Some text in this chapter has been reproduced from Bastounis A, et al. Osteoporos Int 2022;33:1223–3. This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) licence, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See https://creativecommons.org/licenses/by/4.0/. The text below includes minor additions and formatting changes to the original text.
Introduction
In order to enhance adherence to BP, and thus contribute to addressing the osteoporosis care gap, it is important to understand perspectives of all relevant stakeholders in using these drugs. There are many possible research agendas to pursue and, traditionally, researchers have identified health research priorities. However, PPI in research, including the prioritisation of research agendas, is now well established.185–191 Involving patients and the public ensures that research is grounded in patient relevance, research questions are meaningful and important research topics are identified that researchers may not have previously considered.192 Over the last decade, a number of initiatives, such as INVOLVE, part of the NIHR, have been established to facilitate and promote active public involvement in all aspects of research, including priority setting. The James Lind Alliance (JLA) was formed in 2004 and aimed to bring patients and clinicians together in a new way to identify and address important uncertainties about the effects of care and treatments.193
Despite the apparent revolution in patient engagement, evidence suggests the mismatch between the research that is conducted and the research patients want still persists. A previous report commissioned by the JLA established that the majority of charitable funders in the UK funded research in a responsive mode, with only a minority funding research that met pre-identified priorities.194 With respect to BP as a treatment for osteoporosis, no studies have investigated the research priorities of stakeholders. Paskins et al. (2017) conducted the first national study of public and patient research priorities in osteoporosis and fracture.195 Participants were asked to indicate their top priority for research across 40 different research items. Understanding the safety and benefit of osteoporosis drug treatments was identified as the second priority research area. However, a need was identified for more refinement to translate this research focus into specific research questions. This paper aims to address this gap by conducting a research prioritisation exercise to understand priorities relating to BP treatment regimens for prevention of osteoporotic fractures in adults.
Methods
We used a three-step approach based on the JLA methodology for identification and prioritisation of research questions.196 An overview of the methods is shown in . This prioritisation study did not require ethics approval as per the JLA guidance.
Step 1: gathering uncertainties
Uncertainties were gathered from (1) Chapters 2–5 and (2) existing published research recommendations. Over a series of four group meetings, the group study team reviewed and discussed the findings from (1) Chapters 2–5 and generated a list of potential arising uncertainties. A final meeting involved a patient advisory group (PAG) to further inform the process. Separately, a systematic search of relevant electronic databases and websites of professional organisations was conducted to identify (2) research recommendations highlighted within recent clinical guidelines. Databases searched included Epistemonikos, NICE, SIGN, Guidelines international network, Guidelines.co.uk and TRIP database. Inclusion criteria were (1) international guidelines from non-low- or middle-income country (LMIC), (2) about osteoporosis (including glucocorticoid osteoporosis), (3) published since 2016 and (4) developed on behalf of a professional organisation. Exclusion criteria were: (1) guidelines from LMIC, (2) about osteoporosis only in the context of another specific health condition, (3) published before 2016 and (4) written by individuals not representing a broader organisation. Attempts were made to translate guidelines that were not in the English language. Relevant sections on recommendations for research were extracted, and a list of research recommendations was produced. Subsequently, research recommendations were considered as in- or out-of-scope initially by two members of the study team (ZP, NC) and then approved by the whole team, with in-scope recommendations defined as relating to the use of BP. This generated a list of research recommendations.
Step 2: processing and refining uncertainties
Using stakeholder input, we refined the list of uncertainties from (1) and research recommendations (2) into research questions. One 3-hour stakeholder meeting was convened with patients and carers, clinicians (medical and non-medical) and academics to include representatives from primary and secondary care. Potential participants were invited from the ROS Effectiveness Working Group of the Bone Research Academy, Nottingham osteoporosis patient support group and clinical networks of the study team. We recorded the professional role and sex of attendees, but we did not collect data on age or ethnicity. The list of uncertainties and list of research recommendations [outputs from (1) and (2)] were circulated to attendees before the meeting. In the meeting, within small groups, the list of uncertainties were discussed and refined, with some uncertainties combined as appropriate. Attendees and study team members had the opportunity to suggest additional uncertainties during this process. The uncertainties were also categorised into groups. Each uncertainty was then refined into a research question with particular attention to defining the population and setting, intervention, comparison and outcomes of interest.197 These were then combined with (2) forming a final list of research questions (3).
In order to validate that the research questions (3) were true research questions and not already answered, a search was subsequently conducted of the Cochrane Database of Systematic Reviews, PubMed and references of NICE guidelines, SIGN clinical guidelines, NOGG guidelines and ROS guidance for any relevant systematic reviews. If no systematic review was found to exist, the research question proceeded to Step 3.
Step 3: prioritisation
A full-day online workshop was convened in February 2022, aiming for between 12 and 30 participants to include a mix of patients, carers and primary and secondary care clinicians. Potential participants were invited as per the Step 2 workshop; in addition, the workshop was advertised on Twitter and via the Keele research User Group to particularly target lay, non-medical and primary care representatives. People were allocated on a first-come, first-served basis with the aim of achieving a balance of attendees across professional and lay groups. Study team members attended and acted as facilitators but did not vote or discuss ranking. Information on participant interests and disclosures was collected and reviewed to ensure balance across the group. Participants were sent the research questions in advance and asked to rank their top twenty questions before the workshop. Participants were permitted to send in pre-ranking if interested but unable to attend the workshop. In the workshop, an adapted nominal group technique was used. As per updated JLA guidance for online workshops, a four-step approach was used (removing a fifth plenary step, which has been difficult to operationalise online).198 The workshop started with a plenary session to introduce the task and explain the background. Thereafter, four small groups compared and discussed their initial pre-workshop rankings. After a break, the same groups then produced their own combined ranking of at least the top 20 questions. The ranking of the four small groups was then combined and shared with the group in a plenary session. Finally, a second round of group prioritisation took place, to revise the shared ranking, in new small groups. These small group rankings were combined, reviewed and agreed as the final prioritised list.
Patient and public involvement
Members of the Nottingham ROS (NotROS) Support Group were involved in a series of meetings to discuss the design of the BLAST-OFF research programme and confirmed that understanding acceptability of BP from a range of perspectives was important. A PAG helped the study team identify the research uncertainties emerging from BLAST-OFF and public contributors were involved in both stakeholder groups (Steps 2 and 3).
Results
Step 1: gathering uncertainties
The study team and PAG identified 22 uncertainties. Eleven uncertainties were informed by Chapter 2, 9 by Chapter 3, 11 by Chapter 4 and 7 by Chapter 5. The PAG talked about the importance of outcomes other than fracture, for example, meeting people’s information needs. They discussed and particularly informed uncertainties relating to how patients could be supported to make decisions, how treatment could be made easier and how effectiveness could be monitored.
Sixty-nine potential clinical guidelines were identified, of which 17 included relevant research recommendations ().
Search for clinical guidelines results.
Sixteen research recommendations were informed from the clinical guidelines; six of these overlapped with uncertainties from our study. In addition, the clinical guideline research recommendations highlighted populations in need of specific study, including men, people without BMD-defined osteoporosis, frail older adults, those with cognitive impairment and those with glucocorticoid-induced osteoporosis.
Step 2: processing and refining uncertainties
Eleven people attended Workshop 1. Characteristics of those attending are listed in Table 17.
Characteristics of workshop attendees
The group was asked to consider the specific populations highlighted in the research recommendations when rewording and refining all the research uncertainties; younger adults emerged as a further group from discussion where further research was needed. Following the workshop, the uncertainties and research recommendations were finalised into 33 distinct research questions.
Step 3: prioritisation
Thirty-three questions went forward for prioritisation, organised into five categories relating to patient factors and patient support; clinical support and policy; safety; effectiveness and delivery. Twenty people attended Workshop 2, with a further individual (a GP) submitting individual rankings for consideration in the first small group work without attending. Characteristics of attendees were similar to those shown in Table 17.
The final top 10 priorities are shown in Box 1. Research questions 11–20 were also ranked, with the remainder unranked (attached in Appendices 6 and 7, Boxes 2–3).
Finalised top 10 research priorities
Discussion
This chapter reports, for the first time, topics of importance to stakeholders in the research of BP treatment regimens for the prevention of osteoporotic fracture in adults, refining previously identified priority areas into specific questions. We identified a number of previously undescribed priority areas relating to BP regimens for people with osteoporosis, including research into the best regimen for people aged under 50 and research comparing the safety, clinical and cost-effectiveness of IV treatment given in peoples’ homes versus hospitals. Furthermore, there was also a particular call to research patient factors influencing treatment selection and effectiveness, highlighting the importance of this research being underpinned by the ethos of personalised care.
The top research priority ‘Which people with osteoporosis should be offered IV BP first line to optimise medicine effectiveness?’ could be influenced by a range of different patient factors, which, in turn, would influence treatment selection and effectiveness. Patients are typically not given a choice between oral or IV BP. While clinicians may choose to offer IN BP on the basis of tolerability and safety issues, more empirical evidence is needed which specifically investigates which patients would benefit most from first-line IV treatment. Published research recommendations and previous prioritisation exercises largely focus on safety and optimal duration of drug treatment,199–201 both of which were included within the top 10 research priorities identified in this study. However, the top 10 list also highlights the importance of developing a long-term model of care, providing more support for ongoing medicine optimisation and researching the role of monitoring (bone turnover markers). These areas have been highlighted in a recent rapid realist review exploring the effective characteristics of interventions to support medicine optimisation in osteoporosis, which identified a need for a person-centred model of long-term care for osteoporosis;202 interestingly, this review also highlighted the need and role of providing primary care practitioners with decisional support to improve patient outcomes – also highlighted in our top 10. The question relating to ensuring quality standards are met highlights the importance of knowledge mobilisation and applied health services research, which addresses barriers to implementation of clinical guidelines.
The previous prioritisation exercise in this area identified that ‘having easy access to advice and information from health professionals’ was the highest rating research priority. This top 10 includes the more specific question ‘supporting people with osteoporosis to make decisions about taking BP’. Our preceding qualitative research identified that people reported the benefits of BP to be ambiguous; previous research studies have investigated the role of decision support in osteoporosis, and ongoing development work and trials will hopefully provide further evidence to support this area over the coming years.203,204
Our findings highlight the importance of conducting priority-setting exercises which involve all stakeholders and to not solely focus on guideline recommendations. Of the top 10 identified research priorities in this study, only 3 were derived from guideline recommendations (research priorities 3, 4 and 8). Particularly novel questions relate to the use of ZOL in the community and the best BP regimen for young adults. Research has shown that the majority of guidelines do not include the views of public and patients205 and, when mentioned, their views were only conceptualised as preferences for one medication over another.
Strengths and limitations
While the study provided some important insights, it is subject to some limitations. Patient and caregiver responses within the workshops may have been influenced by the presence of HCPs. Furthermore, the stakeholders involved might not be entirely representative of the wider population. The study may not have adequately represented underserved populations, and stakeholders’ ethnicity data were not collected; this may have affected the final questions prioritised. Employing survey methods may have identified a more representative sample of stakeholders; however, qualitative research to inform priority setting is well-established and useful. The strengths of the study included the comprehensive guideline search, which ensured existing, relevant and published research recommendations were included and discussed when gathering uncertainties to discuss within the workshops. The depth of research in the BLAST-OFF study was also a strength, particularly the qualitative interview study, which included in-depth, rich descriptions from 78 patients receiving BP regimens.
Conclusions
In summary, this prioritisation exercise highlights the importance of including stakeholders when setting research priorities and provides a more in-depth understanding of the priorities of stakeholders in BP regimens. While some research priorities, such as supporting people with osteoporosis to make decisions about their treatment, are being addressed, the findings illustrate a need for further research to address the issues relating to patient factors influencing treatment selection and effectiveness and how to optimise long-term care. In addition, these findings have implications for research into implementation to address the care gap and education of HCPs.
