The protocol is reported in accordance with the PRISMA-P statement (12) [see additional file 1] and has been registered with the International Prospective Register of Systematic Reviews (PROSPERO) registration number PROSPERO CRD42020196490.
Aim, design and setting:
The review aims to identify examine and explore factors associated with access to guideline recommended treatment with SACT for women with SBC. It will seek to determine those factors most commonly associated with access and treatment receipt, including those which present barriers and act as facilitators and those which are potentially most amenable to change.
The review will adopt a mixed methods approach applying a segregated design which will maintain the conventional binary distinction between the qualitative and quantitative paradigm, with integration of each distinct synthesis. The quantitative component aims to identify and investigate those multi-level factors associated with access and receipt of treatment (Table 1.). This will be complimented by the qualitative component which aims to explore how women with secondary breast cancer and their clinicians experience access and receipt of SACT. In particular, to explore barriers and facilitators related to individual, clinical and wider contextual factors relating to health care systems and geographical location. A mixed method approach will be taken as access to treatment is a complex, multi-faceted phenomena which requires a comprehensive, patient centred understanding of how and why and in what context any association exists. This is conducive to a more sophisticated integration of the traditional quantitative and qualitative paradigms offered by a mixed methods approach.
The review setting and context reflects the mixed method approach and will consider studies which explore multi-level factors which have previously been associated with access to treatment. The review will consider studies which investigate and explore access to SACT, including chemotherapy, targeted therapy, immunotherapy and hormone/endocrine therapy. This will include studies which report across secondary, tertiary, specialist and palliative care centres, where SACT is accessed as either, first, second or subsequent line of treatment.
Study eligibility:
The review will consider studies that include women aged 18 and over with an SBC diagnosis who have accessed and received (or otherwise) treatment for their disease with SACT. This will include studies reporting all clinical sub types of SBC and all sites of metastases. The study population will be consistent across quantitative and qualitative components.
Table 1
Multi-level factors associated with access and receipt of treatment.
Factors
|
Characteristics
|
Individual factors:
|
• Age, gender, sexual orientation
• Race/ethnicity
• Socioeconomic status
• Education
• Language and literacy
• Psychosocial characteristics
|
Clinical characteristics:
|
• Clinical sub type, including, Hormone receptor status, HER2 status
• Previous treatment response
• Physician characteristics
|
Contextual factors:
|
• Geography and geographical location, Including, distance, travel time, health region, catchment/referral areas
• Organisational Including, health care system factors, capacity, service availability
|
Studies reporting the primary outcome measure of access to and receipt of SACT as either, first, second or third line treatment for secondary breast cancer will be included. The review will be limited to studies published in peer reviewed journals which report original research in English language from January 2000 onwards. Quantitative studies will include observational studies, cross sectional, longitudinal and analytic studies, including, epidemiological studies, case control and cohort studies. RCTs reporting access and receipt will be included though where they report safety and efficacy alone, will be excluded. Qualitative studies will include designs such as phenomenology, grounded theory, ethnography, action research and feminist research. Descriptive qualitative studies that describe the experience or the effects of the experience will also be considered. Table 2 presents a summary of study inclusion and exclusion criteria.
Table 2
Summary of study inclusion and exclusion criteria.
|
Study inclusion criteria
|
Study exclusion criteria
|
Population:
|
Studies reporting on women aged 18 and over with a confirmed secondary breast cancer diagnosis who accessed treatment with a systemic anti-cancer therapy for their disease. This will include studies reporting all clinical sub types across all sites of metastases and will include de novo presentations.
|
Studies reporting on women with a primary diagnosis of early stage (I-III) breast cancer only
Studies reporting on women with a diagnosis of locally advanced breast cancer (LABC) with local or loco regional recurrence only
Studies measuring (comparative) treatment effect, efficacy and studies reporting clinical trials of systemic anti-cancer therapies, as whilst RCT is not a specific exclusion criteria, it is likely that RCTs will measure treatment effect as opposed to access as an outcome and would therefore be excluded.
Males with a secondary breast cancer diagnosis, as this is classified as a rare disease
|
Phenomena of interest:
|
Studies which explore factors that are associated with access to SACT for SBC.
|
|
Intervention/Exposure:
|
Studies reporting on access and receipt of systemic anti-cancer treatment at secondary, tertiary or specialist cancer centres and units. This will include a diverse range of health care organisations and systems.
|
|
Outcome(s):
|
Studies reporting the primary outcome measure of access to, and utilization of systemic anti-cancer therapies. This will include studies reporting access to chemotherapy, single agent or combination, hormone/endocrine therapy, targeted therapy and immunotherapy, as either, first, second or third line treatment, for secondary breast cancer.
|
Studies which do not report the primary outcome measure of access to, and utilization of systemic anti-cancer therapies
|
Types of study:
|
The review will consider quantitative, qualitative and mixed methods studies. This will include observational, cross sectional, longitudinal and analytic studies, including, epidemiological studies, case control and cohort studies.
Qualitative studies will include designs such as phenomenology, grounded theory, ethnography, action research and feminist research. Descriptive qualitative studies that describe the experience or describe the effects of the experience will also be considered. Mixed method studies will only be considered if data from the quantitative or qualitative components can be clearly extracted.
Studies published in English language, from January 2000 onwards, peer reviewed, original research, reporting quantitative, qualitative or mixed methods
|
Studies measuring (comparative) treatment effect, efficacy and studies reporting clinical trials of systemic anti-cancer therapies, as whilst RCT is not a specific exclusion criteria, it is likely that RCTs will measure treatment effect as opposed to access as an outcome and would therefore be excluded.
|
Search strategy and information sources:
A modified PICO framework was used to develop the review question (13). This was then used to formulate the search strategy by identifying key concepts, subject headings and keywords (Table 3). A preliminary search was undertaken to identify articles on the topic with text words in titles and abstracts of relevant articles. This was then used to develop a full search strategy. The search strategy including all identified keywords and index terms will be tailored to each information source. The electronic databases to be searched will be The Cochrane Library, EBSCO CINAHL Plus, Ovid MEDLINE, Ovid EMBASE, PsychINFO. Reference lists of included studies will also be screened. The basic search strategy will be tailored to individual databases and undertaken with the support of an experienced librarian/evidence specialist. Grey literature will be searched using NHS Evidence.
Table 3
Basic search strategy, key concepts and search terms.
PICO:
|
Population
|
Exposure
|
Outcome
|
Study design
|
Key concept:
|
Secondary breast cancer
|
Factors which influence access
|
Systemic anti-cancer therapies (guideline recommended)
|
Quantitative, qualitative, mixed methods
|
Subject headings and keywords:
|
Secondary OR advanced OR metastat*
Breast OR mammary
Cancer OR neoplasm OR tumour OR oncolog*
|
Factors:
sociodemographics OR socioeconomic
ethnicity OR race
education OR sexual orientation
psycho* (social)
geograph* OR location OR distance
clinical characteristics, hospital and physician characteristics
Access:
Access OR health care OR accessibility OR utilisation
|
Systemic OR anti-cancer OR therapy
Chemotherapy:
Chemotherap* OR antineoplastic agents, combined OR chemotherapy, cancer OR cancer drug OR drug therapy OR exp neoplasms/dt [drug therapy]
Hormone/endocrine therapy:
aromatase inhibitors OR tamoxifen OR hormone therapy OR oestrogens OR epidermal growth factors
Biological/targeted therapy:
Antibodies, monoclonal OR biological therapy OR methotrexate
Immunotherapy:
Immunotherapy
|
RCT, cohort study, observational study, case control study, epidemiological study, survey, case series
Phenomenology, ethnography, grounded theory, interview, focus group
Mixed methods
|
Study screening and selection:
Records will be stored and managed in EndNote X9. Titles and abstracts will be screened against the inclusion and exclusion criteria. Potentially eligible studies will be retrieved in full. Full text articles will then be assessed against the inclusion and exclusion criteria, with reasons for exclusion recorded and reported. Screening and full text assessment will be undertaken by two independent reviewers with any disagreement resolved through discussion. Where consensus cannot be reached this will be achieved through arbitration with a third reviewer. The results of the search will be reported in full in the final report and presented in a Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) flow diagram (14).
Data extraction:
Data will be extracted using an adaptation of a standardized data extraction tool which will be piloted prior to commencement of full data extraction. Extracted data will reflect the review question, reported as identified in the included studies to reduce the risk of introducing bias. It will include details of study population, setting, context, phenomena of interest, methodology and methods, multi-level factors associated with access and receipt of treatment and the primary outcome. Main findings will be extracted and assigned a level of credibility based upon methodological quality and risk of bias.
Assessment of methodological quality and risk of bias:
Methodological quality of included studies will be assessed using the Mixed Methods Appraisal Tool (MMAT). (15) This will be undertaken by two independent reviewers with any disagreement resolved through discussion or where required with arbitration from a third reviewer. This process will be followed for quantitative and qualitative studies. The results of critical appraisal will be reported in narrative form accompanied by a summary table. Risk of bias for included studies will be classified as low risk, high risk, or unclear (either lack of information or uncertainty over the potential for bias). The Cochrane Collaboration tool for assessing risk of bias will be used for included randomised controlled trials and the preliminary risk of bias in non-randomised studies - of exposures (ROBINS-E) tool will be used for non-randomised interventional studies. (16, 17). Studies will not be excluded based upon low methodological quality or credibility, however this will be reflected in the analysis and synthesis.
Data analysis, synthesis and integration:
The review will follow a segregated approach to analysis and synthesis. This will involve distinct quantitative and qualitative analysis and synthesis followed by integration of the resultant evidence. Analysis and synthesis of quantitative included studies will be presented in narrative form together with tables and figures to aid data presentation. The narrative will be structured around multi-level factors which have shown an association with access and receipt of treatment as the primary outcome measure for the review. This will be determined a priori guided by the theoretical model of access adopted to guide the review (10). Factors associated with access and receipt will be classified as individual, clinical and contextual. Where possible data will be pooled using statistical meta-analysis. This will be undertaken in accordance with guidance for meta-analysis of observational studies where appropriate. Heterogeneity will be assessed using the standard chi squared and I2 tests (18). Analyses will be performed using a random effects model to estimate a summary measure of access and treatment receipt for each factor, with an overall summary measure of the likelihood of receipt of treatment for each included study. Qualitative findings will be presented in narrative form using a narrative synthesis approach (19). Where possible these will be pooled using meta-aggregation to produce a comprehensive set of synthesized qualitative findings. Final synthesis of quantitative and qualitative findings will combine the separate synthesis into a set of conclusions which will reflect the narrative synthesis of qualitative findings and the quantitative findings produced from meta-analysis (where appropriate) to configure a mixed research synthesis.