Summary
Evaluation of the pilot implementation of unsupported and ICT-supported case finding of patients with ovarian cancer at risk of a genetic mutation in primary care suggests that both strategies are effective in identifying women with a history of epithelial ovarian cancer and referring them for GCT.
Implementation in almost 100 general practices resulted in referral of 10 patients with a history of epithelial ovarian cancer who were eligible for genetic counselling and DNA testing. Consequently, a BRCA2 gene mutation was found in one patient, leading to treatment of a not previously diagnosed early ovarian cancer in one of her family members. Patients and GPs generally considered both strategies desirable, mainly based on relevance and workability. According to GPs, technical barriers are the main obstacles to their success.
Strengths and limitations
This pilot study has several strengths. First, the pilot implementation of the case-finding strategies in daily practice provides a realistic rather than theoretical assessment of the effects and acceptance. Furthermore, the simultaneously executed strategies showed similar findings, particularly relating to acceptance, which supports the reliability of the findings.
However, several methodological and practical limitations should be kept in mind when considering these findings. To attain optimal certainty about the effect on case finding and referral, a randomised controlled design using an intervention and control arm would have been preferable. The research design may have led to an overestimation of the effect of the strategies, because it was assumed that all new referrals for GCT of eligible patients with a history of ovarian cancer were due to the intervention strategies. GPs may also have referred eligible patients without intervention, in line with the recent guideline recommending referral of women with a history of epithelial ovarian cancer. However, given the novelty of the guideline and GPs’ lack of familiarity with the guidelines of the Netherlands Comprehensive Cancer Organization (IKNL) in primary care, which are not part of the primary guidelines generally used by GPs, it may be assumed that potential overestimation of effectiveness would be minimal at most.
In contrast, the effect of the strategies may have been underestimated, mainly because of the limited possibilities of the research team to stimulate the response rate by GPs. Only identification, eligibility, approach, and referral reported by GPs to the research team were included in the analyses. If the GP acted on these strategies without reporting to the research team during or outside the follow-up period, these patients were not included in analyses. Corresponding underestimation of effect is also suggested by the observation that, out of the 48 patients who were approached for GP consultation and referral, for 16 patients the GP did not report on their acceptance or decline of the invitation and referral, whereas there were 16 registered acceptances of referral and 12 patients who declined.
The ovarian cancer screening method in strategy B, based on diagnostic codes in the EMR with subsequent reporting to GPs using pseudonymised patient identifiers, had not been used before. This led to technical barriers that hampered optimal execution of the ICT-supported strategy. This is likely to have counteracted the effectiveness and acceptance of this strategy. When implementing a new ICT supported system, similar barriers are likely to be experienced by GPs. Preventing or overcoming these problems will presumably enhance the future effectiveness and acceptance of this strategy. The encountered technical barriers might also explain the higher number of GPs returning the questionnaire in strategy B compared with strategy A.
A limitation of strategy B is the result of the limitations of registration systems that use diagnostic codes. This should be kept in mind when interpreting the results and when considering implementation in other healthcare systems using diagnostic codes in the EMR. It should also be considered that completeness and reliability of diagnostic codes may be affected by incomplete diagnostic codes (false negatives); misclassification as the diagnostic code used in this strategy (X77.02 — ovarian cancer) is a subcode of X77 — malignancy female genitals;17 and the inclusion of deceased patients and patients who have moved but remain in the EMR system.
These limitations in diagnostic codes also result in limited comparability of the number of ‘patients with ovarian cancer identified’ provided in Table 2, because the population represented by diagnostic codes in this denominator differs from the ‘ovarian cancer patients identified’ based on GPs’ knowledge in strategy A.
When comparing referral rates, it should also be considered that the check by the research team, whether patients had already been referred to the clinical geneticist, was only offered in strategy A.
A final limitation is that the modest questionnaire response rate may have resulted in selective responses concerning desirability and feasibility. Questionnaires may be more likely to be returned in case of particular concerns or approval concerning an intervention. This could lead to overestimation of positive and negative trends in responses. The higher questionnaire response rate in strategy B may be a reflection of the technical barriers experienced by GPs in strategy B.
Comparison with existing literature
Although the need for systematic efforts to identify patients with a history of epithelial ovarian cancer is widely supported in the literature, to the authors’ knowledge no studies addressing the effectiveness of case finding of these patients in primary care have been published previously.9–12 The aforementioned suggestion that the GP is in a suitable position to identify and refer women with a history of ovarian cancer and that GPs are willing to take that role is confirmed by the study’s findings.13–15,20
Information concerning cost-effectiveness is also valuable if implementation is considered. Recently, it has been shown that implementing secondary care germline BRCA testing in all patients newly diagnosed with ovarian cancer is extremely likely (99.9%) to be cost-effective.21 Given the low incremental cost-effectiveness ratio of this secondary care strategy (£4339 per quality-adjusted life year), and the low additional costs of the intervention (sending a letter and/or retrieval of diagnostic code) and minimal additional clinical burden (GP consultation), the intervention described in the current study seems likely to be cost-effective. However, it would be useful to include a cost-effectiveness analysis in a larger-scale randomised controlled trial or implementation study.
The literature has shown that the main barrier to integrating genetics in primary care is the perceived complexity of genetic risk exploration and the absence of clear and accessible guidelines.13–15 The fact that these barriers can easily be overcome by an intervention that provides the succinct and simple message to GPs to ‘refer all patients with a history of ovarian cancer’ explains the effectiveness and acceptance demonstrated by this study.
Implications for research and practice
An unsupported strategy and an ICT-supported strategy for case finding women with a history of ovarian cancer in primary care for genetic counselling and testing both show promising effectiveness and acceptance. Although these pilot results are promising, a large-scale implementation study is required to confirm and elaborate on the findings, for example, by including a cost-effectiveness analysis of the case-finding strategies.
By the standards for satisfactory effectiveness that were set before the pilot (over 25% active follow-up of intervention by GP and more than 50% of referred patients seen by clinical geneticist), the findings support primary care-based case finding of women with a history of ovarian cancer using either strategy. Nevertheless, acceptability of yield and preferred strategy are subject to preference and regional standards and setting. For any regional strategy, local opportunities and barriers should be recognised before designing and implementing an ovarian cancer case-finding strategy.