Exploring efficacy, cost effectiveness and experiences related to adherence of different bisphosphonate regimens for the prevention of osteoporotic fragility fractures (The BLAST OFF Study)
| ISRCTN | ISRCTN10491361 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN10491361 |
| IRAS number | 271732 |
| ClinicalTrials.gov number | NCT04283786 |
| Secondary identifying numbers | 43961, IRAS 271732 |
- Submission date
- 09/12/2019
- Registration date
- 04/02/2020
- Last edited
- 22/04/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Musculoskeletal Diseases
Plain English summary of protocol
Background and study aims
Osteoporosis is a condition where bones become weak and fragile and can easily break. Suffering from one fragility fracture doubles your chance of having another. These fractures can affect a person’s life significantly and contribute to significant costs to the UK health service.
Bisphosphonates are used to treat osteoporosis and help prevent fractures. The most commonly used bisphosphonate treatment is Alendronate, but taking it correctly is complicated and side-effects are common. Therefore only 1 in 4 people continue with Alendronate beyond 2 years. There are different forms of bisphosphonates that can be given in different ways and frequencies and may be more acceptable and tolerated by patients.
The study will look at how effective different bisphosphonate regimens are compared to Alendronate at preventing fractures, whether the reduction in fracture risk can be achieved at reasonable financial cost and establish acceptability of different approaches to patients.
Who can participate?
All adults over the age of 18 with the ability to give informed consent who fulfil the criteria for one of these stakeholder groups:
- GPs
- Patients who started on oral bisphosphonates within the last 24 months for prevention of fragility fractures
- Secondary care specialist clinicians (nurses, consultants) involved in the treatment of osteoporosis
- Patients receiving hospital based (intravenous) bisphosphonate treatments for prevention of fragility fractures who began treatment within the last 24 months
- Clinical academics involved in osteoporosis research
- Specialist clinicians (nurses, consultants) from the osteoporosis service in Nottingham and Sheffield with insight into alternate bisphosphonate treatments
- Patients receiving alternate bisphosphonate treatments for prevention of fragility fractures who began treatment within the last 24 months
- Commissioners involved in osteoporosis services
What does the study involve?
The study will be completed in 3 stages.
Stage 1A will update a previous review of published literature (systematic review) to inform which bisphosphonate regimens are most effective at reducing fractures and use a health economic model to analyse which regimen provides the best value for money. Additional studies will be included and data to look at treatment compliance and long-term persistence (adherence) and treatment safety and side-effects. This stage will not involve any study participants.
Stage 1B will consist of qualitative semi-structured interviews from a sample of stakeholders in receipt of or involved in the delivery of different bisphosphonate regimens, in order to identify which regimens are most acceptable to patients. A scoping review will help develop an iterative interview topic guide in order to explore the views, experiences and preferences of different bisphosphonate regimens from patients, clinicians and researchers, and analysed to inform the issues of treatment adherence. This methodology has been chosen in order to collate pragmatic information on this area and explore uncertainties to help inform future research questions that should be addressed in order to improve care in this area.
Stage 2 will engage stakeholders (patients, clinicians, researchers, commissioners) in focus groups and workshops to discuss uncertainties from Stage 1 and identify the most important outstanding questions for future research. These stakeholder meetings will be arranged with support by the Royal Osteoporosis Society and prioritised research questions formed using the James Lind methodology. Stakeholders will not be invited via NHS organisations, and no identifiable information will be collected. Use of the Health Research Authority decision tool identifies that this stage does not require NHS ethical approval.
What are the possible benefits and risks of participating?
There are no specific benefits or risks to participants as there is no treatment interventions associated with the study.
There is a burden to participants in terms of time and inconvenience of taking part in an interview. This will be minimised using an iterative approach to interview guides to maximise efficiency of the semi-structured interview topics, minimise travel by offering several options for the interview setting to participants, and offer an inconvenience allowance.
Rarely there may be a participant disclosure during interview that is a safeguarding concern. The researcher will inform the participant that they have a duty to report their concern of harm to the participant or others to a relevant healthcare professional, initially the Chief Investigator of the study, for referral on as deemed necessary.
Where is the study run from?
Nottingham University Hospitals NHS Trust, Nottingham, UK
When is the study starting and how long is it expected to run for?
September 2019 – April 2022 (updated 10/03/2021, previously: October 2021)
Who is funding the study?
National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Programme; project reference NIHR 127550
Who is the main contact?
Professor Opinder Sahota (Chief Investigator)
Opinder.sahota@nuh.nhs.uk
Rachael Taylor (Study Coordinator)
Rachael.taylor@nuh.nhs.uk
Contact information
Scientific
Nottingham University Hospitals NHS Trust
B Floor, South Block
Queens Medical Centre
Nottingham
NG7 2UH
Telephone: 01159249924
Email: Opinder.sahota@nuh.nhs.uk
Nottingham
NG7 2UH
United Kingdom
 ORCID ID |
0000-0003-0055-7637 |
|---|---|
| Phone | +44 (0)115 9249924 |
| Opinder.Sahota@nuh.nhs.uk |
Study information
| Study design | Observational qualitative study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Qualitative research |
| Study setting(s) | Other |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | The BLAST OFF (Bisphosphonate aLternAtive regimenS for the prevenTion of Osteoporotic Fragility Fractures) study |
| Study acronym | BLAST OFF |
| Study objectives | Comparing alternative regimens of bisphosphonates to the standard regimen of oral Alendronate, in preventing osteoporotic fracture in adults, the main research questions are: - Which bisphosphonate regimen is most effective at preventing osteoporotic fragility fractures with inclusion of reported side-effect profiles? - Which bisphosphonate regimen provides best value for money in terms of efficiency and cost using a health economic model? The aims are to: - Understand patient, clinician and researcher views, experiences and preferences in regards to adherence to different bisphosphonate regimens - Co-produce prioritised research questions to inform future research in this area |
| Ethics approval(s) | Approved 23/12/2019, North West - Preston Research Ethics Committee (Barlow House, 3rd floor, 4 Minshull Street, Manchester, M1 3DZ; +44 (0)207 1048197; nrescommittee.northwest-preston@nhs.net), ref: 19/NW/0714 |
| Health condition(s) or problem(s) studied | Osteoporotic fragility fractures |
| Intervention | The study will be completed in 3 stages. Stage 1A will update a systematic review to inform which regimens are most effective at reducing fractures and provide the best value for money. Stage 1B will consist of qualitative semi-structured interviews from a sample of stakeholders in receipt of or involved in the delivery of different bisphosphonate regimens, in order to identify which regimens are most acceptable to patients. Stage 2 will use focus groups and workshops to discuss uncertainties from Stage 1 and identify the most important outstanding questions for future research. This ethical review and information provided relates to Stage 1B. Stage 1A does not involve participants so does not require ethical review. Stage 2 will be conducted by the Royal Osteoporosis Society. Participants will not be invited via NHS organisations and no identifiable information will be collected. Use of the Health Research Authority decision tool identifies Stage 2 does not require ethical review. Participants are only involved in Stage 1B of the study, which consists of qualitative interviews only. Participants will be drawn from several different areas of healthcare, in order to ensure a best range of relevant patients’, clinicians’, commissioners’, service managers’ and researchers’ experiences. Patient participants will be identified as potentially eligible by their healthcare providers, either via their GP surgery or secondary care clinician. Patients will receive a Study Information Pack via the post, containing an Invitation (Patient) Letter from their GP or responsible secondary care doctor, a Participant (Patient) Information Sheet, a reply slip and a freepost envelope with the Research Team’s return address. This information pack will also include the Research Team’s contact details in order that potential participants have an opportunity to ask questions before indicating an interest in taking part in the study. Patients may also contact the Research Team to express interest by response to a Patient Information Poster in certain service areas, and they will be supplied with the same Study Information Pack. Patients who return a reply slip will be contacted by a member of the Research Team to arrange a convenient time and location in which to obtain written informed consent and undertake the semi-structured interview, which is likely to be immediately after written consent is obtained. Non-patient participants will be identified as potentially eligible via their General Practice Managers or via snowball sampling from their Service Lead in secondary care services. They will be provided with an Invitation (Clinician) Letter/Email and Participant (Clinician) Information Sheet. The information pack will also include the Research Team’s contact details in order that potential participants have an opportunity to ask questions before indicating an interest in taking part in the study. If they indicate to the Research Team they would like to participate in the study, a member of the Research Team will contact the participant to obtain written informed consent, before arranging a convenient time and location to undertake the semi-structured interview, which may be immediately after written consent is obtained. The semi-structured interviews will be conducted face-to-face or by telephone and are expected to take 40-50 minutes to complete. Face-to-face interviews will be conducted in a private setting either within the site of treatment or at their home in the case of a patient participant, or within the place of work for non-patient participants. The interview guide will be developed iteratively throughout the study to cover issues as identified from the scoping review of published studies assessing experiences of bisphosphonate regimens, as well as wider experiences of service quality and delivery. This will include questions around patient factors (such as values and health beliefs), service factors (location, accessibility, assurance, and empathy), relational factors (provider patient relations) and medication factors (dosing complexity, frequency, side effects). Clinician interviews will also include barriers to maintain a service around alternative bisphosphonates regimens, as well as changes in service over time. Interviews will be undertaken by qualitative researchers (employed by University of Nottingham). Interviews will be audio-recorded and then transcribed by Clayton Research Support, a Nottingham University Hospitals and University of Nottingham approved transcription service. There is no intervention involved in this study. Once the interview is completed, a participant’s involvement in the study is ended. There is no further follow-up. Thematic analysis of interview data will be conducted. This will involve familiarisation, identification of a framework, and interpretation, paying particular attention to themes clustered around service variables. The analysis will involve a preliminary phase of more general qualitative data analysis (close reading of transcripts, open coding, identification of themes). Analysis will be undertaken in the first instance by the Research Fellow alongside and overseen by the Stage 1B Lead. Emerging themes (with all identifying information removed) will be discussed at appropriate intervals with the wider study management group. The approach will allow for both a-priori and emergent codes to be identified. NVivo software will be used to develop an appropriate coding strategy and framework. |
| Intervention type | Other |
| Primary outcome measure | Views, experiences and preferences of patients, clinicians and researchers regarding different bisphosphonate treatment regimens collected through conduction and analysis of semi-structured interviews. |
| Secondary outcome measures | 1. Effectiveness of different bisphosphonate regimens in preventing fragility fractures in adults by analysis of published literature by systematic review 2. Cost-effectiveness of different bisphosphonate regimens in preventing fragility fractures in adults using a health economic model on data of published literature identified by systematic review 3. Prioritised future research questions regarding the effectiveness and adherence profile of different bisphosphonate regimens in preventing fragility fractures in adults by stakeholder engagement workshops using the James Lind methodology |
| Overall study start date | 01/09/2019 |
| Completion date | 30/04/2022 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 70; UK Sample Size: 70 |
| Total final enrolment | 100 |
| Key inclusion criteria | 1. Adults over the age of 18 with the ability to give informed consent Participants will need to come from one of the following stakeholder groups: 2. GPs 3. Patients who started on oral bisphosphonates within the last 24 months for prevention of fragility fractures 4. Secondary care specialist clinicians (nurses, consultants) involved in the treatment of osteoporosis 5. Patients receiving hospital based (intravenous) bisphosphonate treatments for prevention of fragility fractures who began treatment within the last 24 months 6. Clinical academics involved in osteoporosis research 7. Specialist clinicians (nurses, consultants) from the osteoporosis service in Nottingham and Sheffield with insight into alternate bisphosphonate treatments 8. Patients receiving alternate bisphosphonate treatments for prevention of fragility fractures who began treatment within the last 24 months 9. Commissioners involved in osteoporosis services |
| Key exclusion criteria | 1. Patients who take bisphosphonate medicines for reasons other than osteoporosis or osteopenia, including patients with an active cancer, primary hyperparathyroidism and Paget’s disease 2. Considered to be near to end of life |
| Date of first enrolment | 01/03/2020 |
| Date of final enrolment | 01/09/2021 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
Nottingham
NG7 2UH
United Kingdom
Herries Road
Sheffield
S5 7AU
United Kingdom
Derby
DE22 3NE
United Kingdom
Mindelsohn Way
Birmingham
B15 2TH
United Kingdom
Lincoln
LN2 4AX
United Kingdom
Stoke-on-Trent
ST4 6QG
United Kingdom
Somerset
BA2 0PJ
United Kingdom
Sponsor information
Hospital/treatment centre
Research & Innovation
C Floor, South Block
Queens Medical Centre
Derby Road
Nottingham
NG7 2UH
England
United Kingdom
| Phone | +44 (0)115 9709049 |
|---|---|
| researchsponsor@nuh.nhs.uk | |
| Website | http://www.nuh.nhs.uk/ |
"ROR" |
https://ror.org/05y3qh794 |
Funders
Funder type
Government
No information available
Government organisation / National government
- Alternative name(s)
- National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 30/08/2022 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not expected to be made available |
| Publication and dissemination plan | - Planned publication in high-impact peer reviewed journals such as British Medical Journal (BMJ), Osteoporosis International, Journal of Bone and Mineral Research (JBMR) and other appropriate high-impact specialist health economic journals. - Established CRN and NIHR network dissemination. - Dissemination to policy makers, commissioners, operational managers, change agents, healthcare professionals and patients/public led by links with the Royal Osteoporosis Society. - Study protocol available from study contact upon reasonable request - Stage 1B scoping review registered on Prospero (registration number CRD42019143526) |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are not expected to be made available due to participant confidentiality. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | 02/04/2022 | 26/04/2022 | Yes | No | |
| Results article | 02/11/2022 | 21/04/2023 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No | ||
| Results article | Acceptability and effectiveness | 01/04/2024 | 22/04/2024 | Yes | No |
Editorial Notes
22/04/2024: Publication reference added.
21/04/2023: Publication reference and ClinicalTrials.gov number added.
26/04/2022: Publication reference added.
25/04/2022: Total final enrolment added. Royal Osteoporosis Society Network was added as a trial participating centre.
10/03/2021: The following changes were made to the trial record:
1. The recruitment end date was changed from 01/03/2021 to 01/09/2021.
2. The overall end date was changed from 31/10/2021 to 30/04/2022.
3. The intention to publish date was changed from 30/08/2021 to 30/08/2022.
4. The plain English summary was updated to reflect these changes.
10/03/2020: The following changes have been made:
1. The recruitment start date has been changed from 06/01/2019 to 01/03/2020.
2. The recruitment end date has been changed from 06/01/2020 to 01/03/2021.
30/12/2019: Trial’s existence confirmed by National Institute for Health Research (NIHR)
