogeneity between studies, facilitate evidence synthesis, and reduce the risk of reporting bias. Their development utilises input from key stakeholders (including patients) and therefore helps to identify the most clinically relevant outcomes. To date a COS for PPFF has not been developed and therefore outcome reporting is not standardised. Although a COS has been developed for native hip fractures, differences in the  demographic, treatment and recovery of the two populations exist.(9,10) At the time of submission, no other research group have registered the development of a PPFF COS on either the Core Outcome Measures in Effectiveness Trials (COMET) or International Prospective Register of Systematic Reviews (PROSPERO) databases.

Personal track record

Throughout my training, I have actively engaged in various areas of research from bench to bedside. These include a Master of Science by Research in the epigenetics of colorectal cancer, a position on the competitive Severn Academic Foundation Programme and an Operations Committee position within the international COVIDSurg Collaborative. Each have expanded my understanding of research methodologies and evidence-based medicine. I previously published a systematic review and meta-analysis on the impact of delayed fixation of hip fractures on mortality.(11) That project, together with my clinical work, has fuelled an interest in how we can improve outcomes for older patients with musculoskeletal injuries. Recently I have worked with surgeons and orthogeriatricians at the National Hip Fracture Database to produce two manuscripts on the topic of PPFF (one published in Bone and Joint Open, one under review).(12) Given the growing clinical burden and research interest associated with PPFF, I believe that this is an exciting and clinically important area to be involved in.

Preliminary data

A previous PhD candidate, conducted 20 in-depth semi-structures interviews of patients who had suffered PPFF.(13) Interviews explored the psychological and physical impact of PPFF. Objective three of the proposed study will review interview transcripts in order to identify additional outcomes not captured by the systematic review.

References

1. Capone A, Congia S, Civinini R, Marongiu G. Periprosthetic fractures: epidemiology and current treatment. Clin Cases Miner Bone Metab. 2017;14(2):189-96.
2. Ohly NE, Whitehouse MR, Duncan CP. Periprosthetic Femoral Fractures in Total Hip Arthroplasty. HIP International. 2014;24(6):556-67.
3. Phillips JR, Boulton C, Morac CG, Manktelov AR. What is the financial cost of treating periprosthetic hip fractures? Injury. 2011;42(2):146-9.
4. Johnson-Lynn S, Ngu A, Holland J, Carluke I, Fearon P. The effect of delay to surgery on morbidity, mortality and length of stay following periprosthetic fracture around the hip. Injury. 2016;47(3):725-7.
5. Moreta J, Uriarte I, Ormaza A, Mosquera J, Iza K, Aguirre U, et al. Outcomes of Vancouver B2 and B3 periprosthetic femoral fractures after total hip arthroplasty in elderly patients. HIP International. 2019;29(2):184-90.
6. Bottle A, Griffiths R, White S, Wynn-Jones H, Aylin P, Moppett I, et al. Periprosthetic fractures: the next fragility fracture epidemic? A national observational study. BMJ Open. 2020;10(12):e042371.
7. Department of Economic and Social Affairs. World Social Report 2023: Leaving no one behind in an aging world. United Nations. 2023. https://www.un.org/development/desa/pd/sites/www.un.org.development.desa.pd/files/undesa_pd_2023_wsr-fullreport.pdf (Accessed 04/06/2023).
8. COMET Initiative. Core Outcome Measures in Effectiveness Trials. https://www.comet-initiative.org(Accessed 18/04/2023)
9. Haywood KL, Griffin XL, Achten J, Costa ML. Developing a core outcome set for hip fracture trials. Bone Joint J. 2014; 96-B(8):1016-23.
10. No authors listed . Improving Understanding – The National Hip Fracture DatabaseReport on 2021 (NHFD 2022 annual report). Royal College of Physicians . 2022 . https://www.nhfd.co.uk/2022report (accessed 13/07/2023)
11. Welford P, Jones CS, Davies G, Kunutsor SK, Costa ML, Sayers A, Whitehouse MR. The association between surgical fixation of hip fractures within 24 hours and mortality: a systematic review and meta-analysis. Bone Joint J. 2021;103-B(7):1176-1186.
12. Jones CS, Eardley WGP, Johansen A, Inman DS, Evans JT. Caring for patients with periprosthetic femoral fractures across England and Wales in 2021. Bone Jt Open. 2023 23;4(5):378-384.
13. Carpenter FVE. The impact of adverse events following total hip replacement [Doctoral thesis]. University of Bristol; 2021. http://bit.ly/43zJqek (accessed 13/07/2023)

Section 5 - Plan of investigation

Plan of investigation:

Phase 1: Systematic review of the literature to identify reported outcomes

Data sources:

The conduction and reporting of this systematic review will be performed in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.(1) The Cochrane Register, Ovid EMBASE, Web of Science and Ovid MEDLINE databases will be searched using search terms developed in conjunction with a medical librarian. The following trial registries will also be screened for ongoing studies: ISRCTN, ICTRP, and ClinicalTrials.gov. References of included articles and systematic reviews will be screened.

Inclusion criteria:

Original research articles reporting outcomes of patients following PPFF will be included. This will include patients who sustain fractures around or between hip or knee implants. An implant will be defined as any orthopaedic device including arthroplasty or fracture fixation device e.g. sliding hip screw, plate or nail. The search will be limited to a ten-year period from January 2014 to December 2023 to reflect use in contemporary PPFF studies. Systematic reviews will be included to identify novel outcomes (e.g. new composite outcomes).(2) Study protocols will be reviewed where referenced.

Exclusion criteria:

Case reports and conference abstracts will be excluded. Studies reporting periprosthetic fractures affecting bones other than the femur, e.g. humerus, are beyond the scope of the current review. Other exclusion criteria include studies of cadaveric and non-human animals, and non-English articles.

Study identification and data extraction:

Titles will be screened by one reviewer and clearly irrelevant texts will be excluded. Titles, abstracts, and full texts of potentially relevant texts will then be screened independently by two reviewers using the Rayyan platform.(3) Disputes will be settled by discussion with the project supervisors.

Data extraction will be completed using a standardised proforma (Google Sheets, USA). Extracted data will include: Study details (title, authors, year, journal, study design), study setting (country, number of centres), patient population (number, age, sex, fracture site, implant), interventions received (e.g. revision, fixation, non-operative), reported outcomes, outcome definitions, outcome measurement, and outcome time points. Reported outcomes will be recorded verbatim. Where a citation is used to define an outcome, the definition will be copied from the cited article. Data extraction will be completed by a single researcher and 20% will be checked by a second reviewer.

Assessment of bias:

We aim to identify all outcomes reported irrespective of the study quality and therefore no formal quality assessment will be undertaken.

 

Phase 2: Secondary analysis of interviews

To identify additional outcomes that are important to patients, but overlooked in the published literature, secondary analysis of previously conducted semi-structured interviews will be performed.(4) In brief, 20 patients who had previously sustained PPFF around a total hip replacement were interviewed to explore the physical and psychological experience of their injury.(4) These interviews were audio-recorded, transcribed and anonymised. Secondary analysis of transcripts provides a time-efficient and cost-efficient approach to identifying outcomes that are important to patients.

Secondary thematic analyses of these transcripts will be conducted, identifying relevant outcomes for inclusion in the long list. To ensure a rigorous approach to analysis, at least five (25%) transcripts will be independently coded by two members of the research team.

 

Phase 3: Organisation of a long list of candidate outcomes

Development of the long list of candidate outcomes will follow published methodology on the development of unique outcomes.(5,6) A list of verbatim outcomes identified in phases one and two will be developed. Identical verbatim outcomes will be identified as duplicates and deleted. Outcomes that have the same meaning but are written differently will be re-written independently by two members of the research team to develop a non-verbatim outcome list. This will be performed in collaboration with a patient and public involvement group (PEP-R), based in the Musculoskeletal Research Unit. These non-verbatim outcomes will be organised and categorised using the COMET Taxonomy of Outcomes.(7)

 

Dissemination

A summary of outcomes identified will be presented in full and submitted for peer review publication. To maximise reach, we aim to supplement this with other methods of dissemination including conference presentations, infographics, and plain language summaries.

 

Future work:

The work described is anticipated to fill the proposed study period. We will then apply for further funding to complete development of the PPFF COS (note if phases 1-3 are completed within the study period, we will proceed as funding and time permit).

In brief, the long list of outcomes will inform the development of a Delphi questionnaire. After REC and HRA approvals are obtained, patients with experience of PPFF and professionals from the multi-disciplinary team will be invited to participate in a modified Delphi process. Participants will be asked to rate the importance of each outcome from 1-9 (not important to very important) with interpretation and analysis as per The RAND/UCLA Appropriateness Method.(8) Three rounds of the survey will be conducted, with feedback provided after round two and with only the outcomes considered most important (according to pre-defined criteria) progressing beyond round two. A consensus meeting will be held, including patients and healthcare professionals, to determine the items for inclusion in the final COS.

 

 References:

1. Preferred Reporting Items for Systematic Reviews and Meta-Analyses. PRISMA checklist. 2009. http://www.prisma-statement.org/PRISMAStatement/Checklist.aspx (Accessed 14/07/2023)
2. Aquilina AL et al. What outcomes have been reported on patients following open lower limb fracture, and how have they been measured? Bone Joint Res. 2023;12(2):138-146.
3. Ouzzani M et al. Rayyan—a web and mobile app for systematic reviews. Syst Rev. 2016; 5: 210.
4. Carpenter FVE. The impact of adverse events following total hip replacement [Doctoral thesis]. University of Bristol; 2021. http://bit.ly/43zJqek (accessed 13/07/2023)
5. Young A, et al. A systematic review of core outcome set development studies demonstrates difficulties in defining unique outcomes. J Clin Epidemiol 2019;115:14-24.
6. Williamson P, et al. The COMET Handbook: version 1.0. Trials 2017;18(Suppl 3):280.
7. Dodd S et al. A taxonomy has been developed for outcomes in medical research to help improve knowledge discovery. J Clin Epidemiol. 2018;96:84–92.
8. Fitch K, et al. The RAND/UCLA Appropriateness Method User’s Manual. Santa Monica: RAND; 2001.

Section 6 - Research environment and resources

Research environment and resources:

Research support (Individuals and centres anonymised as per guidance notes) 

This work will be conducted between two centres have a pre-existing strong working relationship.

Supervisor 1 is an academic hip surgeon and professor of orthopaedic surgery. He has extensive experience in evidence synthesis, qualitative data analysis, clinical trials and Delphi techniques. He will provide overall supervision and expertise in PPFF.

Supervisor 2 works between the two centres. His main research interest is the management of PPFF and he contributes to multiple research groups exploring the topic. He will provide day to day supervision of the project.

Collaborator 1 is a consultant knee surgeon and research lead at one of the centres. He sits on multiple national committees and will provide expertise in PPFF around the knee.

Collaborator 2 is an Associate Professor. She has expertise in qualitative techniques, the Delphi methodology and development of COS. She will provide methodological support in the secondary analysis of interviews and future modified Delphi work.

Laboratory space

Not required.

 

Equipment 

Given the nature of this study, no specialist equipment will be required. Articles for the systematic review will be acquired through University access and inter-library loans. The interview transcripts will be anonymised prior to our acquisition.

Additional funding

No additional funding at present.

Section 7: Research impact

Who will benefit from this research?

Personal

I am currently interrupting my NIHR Academic Clinical Fellowship in orthopaedic surgery (ST1) due to health reasons. I am passionate about orthopaedic research and this funding would allow me to continue contributing to the field whilst out of training. This work will form the foundation of a PhD application to continue exploring and improving the care of patients with PPFF, including completion of the COS.

Institutional

Our centres are currently involved in numerous multi-centre projects within the field of PPFF. We have identified the need for a COS and leading its development would secure our positions as leading centres within the field.

Patients

Our understanding of the prevention and optimum management of PPFF remains poorly understood. Maximalising the interpretability of research in this area, has the potential to translate directly into improvements in patient care.

How can your research be translated in real-life?

Despite clinical concerns around the rising incidence of PPFF, research in the field remains in its relative infancy. To date there is no COS for this condition and as a result, there is considerable heterogeneity in the outcomes reported between studies. This hinders evidence synthesis and allows potential research waste. A COS provides the minimum agreed standardised set of outcomes that should be measured and reported in clinical trials. As the number of studies exploring this important clinical topic increase, the generation of a COS, has the potential to minimise heterogeneity and maximise interpretability of PPFF research. This will directly translate into improved trial design and reporting.

How will your research be beneficial for ORUK and its purpose?

ORUK has established itself as a leading body in the support of musculoskeletal research in the United Kingdom. We hope that we have highlighted the burden that PPFF pose to the orthopaedic community, the need for a COS within this area and the likely interest in our outputs. We believe that the proposal described here is pragmatic and achievable, allowing us to maximise the odds of completion and quantifiable outputs such as publication and presentation. ORUK will be acknowledged for its contribution to the identification of PPFF outcomes, and the future development of a PPFF COS. In supporting this invaluable work, ORUK will be helping to improve the quality of PPFF research which will directly better our care for patients with these devastating injuries.

Section 8: Outreach and engagement

We are keen to ensure that the non-academic public benefit from this work. We aim to produce plain language summaries and infographics for public dissemination on social media. We will engage with our two university press offices to discuss promotion of the study findings on their respective websites. The findings will also be used to produce promotional material (posters and a video) to encourage stakeholder involvement in the subsequent modified Delphi process.

Section 9: Research budget

Requested funding from ORUK

University fees (if any)
£8914.44

Salary
£27163.33

Consumables
£720

Publications
£3000

Conference attendance
£1000

Other items
£0

Total 'requested fund'
£40797.77



Other items
No additional items. To clarify: - University fees consist of National Insurance, pension and apprenticeship levy as per University finance department. - Consumables: Cost of patient and public involvement group (£720 for 9 members at £25 per hour for 3 hours (1 hour prep, 2 hours meeting + £5 WaH costs for each member)



Other secured funds

Internal funding
£0

Partner (University)
£0

Partner (Commercial)
£0

Partner (Charity)
£0

Other sources
£0

Total 'other funds)
£0

Section 10: Intellectual property and testing on animal

Is there an IP linked to this research?
No

Who owns and maintains this patent?


Does your research include procedures to be carried out on animals in the UK under the Animals (Scientific Procedures) Act?
No

If yes, have the following necessary approvals been given by:

The Home office(in relation to personal, project and establishment licences)?


Animal Welfare and Ethical Review Body?


Does your research involve the use of animals or animal tissue outside the UK?
No

Does the proposed research involve a protected species? (If yes, state which)



Does the proposed research involve genetically modified animals?


Include details of sample size calculations and statistical advice sought. Please use the ARRIVE guidelines when designing and describing your experiments.


There should be sufficient information to allow for a robust review of any applications involving animals. Further guidance is available from the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), including an online experimental design assistant to guide researchers through the design of animal experiments.

Please provide details of any moderate or severe procedures


Why is animal use necessary, are there any other possible approaches?


Why is the species/model to be used the most appropriate?