PEARL Study (Prolonged Effects of Assisted reproductive technologies on the health of women and their children: a Record Linkage study for England) (CPRD-HFEA linkage project)

The extension to the data sharing agreement is to process the data that NHS Digital are yet to supply as a data linkage service as a trusted third party.

The data processor is Department of Health and Social Care.

The Clinical Practice Research Data-linkage (CPRD) is a centre of the Medicines and Healthcare products Regulatory Agency (MHRA), an executive agency of the Department of Health & Social Care (DHSC). The MHRA regulates medicines, medical devices and blood components for transfusion in the UK and the MHRA act as the Executive agency.

CPRD is the UK’s pre-eminent research service, providing access to primary care data (that has been de-identified) linked by NHS Digital to other similarly pseudonymised health data. This data is provided by NHS Digital and others for the purposes of public health research including the monitoring of drug safety. All such data is linked (in its identifiable form) by NHS Digital only. It is jointly funded by the MHRA and the National Institute for Health Research (NIHR).

CPRD’s aims are to support vital public health research and to inform advances in patient safety in the delivery of patient care pathways. These depend on access to accurate, real-time representative patient data to produce reliable evidence based clinical and drug safety guidance. The legal bases for processing the data provided by NHS Digital are:

• Gathering of GP patient data and collation with other data sets to produce data-sets that have been de-identified: medical research under Article 9(2)(j); drug and device safety under Article 9(2)(i) of the General Data Protection Regulation

CPRD services are designed to maximise the way de-identified NHS clinical data can be used to improve and safeguard public health. For more than 20 years data provided by CPRD have been used in a range of drug safety and epidemiological studies that have impacted on health care and resulted in over 1700 peer-reviewed publications. In addition to supporting high-quality observational research, CPRD is developing world-leading services based on using real world data to support clinical trials and intervention studies. The intention is to continue to link CPRD primary care data to NHS Digital’s secondary care and other datasets, as linkage greatly increases the scale, depth, completeness and therefore value of data available for public health research. The outputs of such research based on linked data in turn improve and protect patient care pathways/treatments and provide clinical benefits for the UK, supporting delivery of CPRD’s core objectives.

CPRD’s research and data services are based on a database of de-identified longitudinal primary care records contributed by consenting GP practices from the four UK nations, and on the ability to link primary care data to secondary care data (and other data sets), from the NHS, Office of National Statistics (ONS) and Public Health England (PHE). One of CPRD’s main priorities is to increase the number of national data sets that are linked to primary care data and made available on a routine basis to the research community.

NHS Digital has been providing secondary and other data for linkage with CPRD primary care data for a number of years. Data linkage is carried out exclusively by NHS Digital as the Trusted Third Party (TTP) for this purpose. Linked data sets currently available include extracts from Civil Registration data; Hospital Episode Statistics (HES), which encompasses Admitted Patient Care, Critical Care, Outpatient and Accident & Emergency data; Patient Reported Outcome Measures (PROMs); Diagnostic Imaging Dataset (DID); Mental Health data; National Cancer Registry; Deprivation data including Townsend Score and Index of Multiple Deprivation. Critical care is supplied as a separate dataset by NHS Digital but is integrated with Admitted Patient Care.

Data can only be used for public health research purposes in research recommended for approval by ISAC for MHRA database research. CPRD make the final decision on access and ensure compliance with NHS Digital’s requirements within the data sharing agreement, e.g. security of the third party. Access to CPRD data and services will not be permitted in circumstances that may result in loss of public trust or for activities that may undermine the integrity of the CPRD database.

This application is to support a research project, which involves linkage of record level data from the Clinical Practice Research Datalink (CPRD), and the Human Fertilisation and Embryology Authority (HFEA).

The study is funded by the Medial Research Council until 31/08/2020.

The study is presented below:

The PEARL study (Prolonged Effects of Assisted reproductive technologies on the health of women and their children: a Record Linkage study for England)

The aim of this project is to create a linked dataset between HFEA infertility data and health data from the Clinical Practice Research Datalink (CPRD) mother-baby track, and to use the linked dataset to assess the effect of assisted reproductive technologies (ART) on the health of women and their children after successful fertility treatment. Specific objectives are:

1. To estimate the effect of subfertility, ovulation induction (OI) and ART on the health and development of children to adolescence [hypothesis: children born after subfertility, OI or ART experience poorer health and developmental outcomes to adolescence than their naturally conceived peers].

2. To examine the impact of subfertility, OI and successful ART on the health and wellbeing of infertile women [hypothesis: Women who have had subfertility, OI and successful ART experience different mental health trajectories to those who conceived naturally].

3. To quantify the additional resources, if any, used by women and their children after successful ART [hypothesis: Mother-baby pairs formed after successful ART make greater use of the health services and incur additional costs, compared to the mother-baby pairs formed after natural conception].

4. To assess the impact of low consent rates after September 2009, on the results of ART studies conducted using the HFEA register, and explore techniques to deal with the effects of the missing data and the impact of the potential bias [hypothesis: low consent rates since Sept 2009 adversely impact the validity of the aetiological research conducted using this dataset].

The study is an observational epidemiological study, which will use a retrospective cohort design. Data for the study will be linked between CPRD and the Human Fertilisation and Embryology Authority (HFEA). PEARL links health data (from the Mother-Baby track of CPRD GOLD), to information collected about all assisted reproductive technology (ART) cycles in England (from the Human Fertilisation and Embryology Authority Register). Approximately 460,000 mother-baby dyads based in English GP practices, with a valid NHS number and consent to link data, are included in the CPRD mother-baby dataset for the period 1991-Sept 2009. Estimates based on 1.5% of babies resulting from ART, 95% successful matching between HFEA and CPRD, 61% with continuous follow up of 4-22 years, gives 3933 ART dyads and 262,571 comparison dyads. Different indicators will be used to divide the mothers in the CPRD mother-baby dataset to identify those with no records for fertility consultations (fertile comparison group), those with a record of consulting the doctor about fertility and use evidence of consultations for fertility problems or investigations as a means to identify those who may be subfertile. The fertile comparison group includes both unplanned and planned pregnancies.

Methodological work to assess the impact of low consent rates after September 2009, on the results of ART studies conducted using the HFEA register and explore techniques to deal with the effects of the missing data will also be conducted. Data are required for the period 1991-2018.

Mother-baby pairs will be grouped depending on their exposure to ART, based on both primary care and HFEA records, and outcomes will be compared in those children born with and without the use of ART, and their mothers. Multivariable regression analysis will be used, and the role of confounders and effect modifiers in explaining any observed effects between exposure and outcomes will be explored. The cohort design takes maximum advantage of the longitudinal nature of the data, and the available sample, while being most suitable for a relatively rare exposure (ART) and more common outcomes. It is anticipated that the final cohort will be just under 270,000, with 3933 assisted conceptions.

CPRD already hold NHS Digital data disseminated under NIC-15625, which includes HES data, Mental Health data, Diagnostic Imaging data, mortality data and Patient Reported Outcome Measures. This data is linked to the patient identifiers sent to NHS Digital by the GP system suppliers. No patient identifiable data is sent to CPRD, only study ids that enable them to link the NHS Digital data to the GP data. The PEARL study will use the data from HFEA and the Mother-Baby track of CPRD GOLD, this includes mothers that have had fertility treatment and mothers that have no records for fertility consultations, it is this second group that will be used as the fertile comparison group. Routine data will be collected up to 31 December 2017.

The legal basis for the study comprises of the following components:

1) The processing of the HFEA data by NHS Digital and CPRD are considered outsourced functions of the HFEA, and thus are covered by Section 8D of the HFE Act (1990), which grants the HFEA the power to contract out functions and disclose information where the function of the HFEA is exercised by others.

2) Study specific Section 251 approval (ref: 16/CAG/0053) allows the flow of CPRD identifiers to NHS Digital for the purposes of linkage, and the linkage of CPRD identifiers to HFEA identifiers without consent (this applies to pre-2009 HFEA data, as consent was not sought prior to 2010).

3) Where broad consent for research use was sought (HFEA data since 2009), and consent was given, it is recognised that they do not fulfil the GDPR consent requirements, however, the consent forms meet the Common Law Duty of Confidentiality. The governance landscape has changed since these consent forms were drafted, but there would be a reasonable expectation among those who signed the consent forms that people who work with the databases (which are mentioned) would use identifiers for the linkage process. It is not possible to contact all those who consented to the use of data to update their consents (nor would it be appropriate, since they consented to non-contact research use of their data). The identifiable data that is used in processing and linkage are held only by the HFEA and by NHS Digital. Identifiable data will not be released to either the CPRD or the study team at the University of Oxford. The use of the data that has been de-identified will provide robust scientific evidence regarding the long term health outcomes for women and children after fertility treatment, which is in the public interest (as evidenced by the provision of Section 251 for the data for which there is not consent available).

4) University of Oxford have support for the study under section 251 of the NHS Act 2006 16/CAG/0053. SD5.2 - SD5.6 provide the detail of the support for name, NHS number, postcode, date of birth/date of death and link to mother baby data already held by HSCIC for 1999-2009 data only for English patients only. The scope of the s251 support is to cover the processing of confidential patient information within NHS Digital. The disclosure of HFEA data to NHS Digital is permissible under the HFEA regulations.

The Human Fertilisation and Embryology Authority (HFEA) are permitted under the Human Fertilisation and Embryology Act 1990, Section 33D to enable the common law duty of confidentiality to be temporarily lifted so that confidential patient information can be transferred from the HFEA to NHS Digital without the disclosure being in breach of the common law duty of confidentiality.

(1) Regulations may—

a. (a)make such provision for and in connection with requiring or regulating the processing of protected information for the purposes of medical research as the Secretary of State considers is necessary or expedient in the public interest or in the interests of improving patient care, and

b. (b)make such provision for and in connection with requiring or regulating the processing of protected information for the purposes of any other research as the Secretary of State considers is necessary or expedient in the public interest.

(3) Where regulations under subsection (1) require or regulate the processing of protected information for the purposes of medical research, such regulations may enable any approval given under regulations made under section 251 of the National Health Service Act 2006 (control of patient information) to have effect for the purposes of the regulations under subsection (1) in their application to England and Wales.

The legal basis under GDPR for the processing and storage of personal data for PEARL is that it is ‘a task in the public interest’ (article 6 (1) (e)) and that sensitive personal data is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes (article 9 (2) (j), based on Article 89(1).

Data analysis will commence as soon as the linked datasets are received and is expected to be finished within 24 months of the release of the bespoke dataset. Data will not be used for sales and marketing purposes. All outputs will contain only data that is aggregated with small numbers suppressed in line with the HES Analysis Guide.

Research reports will be prepared for the funder (MRC), Research Ethics Committee, Confidentiality Advisory Group and HFEA, with a final report outlining the key finding submitted within one year of study completion. A report will be produced for the HFEA which: summarizes the results of the analyses of outcomes in the mothers and their children based on the linked data; describes the impact of non-consent in the HFEA data and how this can be addressed. University of Oxford will also have a summary of the study results on their website. The final reports are expected as soon as results from the studies are available.

The outputs will be peer-reviewed scientific journal articles, presentations (at scientific conferences and to other audiences) and reports as outlined below. All outputs will contain only aggregate level data with small numbers suppressed in line with HES analysis guide.

It is anticipated that 4-5 peer-reviewed articles will be published between mid-2019 and the end of 2020, including papers that focus on child health outcomes, maternal mental health, the long-term economic costs of fertility treatments, and methodological considerations of using these data. High impact journals will be selected with the target audience in mind for example, the analysis of economic costs and analysis of mothers’ mental health will be of interest to different professional and academic groups and the selected accordingly.

Target journals include: New England Journal of Medicine, British Medical Journal, International Journal of Epidemiology, and all accepted papers will be open access publications to ensure free availability to all readers internationally. The PEARL team will liaise with the University of Oxford departmental communications office regarding the dissemination of findings. This will ensure that the media are informed of the results, so that the widest audience can be reached. This will include the writing of a press release, and a pre-recorded video interview with the study lead. At the end of the study, the video interviews will be collated into a podcast to be made freely available on the PEARL website (early 2021).

Findings from the study will be presented at appropriate scientific conferences (e.g. European Society of Human Reproduction and Embryology, 36th meeting, in June 2020, or World Congress of Epidemiology in 2020). This will include poster presentations and short talks to expert audiences.

A lay summary of the key findings, with links to published papers, will be produced by the end of 2021. This will be circulated to interested parties (e.g. charities, ART clinics involved in the qualitative survey), and will also be posted on the National Perinatal Epidemiology Unit (NPEU) website where it can be accessed by the general public. This summary will also be supported by an infographic communicating the main findings and implications for women and children born through treatment. The infographic will be developed by the NPEUs experienced in-house design team. The PEARL researchers will work with the University of Oxford departmental communications team to disseminate to a wider audience via blog posts, the university video wall, and media interviews etc. The research findings will also be communicated to the wider lay community through social media such as Twitter and Facebook.

In 2020 researchers from the University of Oxford will arrange a one-day workshop for researchers who use, or are interested in using, CPRD fertility or HFEA registry data. University of Oxford will take this opportunity to present key findings as part of the proceedings.

Data not yet linked so no yielded benefit to date.

The data controller is Department of Health and Social Care, with the Secretary of State for Health and Social Care (acting as part of the Crown), acting through the Clinical Practice Research Datalink centre (hereinafter referred to as CPRD) within the Medicines and Healthcare Products Regulatory Agency. This is the same arrangement for the data processor in that it is Department of Health and Social Care although it is CPRD who process the data but are not listed as data processors because they are not a legal entity.

The data processor is Department of Health and Social Care.

The Clinical Practice Research Data-linkage (CPRD) is a centre of the Medicines and Healthcare products Regulatory Agency (MHRA), an executive agency of the Department of Health & Social Care (DHSC). The MHRA regulates medicines, medical devices and blood components for transfusion in the UK and the MHRA act as the Executive agency.

CPRD is the UK’s pre-eminent research service, providing access to primary care data (that has been de-identified) linked by NHS Digital to other similarly pseudonymised health data. This data is provided by NHS Digital and others for the purposes of public health research including the monitoring of drug safety. All such data is linked (in its identifiable form) by NHS Digital only. It is jointly funded by the MHRA and the National Institute for Health Research (NIHR).

CPRD’s aims are to support vital public health research and to inform advances in patient safety in the delivery of patient care pathways. These depend on access to accurate, real-time representative patient data to produce reliable evidence based clinical and drug safety guidance. The legal bases for processing the data provided by NHS Digital are:

• Gathering of GP patient data and collation with other data sets to produce data-sets that have been de-identified: medical research under Article 9(2)(j); drug and device safety under Article 9(2)(i) of the General Data Protection Regulation

CPRD services are designed to maximise the way de-identified NHS clinical data can be used to improve and safeguard public health. For more than 20 years data provided by CPRD have been used in a range of drug safety and epidemiological studies that have impacted on health care and resulted in over 1700 peer-reviewed publications. In addition to supporting high-quality observational research, CPRD is developing world-leading services based on using real world data to support clinical trials and intervention studies. The intention is to continue to link CPRD primary care data to NHS Digital’s secondary care and other datasets, as linkage greatly increases the scale, depth, completeness and therefore value of data available for public health research. The outputs of such research based on linked data in turn improve and protect patient care pathways/treatments and provide clinical benefits for the UK, supporting delivery of CPRD’s core objectives.

CPRD’s research and data services are based on a database of de-identified longitudinal primary care records contributed by consenting GP practices from the four UK nations, and on the ability to link primary care data to secondary care data (and other data sets), from the NHS, Office of National Statistics (ONS) and Public Health England (PHE). One of CPRD’s main priorities is to increase the number of national data sets that are linked to primary care data and made available on a routine basis to the research community.

NHS Digital has been providing secondary and other data for linkage with CPRD primary care data for a number of years. Data linkage is carried out exclusively by NHS Digital as the Trusted Third Party (TTP) for this purpose. Linked data sets currently available include extracts from Civil Registration data; Hospital Episode Statistics (HES), which encompasses Admitted Patient Care, Critical Care, Outpatient and Accident & Emergency data; Patient Reported Outcome Measures (PROMs); Diagnostic Imaging Dataset (DID); Mental Health data; National Cancer Registry; Deprivation data including Townsend Score and Index of Multiple Deprivation. Critical care is supplied as a separate dataset by NHS Digital but is integrated with Admitted Patient Care.

Data can only be used for public health research purposes in research recommended for approval by ISAC for MHRA database research. CPRD make the final decision on access and ensure compliance with NHS Digital’s requirements within the data sharing agreement, e.g. security of the third party. Access to CPRD data and services will not be permitted in circumstances that may result in loss of public trust or for activities that may undermine the integrity of the CPRD database.

This application is to support a research project, which involves linkage of record level data from the Clinical Practice Research Datalink (CPRD), and the Human Fertilisation and Embryology Authority (HFEA).

The study is funded by the Medial Research Council until 31/08/2020.

The study is presented below:

The PEARL study (Prolonged Effects of Assisted reproductive technologies on the health of women and their children: a Record Linkage study for England)

The aim of this project is to create a linked dataset between HFEA infertility data and health data from the Clinical Practice Research Datalink (CPRD) mother-baby track, and to use the linked dataset to assess the effect of assisted reproductive technologies (ART) on the health of women and their children after successful fertility treatment. Specific objectives are:

1. To estimate the effect of subfertility, ovulation induction (OI) and ART on the health and development of children to adolescence [hypothesis: children born after subfertility, OI or ART experience poorer health and developmental outcomes to adolescence than their naturally conceived peers].

2. To examine the impact of subfertility, OI and successful ART on the health and wellbeing of infertile women [hypothesis: Women who have had subfertility, OI and successful ART experience different mental health trajectories to those who conceived naturally].

3. To quantify the additional resources, if any, used by women and their children after successful ART [hypothesis: Mother-baby pairs formed after successful ART make greater use of the health services and incur additional costs, compared to the mother-baby pairs formed after natural conception].

4. To assess the impact of low consent rates after September 2009, on the results of ART studies conducted using the HFEA register, and explore techniques to deal with the effects of the missing data and the impact of the potential bias [hypothesis: low consent rates since Sept 2009 adversely impact the validity of the aetiological research conducted using this dataset].

The study is an observational epidemiological study, which will use a retrospective cohort design. Data for the study will be linked between CPRD and the Human Fertilisation and Embryology Authority (HFEA). PEARL links health data (from the Mother-Baby track of CPRD GOLD), to information collected about all assisted reproductive technology (ART) cycles in England (from the Human Fertilisation and Embryology Authority Register). Approximately 460,000 mother-baby dyads based in English GP practices, with a valid NHS number and consent to link data, are included in the CPRD mother-baby dataset for the period 1991-Sept 2009. Estimates based on 1.5% of babies resulting from ART, 95% successful matching between HFEA and CPRD, 61% with continuous follow up of 4-22 years, gives 3933 ART dyads and 262,571 comparison dyads. Different indicators will be used to divide the mothers in the CPRD mother-baby dataset to identify those with no records for fertility consultations (fertile comparison group), those with a record of consulting the doctor about fertility and use evidence of consultations for fertility problems or investigations as a means to identify those who may be subfertile. The fertile comparison group includes both unplanned and planned pregnancies.

Methodological work to assess the impact of low consent rates after September 2009, on the results of ART studies conducted using the HFEA register and explore techniques to deal with the effects of the missing data will also be conducted. Data are required for the period 1991-2018.

Mother-baby pairs will be grouped depending on their exposure to ART, based on both primary care and HFEA records, and outcomes will be compared in those children born with and without the use of ART, and their mothers. Multivariable regression analysis will be used, and the role of confounders and effect modifiers in explaining any observed effects between exposure and outcomes will be explored. The cohort design takes maximum advantage of the longitudinal nature of the data, and the available sample, while being most suitable for a relatively rare exposure (ART) and more common outcomes. It is anticipated that the final cohort will be just under 270,000, with 3933 assisted conceptions.

CPRD already hold NHS Digital data disseminated under NIC-15625, which includes HES data, Mental Health data, Diagnostic Imaging data, mortality data and Patient Reported Outcome Measures. This data is linked to the patient identifiers sent to NHS Digital by the GP system suppliers. No patient identifiable data is sent to CPRD, only study ids that enable them to link the NHS Digital data to the GP data. The PEARL study will use the data from HFEA and the Mother-Baby track of CPRD GOLD, this includes mothers that have had fertility treatment and mothers that have no records for fertility consultations, it is this second group that will be used as the fertile comparison group. Routine data will be collected up to 31 December 2017.

The legal basis for the study comprises of the following components:

1) The processing of the HFEA data by NHS Digital and CPRD are considered outsourced functions of the HFEA, and thus are covered by Section 8D of the HFE Act (1990), which grants the HFEA the power to contract out functions and disclose information where the function of the HFEA is exercised by others.

2) Study specific Section 251 approval (ref: 16/CAG/0053) allows the flow of CPRD identifiers to NHS Digital for the purposes of linkage, and the linkage of CPRD identifiers to HFEA identifiers without consent (this applies to pre-2009 HFEA data, as consent was not sought prior to 2010).

3) Where broad consent for research use was sought (HFEA data since 2009), and consent was given, it is recognised that they do not fulfil the GDPR consent requirements, however, the consent forms meet the Common Law Duty of Confidentiality. The governance landscape has changed since these consent forms were drafted, but there would be a reasonable expectation among those who signed the consent forms that people who work with the databases (which are mentioned) would use identifiers for the linkage process. It is not possible to contact all those who consented to the use of data to update their consents (nor would it be appropriate, since they consented to non-contact research use of their data). The identifiable data that is used in processing and linkage are held only by the HFEA and by NHS Digital. Identifiable data will not be released to either the CPRD or the study team at the University of Oxford. The use of the data that has been de-identified will provide robust scientific evidence regarding the long term health outcomes for women and children after fertility treatment, which is in the public interest (as evidenced by the provision of Section 251 for the data for which there is not consent available).

4) University of Oxford have support for the study under section 251 of the NHS Act 2006 16/CAG/0053. SD5.2 - SD5.6 provide the detail of the support for name, NHS number, postcode, date of birth/date of death and link to mother baby data already held by HSCIC for 1999-2009 data only for English patients only. The scope of the s251 support is to cover the processing of confidential patient information within NHS Digital. The disclosure of HFEA data to NHS Digital is permissible under the HFEA regulations.

The Human Fertilisation and Embryology Authority (HFEA) are permitted under the Human Fertilisation and Embryology Act 1990, Section 33D to enable the common law duty of confidentiality to be temporarily lifted so that confidential patient information can be transferred from the HFEA to NHS Digital without the disclosure being in breach of the common law duty of confidentiality.

(1) Regulations may—

a. (a)make such provision for and in connection with requiring or regulating the processing of protected information for the purposes of medical research as the Secretary of State considers is necessary or expedient in the public interest or in the interests of improving patient care, and

b. (b)make such provision for and in connection with requiring or regulating the processing of protected information for the purposes of any other research as the Secretary of State considers is necessary or expedient in the public interest.

(3) Where regulations under subsection (1) require or regulate the processing of protected information for the purposes of medical research, such regulations may enable any approval given under regulations made under section 251 of the National Health Service Act 2006 (control of patient information) to have effect for the purposes of the regulations under subsection (1) in their application to England and Wales.

The legal basis under GDPR for the processing and storage of personal data for PEARL is that it is ‘a task in the public interest’ (article 6 (1) (e)) and that sensitive personal data is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes (article 9 (2) (j), based on Article 89(1).

Data analysis will commence as soon as the linked datasets are received and is expected to be finished within 24 months of the release of the bespoke dataset. Data will not be used for sales and marketing purposes. All outputs will contain only data that is aggregated with small numbers suppressed in line with the HES Analysis Guide.

Research reports will be prepared for the funder (MRC), Research Ethics Committee, Confidentiality Advisory Group and HFEA, with a final report outlining the key finding submitted within one year of study completion. A report will be produced for the HFEA which: summarizes the results of the analyses of outcomes in the mothers and their children based on the linked data; describes the impact of non-consent in the HFEA data and how this can be addressed. University of Oxford will also have a summary of the study results on their website. The final reports are expected as soon as results from the studies are available.

The outputs will be peer-reviewed scientific journal articles, presentations (at scientific conferences and to other audiences) and reports as outlined below. All outputs will contain only aggregate level data with small numbers suppressed in line with HES analysis guide.

It is anticipated that 4-5 peer-reviewed articles will be published between mid-2019 and the end of 2020, including papers that focus on child health outcomes, maternal mental health, the long-term economic costs of fertility treatments, and methodological considerations of using these data. High impact journals will be selected with the target audience in mind for example, the analysis of economic costs and analysis of mothers’ mental health will be of interest to different professional and academic groups and the selected accordingly.

Target journals include: New England Journal of Medicine, British Medical Journal, International Journal of Epidemiology, and all accepted papers will be open access publications to ensure free availability to all readers internationally. The PEARL team will liaise with the University of Oxford departmental communications office regarding the dissemination of findings. This will ensure that the media are informed of the results, so that the widest audience can be reached. This will include the writing of a press release, and a pre-recorded video interview with the study lead. At the end of the study, the video interviews will be collated into a podcast to be made freely available on the PEARL website (early 2021).

Findings from the study will be presented at appropriate scientific conferences (e.g. European Society of Human Reproduction and Embryology, 36th meeting, in June 2020, or World Congress of Epidemiology in 2020). This will include poster presentations and short talks to expert audiences.

A lay summary of the key findings, with links to published papers, will be produced by the end of 2021. This will be circulated to interested parties (e.g. charities, ART clinics involved in the qualitative survey), and will also be posted on the National Perinatal Epidemiology Unit (NPEU) website where it can be accessed by the general public. This summary will also be supported by an infographic communicating the main findings and implications for women and children born through treatment. The infographic will be developed by the NPEUs experienced in-house design team. The PEARL researchers will work with the University of Oxford departmental communications team to disseminate to a wider audience via blog posts, the university video wall, and media interviews etc. The research findings will also be communicated to the wider lay community through social media such as Twitter and Facebook.

In 2020 researchers from the University of Oxford will arrange a one-day workshop for researchers who use, or are interested in using, CPRD fertility or HFEA registry data. University of Oxford will take this opportunity to present key findings as part of the proceedings.

Yielded Benefits is not a requirement for new applications.