Aims and objectives
- To explore the attitudes and perceptions of patients towards the roles of the pharmacist, general practitioner and dentist in the prevention of Bisphosphonate Related Osteonecrosis of the Jaw (BRONJ).
- To explore the barriers or enablers to optimising the risk prevention of BRONJ
- To explore the attitudes and perceptions of patients about their broader priorities during counselling on medication
Benefits to patients
A diagnosis of BRONJ can have serious implications for patients. Current guidelines (SDCEP 2011, AAOMS 2014) recommend that preventative measures, such as dental screening and appropriate dental treatment before initiation with bisphosphonates should be the focus of the multidisciplinary team, however the roles of team members from the perspectives of patients are not understood. This project will explore patients’ attitude and perceptions towards the multidisciplinary approach to the prevention of BRONJ.
We will highlight areas of care, which from the patient’s perspective, can be improved in order to prevent BRONJ. This understanding will help to inform healthcare professionals’ practise of this patient group on ways that care can be optimised.
Current estimates suggest that there are 620 new cases of BRONJ per year in the UK. With an aging population and increased exposure of susceptible elderly patients to the potential risk of BRONJ, the development of initiatives or services that will reduce the number of cases of BRONJ will have a significant impact on this group of patients.
Results may be used to aid the development of pharmacy services or to further expand services already in existence. For example the New Medicines Service does not currently target bisphosphonates, if evidence emerges from the data that this would be of benefit to patients, the results from the study may be used to support such a case.
Background
Bisphosphonates are a class of drugs that are widely used for a number of indications. In practice they are most commonly prescribed in osteoporosis, although they can be used to treat Paget’s disease, hypercalcaemia of malignancy, osteolytic bone metastases and osteolytic lesions of multiple myeloma (Fliefel et al 2015).
The prescribing of bisphosphonates has increased considerably over recent years. Prescription statistics for England show a rise of 122.6% in the number of items dispensed between 2004 and 2014, with alendronic acid being the most prescribed item with 7,391,000 items dispensed in 2014 (Health and Social Care Information Centre 2015). This rise is likely due to an increase in an ageing population which is set to continue.
Case reports began to emerge in 2003 associating bisphosphonate therapy with the development of osteonecrosis of the jaw. Subsequently a number of MHRA and EMA Alerts have been released highlighting this issue (MHRA 2009, EMA 2009).
The incidence of BRONJ is difficult to quantify with varying reports in the literature, this is likely due to the low incidence of reporting, the variance in diagnostic criteria and some mild self-resolving cases going unidentified.
The incidence rates reported vary from 0.7/100,000 prescribed patient years to 0.34% in population studies, with incidence rates of up to 10% reported in certain patient groups, such as patient prescribed IV bisphosphonates for myeloma (Patel et al 2011).
Consistently, throughout the literature the diagnosis of osteonecrosis of the jaw is associated predominately with intravenous bisphosphonate therapy. A recent meta-analysis of the incidence of BRONJ found the overall occurrence rate to be 3.2% in cancer patients being treated with IV bisphosphonates and 0.15% in patients administered oral bisphosphonates for osteoporosis (Gaudin et al 2015).
A multi-centre retrospective study reviewed clinical data from patients (n=470) diagnosed with BRONJ over a four year period (2004-2008). The majority of patients (90.5%) reviewed in the study were prescribed bisphosphonates due to malignancy, 7.8% of patients were prescribed oral bisphosphonates for the treatment of osteoporosis (Otto et al 2011).
The Faculty of General Dental Practice (UK) in 2012 suggest that if estimates for the incidence of BRONJ were applied to the current UK population of 62 million it would indicate a total of 620 new (508-793) BRONJ cases a year (Faculty of General Dental Practitioners 2012). Although the literature points to a significantly greater association between intravenous bisphosphonate therapy and osteonecrosis of the jaw, the links to oral bisphosphonate therapy cannot be discounted.
Osteonecrosis is death of bone tissue. Clinically osteonecrosis of the jaw presents as exposed alveolar bone. The site is usually painful with soft tissue swelling or ulceration and mobile teeth (Otomo-Corgel J 2012) Osteonecrosis of the jaw is a condition where there is delayed healing of the jaw that results in unhealed areas and the exposure of underlying jaw bone for longer than would be expected. The majority of reported cases are associated with dental infection or invasive dental procedures, including tooth extractions (National Osteoporosis Society 2014).
Although the prevalence of BRONJ is low the significance and morbidity associated with a diagnosis to the patient cannot be underestimated. In patients diagnosed with BRONJ the aims of treatment are to eliminate clinical symptoms such as pain, minimise progression of bone necrosis and treat infections of the bone or soft tissues. Surgical management aims to remove necrotic bone, with radical surgical management for patients with large segments of necrotic bone or pathological bone fractures. The difficulties in treating BRONJ illustrated in the literature highlight the importance of preventative measures (McLeod 2012).
Bisphosphonate related osteonecrosis of the jaw (BRONJ) is thought to be related to the unique nature of the blood supply, structure, function and microbiology of the jawbones. Jaw bones have a high blood supply which may result in an increased concentration of bisphosphonates in this area and bone turnover is also thought to be high due to forces related to chewing and the presence of teeth (European Medicines Agency 2009) The alveolar crest remodels at 10 times the rate of the tibia and uptake and concentration of bisphosphonates is higher in the alveolar bone compared with other sites (Otomo-Corgel J 2012).
Bisphosphonates exert their effect on osteoclasts when they resorb bone as part of its normal metabolic turnover. The inhibition of osteoclasts, depression of angiogenesis and modification of blood vessels in the mandible and maxilla may lead to avascular bone necrosis in the jaw. Trauma can lead to microfractures and with the possibility of infection require repair, if the bone is not repaired properly localised osteonecrosis can occur (Shannon et al 2011).
The underlying mechanisms of BRONJ are not yet fully understood; however, what is well established is the association with poor dental health. Therefore it is for this reason that preventative measures are of upmost importance, with dental and medical practitioners working collaboratively (Rayman et al 2009).
Ideally optimal dental health should be established before the patient commences therapy. (Otomo-Corgel J, 2012). Scottish guidelines recommend that before commencement of bisphosphonate therapy or as soon as possible, the aim should be to get the patient as dentally fit as feasible, prioritising care that will reduce mucosal trauma or may help avoid subsequent extractions or any oral surgery or procedure that may impact on bone (Scottish Dental Clinical Effectiveness Programme, 2011).
Due to the risk factors for developing osteonecrosis of the jaw with bisphosphonate therapy, dental clinicians should work closely with medical colleagues before prescribing (Otomo-Corgel J 2012).
A multidisciplinary approach to the prevention of BRONJ is recommended in the management of patients requiring bisphosphonate therapy (Shannon et al 2011 (Patel et al 2011), with both patient and health professional education about the risks of developing BRONJ (European Medicines Agency 2009). With education of dentists, pharmacist, medical practitioners and patients about BRONJ (Rayman et al 2009) with the emphasis on providing more preventative measures and oral hygiene instructions (Gaudin et al 2015).
The European Medicines Agency specified a number of key messages that should be communicated to healthcare professionals and to patients advising that the risk of osteonecrosis of the jaw with oral bisphosphonates appears to be low compared to patients receiving IV bisphosphonates for cancer indications, however risk factors should be considered when judging and individual’s risk of developing BRONJ. Their advice is that dental check-ups prior to treatment should be carried out in all patients for cancer indication but only for those with poor dental status for non-cancer indications. They do advise that patients should maintain good oral hygiene and receive routine dental check-ups (European Medicines Agency 2009).
The involvement of the multidisciplinary team is established in the prevention of BRONJ. However, there is limited evidence in the literature to identify the extent of knowledge of patients, general medical practitioners and pharmacists surrounding the risks and prevention strategies associated with the development of BRONJ. An ongoing MSc project by the principle investigator is already researching the issue in relation to both pharmacist and general practitioners; this is expected to be completed by August 2016. Early results indicate that patients are not afforded the opportunity to discuss risk associated with this treatment, which in turn has led to the development of this proposal.
This proposal will build on the applicants Masters project and seeks to gain an insight into the attitudes and perceptions of patients towards osteonecrosis of the jaw, a rare but potentially significant adverse effect of bisphosphonate drugs. Guidelines recommend that a multidisciplinary approach to prevention should be adopted; however the perceived role of the pharmacist, general practitioner and dentist by the patient is unknown. The aim of this study is to illuminate the perceptions of patients and also look to explore any barriers or enablers that can optimise the risk prevention of this group of patients.
Although the incidence of BRONJ is low, with estimates of 620 new cases per year in the UK (Faculty of General Dental Practitioners 2012), the implications for the patient cannot be underestimated. A review of the literature has been performed though an extensive search of electronic databases, such as PubMed, Discover and Google Scholar, the limited quality and quantity of research suggests that the knowledge of the dental risks associated with bisphosphonates is low amongst general medical practitioners, pharmacists and patients. Studies have already identified this to be the case; however it appears that deeper research to identify the underlying issues associated with this lack of awareness has not been carried out.
A small quantitative study of general medical practitioners (n=120) and pharmacists (n= 60) in North Wales identified that although both sets of healthcare professionals have regular contact with patients prescribed bisphosphonates they had limited knowledge of the dental implications associated with treatment. Both sets of healthcare professionals reported good awareness of the side effects of bisphosphonates, however only 11.8% of GMP and 0% or pharmacists specifically identified osteonecrosis (Masson et al 2009).
Another small quantitative study (n=55) found that the majority of patients acquired knowledge about the drug they were prescribed from the patient information leaflets (62%) with few patients (13%) receiving this information from their general practitioner. When asked to identify which side effects of bisphosphonate therapy they were aware of, only 32% of patients receiving IV and 17% patients receiving oral bisphosphonates identified osteonecrosis of the jaw (Bauer et al 2012).
Ongoing research
A qualitative research project that forms the research project element of an MSc in Clinical Pharmacy for the principle researcher is currently underway. This project is seeking to illuminate the attitudes and perceptions of general practitioners and pharmacist towards the risk and prevention of BRONJ.
This project has followed similar methodology to that proposed in this grant application. The proposed project will differ in that it builds on the work being carried out by bringing the patient into the research and aims to explore their attitudes and perceptions to the multidisciplinary approach to the prevention of BRONJ.
How will results be used?
Through a deeper understanding of the patient’s attitudes and perceptions towards the multidisciplinary approach to the prevention of BRONJ, this information may provide guidance to health care professionals and healthcare policy makers. Provide evidence to support the development of new initiatives that could be implemented to reduce the risk of patients developing BRONJ. It is also anticipated that this research will produce findings that go deeper than the original research question, exploring patient’s perceptions on counselling on medication, risk factors and the roles and responsibilities of members of the multidisciplinary team.
Plan of investigation
Study Design
Qualitative methodologies have been selected for this study. Qualitative research generally aims to provide an in-depth and interpreted understanding of the social world of the research participants, their experiences, perspectives and histories (Ritchie et al 2013).
Previous quantitative studies examining the extent of knowledge of BRONJ amongst patient have sought to find metrics to explain the phenomenon. Although the literature is limited, only 11.8% of GMPs and 9.7% of pharmacists advised patients to warn their dentist they were using bisphosphonates (Masson et al 2009). A small quantitative study (n=55) found that the majority of patients acquired knowledge about the drug they were prescribed from the patient information leaflets (62%) with few patients (13%) receiving this information from their general practitioner. When asked to identify which side effects of bisphosphonate therapy they were aware of, only (32%) of patients receiving IV and (17%) patient receiving oral bisphosphonates identified osteonecrosis of the jaw (Bauer 2012). What is not clear from this research are the underlying attitudes and perceptions of patients towards the risk and prevention of BRONJ that relate to and can explain the quantitative findings above. In-depth qualitative interviews are required to deliver the aims and objectives of this study, in that the research question seeks to explore the perceptions of participants, their attitudes and behaviours.
What is already apparent from the literature is the lack of knowledge on the subject from patients, a deductive approach to research would look to apply this knowledge, make observations of participants and look to strengthen this theory. However, it is the underlying perceptions of patients that are linked to the objectives of this study, therefore an inductive approach, building knowledge from the bottom upwards with observations, will be used to provide the basis for generating a theory that explains the phenomenon.
Data collection will be carried out by a series of face-to-face, semi-structured, in-depth interviews. A ‘Grounded Theory’ approach will be used in the study, with concurrent collection and analysis of qualitative data and constant comparison between participants. The emergence of themes during the process provides the opportunity for further exploration with subsequent data collection, aiming to achieve saturation of the data.
The NIHR Research Design Service was consulted in the planning of this study.
The principle researcher met with a patient representative from the University of Sunderland patient involvement group to discuss this study. The patient felt like in depth interviews would give the opportunity to explore topics in detail and felt comfortable discussing issues in this manner. He felt like questionnaires often don’t give him the opportunity to explain himself and the responses available don’t always match his thoughts. He also felt that the opportunity to discuss the findings with other participants would be useful and may raise points that he would not have thought about individually.
Phase One
Participants and Sampling
This project will be entered on the National Institute for Health Research (NIHR) portfolio and patients will be recruited via the Clinical Research Network, North East and North Cumbria (CRN: NE&NC), specifically with the assistance of the primary care specialty group led by Prof. Scott Wilkes and clinical pharmacy champion, Ms Gemma Donovan.
Purposive sampling will be used to recruit participants to give an initial diverse sample. Theoretical sampling will then follow to inform the categories and themes developing through concurrent data analysis and collection. Interviews will continue until data saturation has been reached with an anticipated 15 to 20.
An initial maximum variation sample will be recruited from the following categories:
- Patients with a diagnosis of BRONJ – recruitment through the NIHR portfolio and Newcastle Dental Hospital. Patients will be identified through the local dental hospital with the support of the dental specialty group of the NIHR CRN: NE&NC.
- Patients prescribed oral bisphosphonates – recruitment through community pharmacies and GP practices. Patients will be identified in GP surgeries and community pharmacies with the help of the NIHR CRN: NE&NC Primary Care Specialty Group and Pharmacy Champion.
- Patients with osteoporosis – recruitment through community pharmacies and GP practices. Patients will be identified in GP surgeries and community pharmacies with the help of the NIHR CRN: NE&NC Primary Care Specialty Group and Pharmacy Champion.
Interview process
Participants will be interviewed in detail by the researcher; interviews will take up to one hour.
They will be recorded and transcribed verbatim. Prior to the interview participants will receive a participant information sheet, sign a consent form and some provide some baseline demographic information.
The use of interviews with the assistance of an interview guide will allow for some consistency over the concepts to be covered. However, flexibility in the interview process will give the researcher and interviewee the opportunity to explore new topics or concepts that develop during the interview, as per grounded theory.
Ethics approval will be sought from both the University of Sunderland and the NHS through the Integrated Research Application System (IRAS). Interview transcripts and analysis will be non-identifiable; a list of participants will be kept by the researcher on a password projected file at the University of Sunderland, signed consent forms will be held by the researcher in a locked cabinet. Access to data will be limited to the researcher, project supervisor and any persons approved by the University Ethics Committee for quality assurance purposes. Further details on ethical issue are discussed in section M, risk management.
Analysis
The ‘Framework’ model of qualitative data analysis was developed in the UK, by the National Centre for Social Research (Ritchie and Spencer 1994). It provides a systematic and practical approach to the analysis of qualitative data. It has grown in popularity and is becoming an increasingly popular approach in the analysis of qualitative data amongst health researchers (Gale et al. 2013).
Framework analysis has been chosen as it provides a straight forward, transparent (Ward et al 2013) and structured approach to the analysis of qualitative data (Gale et al. 2013).
The Framework model follows a five-stage approach to the analysis of qualitative data (Ritchie and Spencer 2002).
Familiarisation
Familiarisation occurs through immersion in the raw data. This is through the process of data collection, listening to audio recordings and the detailed reading of the transcripts and field notes. Following this, key ideas and notes on the recurrent themes will be produced.
Identifying a thematic framework
Following familiarisation with the data, the key issues and themes that have been identified form the basis of a thematic framework. This is carried out through a deductive process drawing on a priori issues that form the aims of the study as well as issues raised by the participants that recur in the data. As a result, a detailed index of the data will be developed, thus allowing data to be labelled and explored.
Indexing
The thematic framework will be applied and all data contained in the transcripts indexed against the codes. This allows for the identification of portions or sections of the data that correspond to a particular theme or concept in the thematic framework.
Charting
The data that has been indexed will then be rearranged to form charts of the themes. Charts will be produced for key themes with entries from the data, linked to individual participants.
Mapping and interpretation
The charts produced will be used to guide the comparison of themes and subthemes. These will be checked against the original transcripts to ensure appropriate context. The associations and differences between the data and the emerging themes will be identified and used to provide explanations of the findings.
Phase Two
On completion of the individual interviews, all patients interviewed will be given the opportunity to attend a focus group. We anticipate that a sample of the expected 15-20 interviewees will agree to participate. The themes produced following the analysis of the individual interviews will form the basis for a focus group discussion and will be used to improve the validity of the findings and move towards consensus.
Sample: Patients who participated in the one-one interviews will be invited to attend the focus group
Recruitment: Participants will be asked if they would like to take part in the focus group following their individual interview.
Analysis: Data generated from focus groups will be transcribed verbatim and analysed using the framework approach.
Reflexivity
The role of the researcher will be considered in this qualitative study. The fact that the researchers own beliefs and behaviours can influence the research process leads to the term ‘reflexivity’. As a pharmacist, my attitudes towards the further development of the pharmacist’s role could potentially influence the study. Therefore, awareness of this has influenced the design of the study towards the more transparent and logical framework model for data analysis.
Supervision of the project by Scott Wilkes, Professor of Primary Care and General Practice, along with an experienced dental researcher, Professor Philp Preshaw and qualitative researcher Dr Catherine Hayes will ensure reliability and rigor in the investigation.
