Configuration of services

Configuration of services

Ovarian cancer: identifying and managing familial and genetic risk

Evidence review C

NICE Guideline, No. 241

London: National Institute for Health and Care Excellence (NICE); 2024 Mar.

ISBN-13: 978-1-4731-5823-8

Configuration of services

Review question

What is the most effective configuration of services for referral, risk assessment and risk management for women at increased risk of ovarian cancer (including fertility, menopause and psychological support services)?

Introduction

Women with a familial risk of ovarian cancer are asked to manage a complex set of health needs. They need to understand their lifetime risk of ovarian cancer and decide upon interventions that can impact on their fertility, self-image, and menopause status. In addition, surgical interventions are not without their own set of risks. Services need to be established that can holistically support women with a familial risk of ovarian cancer through this process. However, the exact nature and composition and configuration is not fully known.

Herein we discuss the evidence base for these recommendations and outline how these services should be commissioned. Where there is a lack of evidence, we will also outline key research priorities.

Summary of the protocol

See Table 1 for a summary of the Population, Intervention, Comparison and Outcome (PICO) characteristics of this review.

Table 1

Summary of the protocol (PICO table).

For further details see the review protocol in appendix A.

Methods and process

This evidence review was developed using the methods and process described in Developing NICE guidelines: the manual. Methods specific to this review question are described in the review protocol in appendix A and the methods document (supplementary document 1).

Declarations of interest were recorded according to NICE’s conflicts of interest policy.

Effectiveness/ Service delivery evidence

Included studies

Eleven observational studies were included for this review. They compared a variety of service delivery models mainly against a standard service delivery, and mainly in women with ovarian cancer.

Three studies compared a mainstreaming cancer genetic testing/counselling/service with no mainstreaming cancer genetic service in women with ovarian cancer (Ip 2020, Yoon 2022) and in women with breast cancer (Scott 2020).

One study compared a streamlined pre-test genetic education and genetic testing service with a standard service delivery in women with ovarian cancer (Powell 2020).

Two studies compared a gynaecologic oncologist-initiated genetic testing service with a standard genetic testing service (Piedimonte 2020, Rumford 2020).

Three studies compared a model with the addition of an embedded genetic counsellor in the medical and/or gynaecologic oncology clinic with a standard service delivery (Rana 2021, Senter 2017, Warias 2021).

One study compared a reflex BRCA1/2 tumour testing with a no reflex BRCA1/2 tumour testing in women with ovarian cancer (McCuaig 2020).

One study compared a multidisciplinary one-stop follow-up clinic with a no multidisciplinary one-stop follow-up clinic in BRCA1/2 carriers (Pichert 2010).

The included studies are summarised in Table 2.

See the literature search strategy in appendix B and study selection flow chart in appendix C.

Excluded studies

Studies not included in this review are listed, and reasons for their exclusion are provided in appendix K.

Summary of included studies

Summaries of the studies that were included in this review are presented in Table 2.

Table 2

Summary of included studies.

See the full evidence tables in appendix D. No meta-analysis was conducted (and so there are no forest plots in appendix E).

Summary of the evidence

Studies reported a variety of different configuration services for referral, risk assessment and management, therefore it is difficult to draw an overall conclusion. Effect estimates could not be calculated for all studies as not all of them reported relevant data, therefore some of the results reported here are based on the significance or non-significance of the findings reported in the studies.

Women with ovarian cancer

Mainstream germline genetic testing program versus cancer genetic service

Low quality evidence comparing mainstream genetic testing to the cancer genetic service was inconclusive in terms of time from blood collection to report/return to the treating oncologist. Although it was not reported whether there was a statistical difference between the mainstream genetic testing and the standard genetic service, it was reported that the average time from blood collection to report was 7 days longer with the mainstream genetic testing program than with the cancer genetic service.

Mainstreaming genetic counselling versus standard genetics referral pathway

Very low to moderate quality evidence indicated no important difference in terms of either psychosocial aspects within the cancer genetic counselling setting (a proxy for quality of life) or with the genetic counselling satisfaction among women participating in the mainstreaming genetic counselling as compared to the standard cancer referral pathway.

Streamlined pre-test genetic education and genetic panel testing versus standard counselling and testing

One study did not report whether time from diagnosis to genetic test result or to blood draw was significantly different between a streamlined pre-test genetic education and genetic panel testing service delivery model (where testing is provided by the managing gynaecologic oncologists) and the standard counselling and testing. However, it reported that the time from diagnosis to genetic test result (median 12 days shorter) and also to blood draw (median 7 days shorter) was shorter with the streamlined pre-test genetic education and genetic testing panel testing service as compared to the current counselling and testing.

Very low to low quality evidence showed no important difference in terms of patient satisfaction associated with the genetic testing, including, for example, uncertainty, positive experience, satisfaction with time for discussion and adequacy of information provided and others when compared the streamlined pre-test genetic education and genetic panel testing with the current counselling and testing. In terms of distress associated with genetic testing, there was no evidence of an important difference between the two services (low quality evidence).

Gynaecologic oncologist-initiated genetic testing model versus traditional genetics referral

Very low quality evidence showed a shorter time from diagnosis to genetic testing (median 114 days shorter) and a shorter delay between the testing and the result (median 20.5 days shorter) with the gynaecologic oncologist-initiated genetic testing model as compared to the traditional care model It is not clear whether there was a significant difference between the two models in terms of the above outcomes as it was not reported in the study.

In terms of time between blood sample acquisition and return of the result to the treating oncologist, it is not clear whether there was any significant difference between the two models as it was not reported. However, it was reported that the turnaround time was shorter (mean 127.6 days shorter) with the gynaecologic oncologist-initiated genetic testing model.

Embedded genetic counsellor in the medical and gynaecologic oncology clinic versus standard clinic

Low quality evidence showed a shorter time from initial consultation to genetic counselling or from referral to scheduling in genetics, and to completion of genetics consultation with an embedded genetic counsellor in the medical/gynaecologic oncology clinic or with a cancer genetic counsellor on-site in the gynaecologic oncology clinic as compared to standard care models. In terms of the proportion of patients seen for ovarian cancer treatment who received genetic testing within 3 months of their initial visit (a proxy for the time to treatment outcome), moderate quality evidence showed an important benefit of the service with an embedded genetic counsellor as compared to the standard service.

Genetics embedded model versus no genetic embedded model

One study reported a shorter time from referral to scheduling in genetics (mean 3.13 months) and to completion of genetics consultation (mean 0.85 months) with the genetics embedded model as compared to no genetics embedded model (moderate quality evidence).

Collaborative care model versus no collaborative care model

In terms of time from diagnosis to referral and also to first appointment, one study reported a shorter time with the collaborative care model involving the integration of genetic counsellors into tumour board round as compared to no collaborative care model (low quality evidence).

Reflex BRCA1/2 testing versus no reflex testing

Very low quality evidence from 1 study assessing the reflex BRCA1/2 tumour testing (where genetic testing of tumour tissue is initiated by a pathologist as part of surgical pathology review) reported a shorter time to referral for genetic counselling (median 26 days shorter) with the reflex tumour testing model as compared to the no reflex tumour testing model.

Women with breast cancer

Nurse-led mainstreaming cancer genetics (MCG) service verses pre-MCG service

Very low quality evidence from 1 study assessing a specialist, nurse-led mainstreaming cancer genetics service in women with a positive breast cancer diagnosis having a genetic test was inconclusive as it did not report whether there was a statistical difference between the specialist, nurse-led mainstreaming cancer genetic service and the usual service in terms of time from genetic testing to the test result.

BRCA1/2 carriers

Multidisciplinary one-stop follow-up clinic verses no one-stop clinic

In terms of the recruitment to trials, moderate quality evidence showed an important benefit of the multidisciplinary clinic as compared to no multidisciplinary clinic.

See appendix F for full GRADE tables.

Economic evidence

Included studies

A systematic review of the economic literature was conducted but no economic studies were identified which were applicable to this review question.

A single economic search was undertaken for all topics included in the scope of this guideline. See supplementary material 2 for details.

Excluded studies

Economic studies not included in this review are listed, and reasons for their exclusion are provided in appendix J.

Summary of included economic evidence

No economic studies were identified which were applicable to this review question.

Economic model

No economic modelling was undertaken for this review because the committee agreed that other topics were higher priorities for economic evaluation.

Evidence statements

Economic

No economic studies were identified which were applicable to this review question.

The committee’s discussion and interpretation of the evidence

The outcomes that matter most

Overall survival and quality of life were prioritised as critical outcomes by the committee because they indicate the impact of services on the long-term health and wellbeing of those at increased risk of ovarian cancer. Patient satisfaction was also a critical outcome as a way of comparing the relative acceptability of different service configurations.

Access to services was chosen an important outcome to capture the efficiency and convenience of different service models. Examples of access were local availability, waiting times for services, time to diagnosis or identification of a familial risk, time to treatment (risk reducing), and access to clinical trials.

The quality of the evidence

The quality of the evidence from the included studies was assessed with GRADE and was rated as mainly very low or low mainly due to serious risk of bias of individual studies and in some cases also due to imprecision of the estimate. Serious risk of bias was typically due to incomplete adjustment for confounders, so baseline differences between people seen in different service configurations could bias the results.

There was no evidence identified for overall survival and local availability. This meant that the committee used their experience and expertise to estimate the longer term impact of different service configurations.

Benefits and harms

The committee noted that the variety of configurations of services reported in the evidence made it difficult to identify a single ideal service configuration, but they noted that certain features such as embedded specialisms within the team, mainstreaming of genetic counselling and teams that collaborated were associated with important benefits, that is better outcomes such as shorter waiting times for referral, and subsequently to genetic counselling and testing. The relatively small number of studies and uncertainties about the reported effects and the way the studies were conducted meant the recommendations were largely based on their knowledge and experience.

Commissioners and services providers in all settings

The committee explained that there are well-established referral mechanisms and pathways to clinical genetics. However, there is variation in the referral criteria, the minimum dataset accepted prior to referral, and also among clinicians in primary and secondary care regarding whether and how to make a referral. Therefore, the committee aimed to provide guidance that should help reduce this variation in practice.

They agreed, based on their experience, that commissioners and service providers should ensure that there are referral pathways from primary or secondary care for people at risk of having a pathogenic variant associated with ovarian cancer could be facilitated by clear referral criteria, an online referral form for referral, family history questionnaire filled out by the affected person, and standardised patient information leaflets (for example, a web page or paper form). For example, currently some genetic specialist services do not accept patients without a detailed family history, including a family history questionnaire streamlines the referral process. The committee also agreed that laying out specific referral criteria would help the referring clinician and standardise the process.

The committee acknowledged that healthcare professionals and the general public are not sufficiently aware of which groups may be at risk which may lead to people not coming forward who would be eligible for testing. They therefore recommended that awareness raising should also be under the remit of commissioners and service providers. They discussed various public awareness initiatives for other conditions that may also be applicable for ovarian cancer (such as those related to familial breast cancer) and also noted that it could feature in continuing education of healthcare professionals. The agreed that this may improve early identification of those at risk.

The committee discussed, based on their experience, that some people such as those with physical, cognitive or sensory disabilities, some diverse ethnic groups as well as men, trans people and non-binary people may be under referred to genetic services. They agreed to recommend that commissioners and service providers should be responsible for equality and inclusiveness training, and information provision for healthcare professionals in primary and secondary care to address this.

Primary care services

The committee agreed that primary care healthcare professionals have no capacity to seek out potential index cases, however, in cases where for example a family history is known or where they are from an at-risk population they can make a referral to genetic services (see also the discussion on other referral criteria in evidence review D). Based on their experience, the committee listed the main responsibilities of primary care healthcare professionals such as providing information and support and referral to genetic services and/or other specialist services.

Genetic services

The committee agreed to list the main responsibilities of genetic services including providing information and support, pathogenic variant risk assessment, genetic counselling and testing, cascade testing of relatives, discussion of potential management options and referral to the familial ovarian cancer multidisciplinary team, so people know what to expect when referred. This would mainly include genetic counselling and genetic testing of people at risk of having a pathogenic variant without a personal history of epithelial ovarian cancer. However, the committee specified that it should be within the remit of genetic services to provide genetic counselling and genetic testing to those diagnosed with rare non-epithelial ovarian cancers (ovarian Sertoli–Leydig cell tumour, small cell carcinoma of the ovary hypercalcaemic type, ovarian sex cord tumour with annular tubules, embryonal rhabdomyosarcoma of the ovary or ovarian gynandroblastoma) – for the discussion of the list of cancers see evidence review I.

Gynaecology oncology multidisciplinary team

Based on the evidence which showed some important benefits of genetic testing and counselling where the gynaecology oncology team takes responsibility, the committee agreed that mainstream genetic counselling and testing of women with a histopathological diagnosis of epithelial ovarian cancer should be carried out by their gynaecology oncology multidisciplinary team. They agreed that in general the evidence indicated that counselling provided within the gynaecology oncology multidisciplinary team would be more efficient and faster for women with ovarian cancer to access than referral to genetics services.

Familial ovarian cancer multidisciplinary team

The committee discussed the management of people who carry a pathogenic variant and those who are above a risk threshold. The committee acknowledged the significant variation in practice in the way risk is managed for this population. To standardise practice and provide coordinated lifelong care for people at risk of familial ovarian cancer the committee agreed to list the responsibilities of the MDT and also a familial ovarian cancer multidisciplinary team approach consisting of members with expertise in clinical genetics, gynaecology and gynaecological oncology would be the most appropriate. This was also partly based on the evidence about the multidisciplinary management of people who are carriers of pathogenic variants, which showed better recruitment to clinical trials with a multidisciplinary one-stop follow-up clinic.

The committee agreed patients would require access to a range of different services during their lifetime which they do not currently always have direct access to. Psychology services may be needed if the person is distressed or is finding it impossible to reach a decision; fertility or menopause services would be needed when risk reducing surgery is being considered; breast and ovarian cancer services could be needed if cancer is suspected and colorectal services may be needed for people with Lynch syndrome They gave these as examples but did not rule out that others may be needed on a case by case basis. They therefore decided to recommend that there are agreed referral pathways to such specialist services through the familial ovarian cancer multidisciplinary team.

Cost effectiveness and resource use

There was no existing economic evidence identified for this review.

The committee noted the existence of variation in the referral criteria, the minimum dataset accepted prior to referral, and also practices among clinicians in primary and secondary care regarding whether and how to make a referral. Therefore, the recommendation in this area should help reduce such variation in practice. There was some discussion about family history questionnaires and it was noted that patients are generally responsible for their completion. It was agreed that an online referral form to specialist services could be completed within minutes, for example by GPs.

This recommendation may also result in an increased number of people accessing genetic services, potentially creating additional pressure on existing services. However, the committee explained that the costs associated with genetic testing and counselling are low compared with the potential benefits. Identifying people with pathogenic variants could significantly reduce their risk of cancer and associated costs.

There are various training programmes on equality and inclusiveness issues available for NHS staff. The recommendation for this will not require services to set up new training, create new information resources nor is it expected to require additional resources to implement.

The committee discussed primary care and genetic services’ responsibilities for people at risk of familial ovarian cancer. This recommendation represents current practice and will not require additional resources to implement. Similarly, the committee explained that people diagnosed with epithelial ovarian cancer would be under the care of gynaecology oncology multidisciplinary team who would be initiating genetic counselling and testing which is current practice across services. Reducing these variations will also help to ensure that people have equal access to genetic testing.

The committee discussed familial ovarian cancer multidisciplinary teams’ composition, roles and responsibilities. These teams may not exist in every cancer centre and recommendations on this may represent a change in practice for some services. Most cancer services are expected to have access to psychological services, menopause services etc. This recommendation is about ensuring that multidisciplinary teams have links to existing specialist services and do not require establishment of new services.

The committee noted that support services should have the capacity to meet the referrals from ovarian cancer services. However, the committee highlighted that some services have staff shortages, which may impact the implementation of this recommendation. It was also acknowledged that due to the more streamlined organisation of services for people with familial ovarian cancer, more people might access support services earlier, potentially creating additional pressure on the services. Nevertheless, the committee agreed that under resourcing of services should not prevent them making recommendations on access to such services.

There was further discussion about how these multidisciplinary teams are set up. They explained that while access to specialists is essential and the overall care is coordinated by them, physical co-location of these specialists in a single clinic is not required. The committee was of a view that setting up familial ovarian cancer multidisciplinary teams, in cases where they are currently lacking, is unlikely to require significant resources. They noted that any additional costs associated with setting up these teams would be outweighed by the benefits they offer, including coordinated and timely access to appropriate care, such as risk-reducing surgery. These teams can effectively reduce individuals’ cancer risk and associated care costs.

Other factors the committee took into account

The committee discussed that there were some configuration of service models which were not included in this review because they were not comparative. They mentioned the mainstream genetic testing pathway in which testing was undertaken by the trained cancer team with cascade testing to relatives performed by the genetics team (George et al. 2016). This testing pathway showed that the mainstream BRCA testing required fewer appointments, fewer referrals to genetics teams and was quicker overall. However, this study did not impact the recommendations.

Recommendations supported by this evidence review

This evidence review supports recommendations 1.1.1 to 1.1.9 in the NICE guideline.

References – included studies

Effectiveness

Ip 2022
Ip, E., Young, A.L., Scheinberg, T. et al. (2022) Evaluation of a mainstream genetic testing program for women with ovarian or breast cancer. Asia-Pacific Journal of Clinical Oncology First published: 30 January 2022 [PubMed: 35098668]
McCuaig 2020
McCuaig, Jeanna M, Care, Melanie, Ferguson, Sarah E et al. (2020) Year 1: Experiences of a tertiary cancer centre following implementation of reflex BRCA1 and BRCA2 tumor testing for all high-grade serous ovarian cancers in a universal healthcare system. Gynecologic oncolog 158(3): 747–753 [PubMed: 32674931]
Pichert 2010
Pichert, G, Jacobs, C, Jacobs, I et al. (2010) Novel one-stop multidisciplinary follow-up clinic significantly improves cancer risk management in BRCA1/2 carriers. Familial cance 9(3): 313–9 [PubMed: 20300867]
Piedimonte 2020
Piedimonte, Sabrina, Power, Joanne, Foulkes, William D et al. (2020) BRCA testing in women with high-grade serous ovarian cancer: gynecologic oncologist-initiated testing compared with genetics referral. International journal of gynecological cancer: official journal of the International Gynecological Cancer Societ 30(11): 1757–1761 [PubMed: 32759180]
Powell 2020
Powell, C Bethan, Laurent, Cecile, Ciaravino, Giuseppe et al. (2020) Streamlining genetic testing for women with ovarian cancer in a Northern California health care system. Gynecologic oncolog 159(1): 221–228 [PubMed: 32778409]
Rana 2021
Rana, Huma Q, Kipnis, Lindsay, Hehir, Kristin et al. (2021) Embedding a genetic counselor into oncology clinics improves testing rates and timeliness for women with ovarian cancer. Gynecologic oncolog 160(2): 457–463 [PubMed: 33229043]
Rumford 2020
Rumford, M., Lythgoe, M., McNeish, I. et al. (2020) Oncologist-led BRCA ‘mainstreaming’ in the ovarian cancer clinic: A study of 255 patients and its impact on their management. Scientific Report 10(1): 3390 [PMC free article: PMC7042365] [PubMed: 32098980]
Scott 2020
Scott N, O’Sullivan J, Asgeirsson K et al. (2020) Changing practice: moving to a specialist nurse-led service for BRCA gene testing. British journal of nursing (Mark Allen Publishing 29(10): S6–S13 [PubMed: 32463748]
Senter 2017
Senter, Leigha, O’Malley, David M, Backes, Floor J et al. (2017) Genetic consultation embedded in a gynecologic oncology clinic improves compliance with guideline-based care. Gynecologic oncolog 147(1): 110–114 [PubMed: 28800943]
Warias 2021
Warias, Ashley, Ferguson, Meghan, Chamberlain, Erin et al. (2021) Universal access to genetic counseling for women with epithelial ovarian cancer in Nova Scotia: Evaluating a new collaborative care model. Journal of genetic counselin 30(5): 1491–1499 [PubMed: 33876505]
Yoon 2022
Yoon, Sook-Yee, Wong, Siu Wan, Lim, Joanna et al. (2022) Oncologist-led BRCA counselling improves access to cancer genetic testing in middle-income Asian country, with no significant impact on psychosocial outcomes. Journal of medical genetic 59(3): 220–229 [PubMed: 33526602]

References - other

George, A, Riddell, D, Seal, S et al. (2016) Implementing rapid, robust, cost-effective, patient-centred, routine genetic testing in ovarian cancer patients. Scientific Report 13(6): 29506 [PMC free article: PMC4942815] [PubMed: 27406733]

Appendices

Appendix E. Forest plots

Forest plots for review question: What is the most effective configuration of services for referral, risk assessment and risk management for women at increased risk of ovarian cancer (including fertility, menopause and psychological support services)?

No meta-analysis was conducted for this review question and so there are no forest plots.

Appendix F. GRADE tables

GRADE tables for review question: What is the most effective configuration of services for referral, risk assessment and risk management for women at increased risk of ovarian cancer (including fertility, menopause and psychological support services)? (PDF, 323K)

Appendix G. Economic evidence study selection

Study selection for: What is the most effective configuration of services for referral, risk assessment and risk management for women at increased risk of ovarian cancer (including fertility, menopause and psychological support services)?

One global search was undertaken – please see Supplement 2 for details on study selection.

Appendix H. Economic evidence tables

Economic evidence tables for review question: What is the most effective configuration of services for referral, risk assessment and risk management for women at increased risk of ovarian cancer (including fertility, menopause and psychological support services)?

No evidence was identified which was applicable to this review question.

Appendix I. Economic model

Economic model for review question: What is the most effective configuration of services for referral, risk assessment and risk management for women at increased risk of ovarian cancer (including fertility, menopause and psychological support services)?

No economic analysis was conducted for this review question.

Appendix J. Excluded studies

Excluded studies for review question: What is the most effective configuration of services for referral, risk assessment and risk management for women at increased risk of ovarian cancer (including fertility, menopause and psychological support services)?

Excluded effectiveness/ service delivery studies

Table 14

Excluded studies and reasons for their exclusion.

Excluded economic studies

No economic evidence was identified for this review. See supplementary material 2 for further information.

Appendix K. Research recommendations – full details

Research recommendations for review question: What is the most effective configuration of services for referral, risk assessment and risk management for women at increased risk of ovarian cancer (including fertility, menopause and psychological support services)?

No research recommendations were made for this review question.

Final

Evidence reviews underpinning recommendations 1.1.1 to 1.1.9 in the NICE guideline

These evidence reviews were developed by NICE

Disclaimer: The recommendations in this guideline represent the view of NICE, arrived at after careful consideration of the evidence available. When exercising their judgement, professionals are expected to take this guideline fully into account, alongside the individual needs, preferences and values of their patients or service users. The recommendations in this guideline are not mandatory and the guideline does not override the responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or their carer or guardian.

Local commissioners and/or providers have a responsibility to enable the guideline to be applied when individual health professionals and their patients or service users wish to use it. They should do so in the context of local and national priorities for funding and developing services, and in light of their duties to have due regard to the need to eliminate unlawful discrimination, to advance equality of opportunity and to reduce health inequalities. Nothing in this guideline should be interpreted in a way that would be inconsistent with compliance with those duties.

NICE guidelines cover health and care in England. Decisions on how they apply in other UK countries are made by ministers in the Welsh Government, Scottish Government, and Northern Ireland Executive. All NICE guidance is subject to regular review and may be updated or withdrawn.

Bookshelf ID: NBK604387PMID: 38896762

Table 2Summary of included studies

Study	Population	Intervention^*	Comparison^*	Outcomes
Ip 2022 Retrospective cohort Australia	N=289 women with ovarian cancer Age, median (range), years: 60 (34-93)	Mainstream germline genetic testing program	Cancer genetic service	Time to diagnosis or identification of a familial risk Time from blood collection to report
McCuaig 2020 Retrospective cohort Canada	N=212 (analysed n=175) women with newly diagnosed high-grade serous ovarian cancer (including cases of primary peritoneal or fallopian tube cancers) Age, median (range), years: 63.8 (38.1-90)	Reflex BRCA1/2 tumour testing	No Reflex BRCA1/2 tumour testing	Time to diagnosis or identification of a familial risk Time to referral for genetic counselling
Pichert 2010 Retrospective cohort UK	N=172 BRCA1/2 carriers who choose to attend the MDOSC Age, years: out of 164 women <20=1%, 21-30=9%, 31-40=27%, 41-50=29%, 51-60=20%, 61-70=13%, >71=1%	Multidisciplinary one-stop follow-up clinic (MDOSC)	No MDOSC	Access to clinical trials Recruitment to trials
Piedimonte 2020 Retrospective case series Canada	N=152 patients diagnosed with high-grade serous ovarian, tubal, or peritoneal cancer Age: not reported	Gynaecologic oncologist-initiated genetic testing model	Traditional genetics referral-based program	Time to diagnosis or identification of a familial risk Time from diagnosis to genetic testing Delay between testing and result
Powell 2020 Prospective cohort USA	N=141 women with newly diagnosed epithelial ovarian, fallopian tube and peritoneal cancer Age, median, years: streamlining group 63.5; standard testing group 65	Streamlined pre-test genetic education and genetic panel testing	Current standard process of referral for genetic counselling and testing	Time to diagnosis or identification of a familial risk Time from diagnosis to genetic test result Time from diagnosis to notification of test result Patient satisfaction
Rana 2021 Prospective cohort USA	N=254 women ovarian, fallopian, or primary peritoneal carcinomas Age, n, years: in the intervention group 50-59=36 (30.3%), 60-69=37 (31.1%); in comparison group 50-59=39 (28.9%), 60-69=44 (32.6%)	Addition of an embedded genetic counsellor in the medical and gynaecologic oncology clinic	Standard medical and gynaecologic oncology clinic	Time to diagnosis or identification of a familial risk Time to genetic counselling Time to treatment (risk reducing) Proportion of patients seen for ovarian cancer treatment who received genetic testing within 3 months of their initial visit
Rumford 2020 Retrospective cohort UK	N=255 ovarian cancer patients, previously untested for germline BRCA mutations, but n=199 samples used for the outcome of the mean time between blood sample acquisition and return of BRCA result to the treating oncologist (not clear how many in each group) Age, mean (range), years: 62.2 (31-91)	Oncologist-led BRCA testing mainstreaming service	Standard BRCA testing service before the implementation of mainstreaming service	Time to diagnosis or identification of a familial risk Time between blood sample acquisition and return of BRCA result
Scott 2020 Retrospective cohort UK	Women who were having a diagnostic genetic test because they had a positive breast cancer diagnosis. Specialist, nurse-led mainstreaming cancer genetics service n=290, Pre-MCG service = not reported, data based on average service data Age, mean (range), years (reported for those in the intervention group only): 2016 = 47.44 (23-70), 2017 = 49.81 (29-70), 2018 = 48.9 (24-80)	Specialist, nurse-led mainstreaming cancer genetics service (MCG)	Pre-MCG service	Time to diagnosis or identification of a familial risk Time from testing until genetic test result
Senter 2017 Retrospective cohort USA	N=737 patients with newly diagnosed ovarian cancer Age: not reported	Genetics embedded model (GEM; incorporates a cancer genetic counsellor on-site in the gynaecologic oncology clinic)	No genetics-embedded model of service (cancer genetics services provided as an off-site consultation)	Time to diagnosis or identification of a familial risk Time from referral to scheduling in genetics Time from referral to completion of genetics consultation
Warias 2021 Retrospective cohort Canada	N=386 women with a new pathologic diagnosis of epithelial ovarian cancer Age (n), years: in the intervention group: =>60 = 29 (34%), <60=56 (66%); in the comparison group: =>60 = 214 (71%), <60=87 (29%)	Collaborative care model involving the integration of genetic counsellors into tumour board round	No collaborative care model	Time to diagnosis or identification of a familial risk Time from diagnosis to referral Time from referral to first appointment
Yoon 2022 Prospective cohort Malaysia	N=790 but analysed n=512 women with newly diagnosed with non-mucinous ovarian, fallopian tube or primary peritoneal cancer Age, mean (SD), years: 52.4 (10.8)	Mainstreaming genetic counselling	Standard genetics referral pathway	Quality of life Psychosocial impact Patient satisfaction Satisfaction with genetic counselling

: GEM: genetics embedded model; MCG: mainstreaming cancer genetics; MDOSC: multidisciplinary one-stop follow-up clinic; SD: standard deviation

*: for details see Appendix D: Evidence tables

Table 14Excluded studies and reasons for their exclusion

Study	Reason for exclusion
Antill, Y.C.; Shanahan, M.; Phillips, K.-A. (2005) The integrated, multidisciplinary clinic: A new model for the ongoing management of women at high genetic risk for breast and ovarian cancer. Cancer Foru 29(2): 107–110	Comparator in study does not match that specified in this review protocol
Azzollini, J., Vingiani, A., Agnelli, L. et al. (2022) Management of BRCA Tumour Testing in an Integrated Molecular Tumour Board Multidisciplinary Model. Frontiers in Oncolog 12: 857515 [PMC free article: PMC9026437] [PubMed: 35463374]	Outcomes in study do not match those specified in this review protocol
Dhivya, Chandrasekaran, Monika, Sobocan, Oleg, Blyuss et al. (2021) Implementation of Multigene Germline and Parallel Somatic Genetic Testing in Epithelial Ovarian Cancer: SIGNPOST Study. Cancers (Basel) Aug 27;13(17):4344 [PMC free article: PMC8431198] [PubMed: 34503154]	Comparator in study does not match that specified in this review protocol
Colombo, Nicoletta, Huang, Gloria, Scambia, Giovanni et al. (2018) Evaluation of a Streamlined Oncologist-Led BRCA Mutation Testing and Counseling Model for Patients With Ovarian Cancer. Journal of clinical oncology: official journal of the American Society of Clinical Oncolog 36(13): 1300–1307 [PMC free article: PMC6804908] [PubMed: 29558274]	Comparator in study does not match that specified in this review protocol
D’Andrea, Elvira, Marzuillo, Carolina, De Vito, Corrado et al. (2016) Which BRCA genetic testing programs are ready for implementation in health care? A systematic review of economic evaluations. Genetics in medicine: official journal of the American College of Medical Genetic 18(12): 1171–1180 [PMC free article: PMC5159446] [PubMed: 27906166]	Intervention in study does not match that specified in this review protocol
DeFrancesco, M.S., Waldman, R.N., Pearlstone, M.M. et al. (2018) Hereditary cancer risk assessment and genetic testing in the community-practice setting. Obstetrics and Gynecolog 132(5): 1121–1129 [PubMed: 30303907]	Comparator in study does not match that specified in this review protocol
Drescher, Charles W, Beatty, J David, Resta, Robert et al. (2016) The effect of referral for genetic counseling on genetic testing and surgical prevention in women at high risk for ovarian cancer: Results from a randomized controlled trial. Cance 122(22): 3509–3518 [PMC free article: PMC5253334] [PubMed: 27447168]	Comparator in study does not match that specified in this review protocol
Evans, D Gareth, Astley, Susan, Stavrinos, Paula et al. (2016) Improvement in risk prediction, early detection and prevention of breast cancer in the NHS Breast Screening Programme and family history clinics: a dual cohort study [PubMed: 27559559]	Intervention in study does not match that specified in this review protocol
Firth, Clare, Jacobs, Christine, Evison, Margaret et al. (2011) Novel one-stop multidisciplinary follow-up clinic for BRCA1/2 carriers: patient satisfaction and decision making. Psychooncolog 20(12): 1301–1308 [PubMed: 22114045]	Comparator in study does not match that specified in this review protocol
Flaum N, Morgan RD, Burghel GJ et al. (2020) Mainstreaming germline BRCA1/2 testing in non-mucinous epithelial ovarian cancer in the North West of England. European journal of human genetics: EJHG vol. 28 (no. 11) [PMC free article: PMC7575602] [PubMed: 32651552]	Outcomes in study do not match those specified in this review protocol
Frey, Melissa K, Lee, Sarah S, Gerber, Deanna et al. (2020) Facilitated referral pathway for genetic testing at the time of ovarian cancer diagnosis: uptake of genetic counseling and testing and impact on patient-reported stress, anxiety and depression. Gynecologic oncolog 157(1): 280–286 [PubMed: 32057464]	Comparator in study does not match that specified in this review protocol
George, Angela, Riddell, Daniel, Seal, Sheila et al. (2016) Implementing rapid, robust, cost-effective, patient-centred, routine genetic testing in ovarian cancer patients. Scientific report 6: 29506 [PMC free article: PMC4942815] [PubMed: 27406733]	Comparator in study does not match that specified in this review protocol
Helsper, Charles W, Van Vliet, Liesbeth M, Velthuizen, Mary E et al. (2018) Identifying patients with a history of ovarian cancer for referral for genetic counselling: non-randomised comparison of two case-finding strategies in primary care. The British journal of general practice: the journal of the Royal College of General Practitioner 68(676): e750–e756 [PMC free article: PMC6193781] [PubMed: 30348886]	Outcomes in study do not match those specified in this review protocol
Interrante, Mary K, Segal, Hannah, Peshkin, Beth N et al. (2017) Randomized Noninferiority Trial of Telephone vs In-Person Genetic Counseling for Hereditary Breast and Ovarian Cancer: A 12-Month Follow-Up. JNCI cancer spectru 1(1): pkx002 [PMC free article: PMC6611491] [PubMed: 31304457]	Intervention in study does not match that specified in this review protocol
Kentwell, Maira, Dow, Eryn, Antill, Yoland et al. (2017) Mainstreaming cancer genetics: A model integrating germline BRCA testing into routine ovarian cancer clinics. Gynecologic oncolog 145(1): 130–136 [PubMed: 28162234]	Comparator in study does not match that specified in this review protocol
Lin, Jenny, Sharaf, Ravi N, Saganty, Rachel et al. (2021) Achieving universal genetic assessment for women with ovarian cancer: Are we there yet? A systematic review and meta-analysis. Gynecologic oncolog 162(2): 506–516 [PMC free article: PMC8424684] [PubMed: 34023131]	Systematic review used as source of primary studies
Moya-Alarcon, Carlota, Gonzalez-Dominguez, Almudena, Simon, Susana et al. (2019) Cost-utility analysis of germline BRCA1/2 testing in women with high-grade epithelial ovarian cancer in Spain. Clinical & translational oncology: official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexic 21(8): 1076–1084 [PubMed: 30617925]	Comparator in study does not match that specified in this review protocol
Petelin, Lara, Trainer, Alison H, Mitchell, Gillian et al. (2018) Cost-effectiveness and comparative effectiveness of cancer risk management strategies in BRCA1/2 mutation carriers: a systematic review. Genetics in medicine: official journal of the American College of Medical Genetic 20(10): 1145–1156 [PubMed: 29323669]	Intervention in study does not match that specified in this review protocol
Petzel, Sue V, Vogel, Rachel Isaksson, Bensend, Tracy et al. (2013) Genetic risk assessment for women with epithelial ovarian cancer: referral patterns and outcomes in a university gynecologic oncology clinic. Journal of genetic counselin 22(5): 662–73 [PMC free article: PMC4589274] [PubMed: 23677535]	Intervention in study does not match that specified in this review protocol
Powell, C Bethan, Littell, Ramey, Hoodfar, Elizabeth et al. (2013) Does the diagnosis of breast or ovarian cancer trigger referral to genetic counseling?. International journal of gynecological cancer: official journal of the International Gynecological Cancer Societ 23(3): 431–6 [PubMed: 23354368]	Comparator in study does not match that specified in this review protocol
Rahman, Belinda, Lanceley, Anne, Kristeleit, Rebecca S et al. (2019) Mainstreamed genetic testing for women with ovarian cancer: first-year experience. Journal of medical genetic 56(3): 195–198 [PubMed: 29535157]	Comparator in study does not match that specified in this review protocol
Ricci, Maria Teresa, Sciallero, Stefania, Mammoliti, Serafina et al. (2015) Referral of Ovarian Cancer Patients for Genetic Counselling by Oncologists: Need for Improvement. Public health genomic 18(4): 225–32 [PubMed: 26111740]	Comparator in study does not match that specified in this review protocol
Ricker, C., Lagos, V., Feldman, N. et al. (2006) If we build it… will they come? - Establishing a cancer genetics services clinic for an underserved predominantly latina cohort. Journal of Genetic Counselin 15(6): 505–514 [PubMed: 17106633]	Intervention in study does not match that specified in this review protocol
Smallwood, K G, Crockett, S, Huang, V et al. (2022) Changing patterns of referral into a family history clinic and detection of ovarian cancer: a retrospective 10-year review. Journal of obstetrics and gynaecology: the journal of the Institute of Obstetrics and Gynaecology: 1–7 [PubMed: 35980980]	Intervention in study does not match that specified in this review protocol
Swanson, Casey L, Kumar, Amanika, Maharaj, Joy M et al. (2018) Increasing genetic counseling referral rates through bundled interventions after ovarian cancer diagnosis. Gynecologic oncolog 149(1): 121–126 [PubMed: 29402500]	Outcomes in study do not match those specified in this review protocol
Wood, N J, Munot, S, Sheridan, E et al. (2008) Does a “one-stop” gynecology screening clinic for women in hereditary nonpolyposis colorectal cancer families have an impact on their psychological morbidity and perception of health? International journal of gynecological cancer: official journal of the International Gynecological Cancer Societ 18(2): 279–84 [PubMed: 17587321]	Intervention in study does not match that specified in this review protocol

Population	Women with familial ovarian cancer or at likely increased risk of familial ovarian cancer
Intervention	Any service delivery models (approaches, configurations of resources and services) for referral, risk assessment and risk management for women at increased risk of ovarian cancer. For example: Delivery arrangements: How, when and where assessments are done, for example: referral from primary care direct to consumer tests Who does assessments: mainstreaming of genetic testing for affected women (within oncology clinic vs. traditional genetic counselling model within clinical genetics) pathology reporting (for example, double reporting) Coordination of care and management of care processes, for example: one stop clinics (multiple specialties within the same clinic, for example, BRCA carrier clinics) multidisciplinary teams/working access to psychological, menopause and fertility services combined surgical procedures (for example, risk reducing mastectomy, risk reducing salpingo-oophorectomy) coordination of assessments amongst different providers
Comparison	Interventions compared with: Each other Combinations of interventions
Outcomes	Critical Overall survival Quality of life Patient satisfaction Important Access to services: Local availability (for example, time/distance travelled to access services) Waiting times for services Time to diagnosis or identification of a familial risk Time to treatment (risk reducing) Access to clinical trials

Configuration of services

Configuration of services

Review question

Introduction

Summary of the protocol

Table 1

Methods and process

Effectiveness/ Service delivery evidence

Included studies

Excluded studies

Summary of included studies

Table 2

Summary of the evidence

Women with ovarian cancer

Mainstream germline genetic testing program versus cancer genetic service

Mainstreaming genetic counselling versus standard genetics referral pathway

Streamlined pre-test genetic education and genetic panel testing versus standard counselling and testing

Gynaecologic oncologist-initiated genetic testing model versus traditional genetics referral

Embedded genetic counsellor in the medical and gynaecologic oncology clinic versus standard clinic

Genetics embedded model versus no genetic embedded model

Collaborative care model versus no collaborative care model

Reflex BRCA1/2 testing versus no reflex testing

Women with breast cancer

Nurse-led mainstreaming cancer genetics (MCG) service verses pre-MCG service

BRCA1/2 carriers

Multidisciplinary one-stop follow-up clinic verses no one-stop clinic

Economic evidence

Included studies

Excluded studies

Summary of included economic evidence

Economic model

Evidence statements

Economic

The committee’s discussion and interpretation of the evidence

The outcomes that matter most

The quality of the evidence

Benefits and harms

Commissioners and services providers in all settings

Primary care services

Genetic services

Gynaecology oncology multidisciplinary team

Familial ovarian cancer multidisciplinary team

Cost effectiveness and resource use

Other factors the committee took into account

Recommendations supported by this evidence review

References – included studies

Effectiveness

References - other

Appendices

Appendix A. Review protocol

Appendix B. Literature search strategies

Appendix C. Effectiveness/Service delivery evidence study selection

Appendix D. Evidence tables

Appendix E. Forest plots

Forest plots for review question: What is the most effective configuration of services for referral, risk assessment and risk management for women at increased risk of ovarian cancer (including fertility, menopause and psychological support services)?

Appendix F. GRADE tables

Appendix G. Economic evidence study selection

Study selection for: What is the most effective configuration of services for referral, risk assessment and risk management for women at increased risk of ovarian cancer (including fertility, menopause and psychological support services)?

Appendix H. Economic evidence tables

Economic evidence tables for review question: What is the most effective configuration of services for referral, risk assessment and risk management for women at increased risk of ovarian cancer (including fertility, menopause and psychological support services)?

Appendix I. Economic model

Economic model for review question: What is the most effective configuration of services for referral, risk assessment and risk management for women at increased risk of ovarian cancer (including fertility, menopause and psychological support services)?

Appendix J. Excluded studies

Excluded studies for review question: What is the most effective configuration of services for referral, risk assessment and risk management for women at increased risk of ovarian cancer (including fertility, menopause and psychological support services)?

Excluded effectiveness/ service delivery studies

Table 14

Excluded economic studies

Appendix K. Research recommendations – full details

Research recommendations for review question: What is the most effective configuration of services for referral, risk assessment and risk management for women at increased risk of ovarian cancer (including fertility, menopause and psychological support services)?

Table 1Summary of the protocol (PICO table)

Table 2Summary of included studies

Table 14Excluded studies and reasons for their exclusion