British Association of Dermatologists' Biologic and Immunomodulators Register (BADBIR)

The University of Manchester (UoM) requires Civil Registration Mortality data, Cancer Registration data, and Hospital Episode Statistics Admitted Patient Care data to fulfil British Association of Dermatologists Biologics & Immunomodulators Register (BADBIR) study’s aim of assessing the long term safety of new treatments for psoriasis. Primary endpoints for this safety objective include malignancy, infections requiring hospitalisation, death and any other serious adverse event. Linkage data ensures that the capture of Serious Adverse Events on the study population is maximised. The data requested has been minimised to a cohort, currently of around 14,500 participants, although this is added to on an annual basis as more participants consent to the study. Latest Identifiers, Supplied Identifiers and NHS Number supplied previously have since been removed to further minimise the data request. Only data that is needed to achieve the purpose described in this agreement has been requested.

The project has been running since 2007 and collects data from Dermatology departments in NHS Hospital Trusts, which is stored on a web-based system as a register. Data is used to analyse the long-term effect of biologic treatments for short/long term safety of patients. Malignancy and death data are used to confirm patients that may no longer appear on the Register and to ascertain the safety and risk of biologic interventions.

Under previous iterations of this Agreement, mortality and cancer reports were provided by NHS England to the University of Manchester on a 4-monthly basis (3 times a year), with HES APC data annually. Going forward, all datasets will be disseminated annually. The purpose for data processing has not changed as a result of the change in data frequency.

Data will be processed under GDPR Article 6 (1) (e) (processing is necessary for the performance of a task in the public interest or in the exercise of official authority vested in the controller) and Article 9 (2) (j) (processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes). This legal basis applies to both joint data controllers: the University of Manchester and the British Association of Dermatologists (BAD). The University of Manchester is an independent corporation which came into existence on 1 October 2004. It was established by royal charter on the dissolution of the Victoria University of Manchester and the University of Manchester Institute of Science and Technology (UMIST), both of whose rights, properties, assets and obligations were transferred to the institution by means of the University of Manchester Act (2004). The data are required for research purposes in the public interest - meeting the conditions in the DPA 2018 Schedule 1 Part 1 (4) - which GDPR Recital 52(2) determines is an appropriate derogation from the prohibition on processing special categories of personal data.

BADBIR is funded by the British Association of Dermatologists (BAD) and based at the University of Manchester (UoM) since its inception in 2007. It is an observational study which seeks to address the previously described limitations by systematically and prospectively evaluating safety in large numbers of “real world” patients receiving new treatments for psoriasis over a prolonged period compared to a comparator/control cohort. This type of register is considered to be the current gold standard in evaluating long-term treatment safety. This is achieved by following consented, registered participants and collecting information on drug exposure and adverse events (AEs). Therefore, a more reliable and valid picture of long-term safety can be provided to clinicians and patients.

The British Association of Dermatologists are a joint data controller alongside the University of Manchester. Together, the parties jointly set the study protocol. It is solely the University of Manchester who store and process data received by NHS England.

The data subjects are patients with moderate-to-severe psoriasis starting on a systemic treatment (i.e., tablet or injection) for their disease. Depending on the type of treatment being received, patients consent to be registered to one of three study cohorts (biologic, small molecule, or conventional therapy).

The BADBIR study registers participants from almost all dermatology outpatients departments in the NHS across the UK. Flagging with NHS England is therefore required for participants spread across England and Wales. Participants from Scotland and Northern Ireland have linkage with their respective national providers of healthcare data outside of this application.

Psoriasis is a chronic disease and there is interest in the long-term safety outcomes of patients exposed to these new immunosuppressant therapies. As such, all participants continue to be observed, even if therapy is stopped or changed.

The University of Manchester collects data on study participants from dermatology departments. The three datasets (Mortality, Cancers and Hospital Episode Statistics) provided via NHS England comprise serious adverse event (SAE) information. This is of particular importance where participants are lost-to-follow-up or not attending dermatology reviews as scheduled. The information received will be linked with other BADBIR study data via a common pseudo-ID. Both medical history and prospective data are relevant for BADBIR’s safety assessment thus a range of years have been requested across the NHS England datasets.

Patients with psoriasis often require lifelong treatment, which may expose them to toxic and potentially fatal side-effects. Biologics, and more recently, small molecule immunotherapies, have been licensed for the treatment of moderate to severe psoriasis. Despite the rigorous evaluation of efficacy and safety of these interventions, the evidence is based primarily on randomised placebo-controlled trials (RCTs) that are powered to detect differences in efficacy rather than to identify rare side-effects, or modest increase in risk of a common co-morbidity such as cardiovascular disease. These RCTs tend to have short placebo-controlled periods of about 12 weeks and so may not detect side-effects related to long-term use. In addition, RCTs have exclusion criteria (such as co-morbidities relevant to psoriasis) that may limit the ability to generalise the results to clinical practice. These drugs offer considerable benefits in safety and quality of life for those with moderate to severe psoriasis, but questions remain regarding long-term safety, safety in particular circumstances (e.g., pregnancy and childhood, optimal treatment sequence, relative drug survival, and the use of co-therapies).

In the UK, voluntary spontaneous adverse event (AE) reporting is undertaken via the “Yellow Card” System. However, whilst useful for identifying rare events, it is rarely complete, and therefore provides only limited information concerning the frequency of adverse reactions or their causality. Other sources of post-marketing safety information such as open label extensions to clinical trials may be subject to limitations, including survival bias, lack of a comparator group, and lack of follow up on patients who cycle through various therapies.

Since the study’s inception in 2007, the register has obtained informed patient consent of over 13,600 individuals and continues to recruit roughly 1,000 participants per year. Participants were provided consent information which explains the sharing of identifiers with NHS England (under its predecessor name at the time) for the release of mortality and cancer data should they occur to the University of Manchester. In 2017, the study obtained s251 support for the release of HES data for those individuals who consented under version 1 to 4. Since 11/09/2017, any new participants will be consenting (under version 5 or later) to the release of mortality, cancer, and HES from NHS England. The University of Manchester therefore relies on a mixture of Informed Patient Consent and section 251 support of the NHS Act 2006 to address the Duty of Confidentiality.

Note that there is no age restriction in the eligibility criteria in the BADBIR protocol meaning psoriasis patients under the age of 16 can enter the study. These patients will sign Assent with separate Parent/Guardian Consent provided to allow registration. As these participants reach the age of 16, it is requested new Consent is provided as per new adult recruits. As an observational study, all BADBIR participants are under the care of a dermatologist thus the updated consent will be obtained by the clinical or research teams locally. Patients will only be flagged with NHS England once the updated consent is in place (i.e. if only Assent and Parent/Guardian Consent, patient will not be flagged).

Publication of the results of analyses is ongoing. Results of the analyses are presented at relevant national and international scientific meetings, such as the British Association of Dermatologists, American Academy of Dermatology, International Conference on Pharmacoepidemiology (ICPE) and in peer reviewed journals e.g. British Journal of Dermatology (BJD), Journal of Investigative Dermatology (JID), JAMA Dermatology.

These will be targeted to ensure that the results are disseminated widely among the dermatology and the research community, including and the UK Dermatology Clinical Trials Network.

There has been a number of publications using BADBIR data in peer-reviewed journals to date. Most of these papers have also been presented at local, regional and international medical, nursing, scientific and patient conferences thus informing evidenced based clinical care. In addition, this “real world” experience of safety and effectiveness of these drugs will contribute to national guidelines of management of psoriasis e.g. NICE.

Studies with safety outcomes have recently been published including Risk of Major Cardiovascular Events in Patients With Psoriasis Receiving Biologic Therapies and an analysis of Risks of basal cell and squamous cell carcinoma in psoriasis patients. Both were published in the Journal of European Academy of Dermatology and Venereology in 2020 and 2021 respectively.

The up to date list of all publications arising from BADBIR data is posted on the BADBIR website (http://www.badbir.org)

It is expected that other papers will be published shortly including: incidence of suicide in the BABDIR population, rates of solid tumour in patients receiving biologic therapy compared to conventional systemic therapy and an investigation of the pathogenesis of paradoxical atopic eczema occurring in psoriasis patients on biologics. A research grant has been obtained from the Psoriasis Association which will explore the risks associated with switching between originator and biosimilar medications amongst other outcomes. It is anticipated that this analysis will be undertaken across 2021 and 2022.

All outputs will contain only data that is aggregated with small numbers suppressed in line with the HES Analysis Guide.

Six-monthly summary reports are provided to the BADBIR Data Monitoring Committee to include crude unadjusted rates of specific events of interests. Should a safety signal be identified, then further analysis can be requested and in the event of a significant concern the wider dermatology community will be informed. In addition, this “real world” experience of safety and effectiveness of these drugs will contribute to national guidelines of management of psoriasis e.g. NICE and thereby to the clinical management of patients with psoriasis.

A yearly Participant (patient) Newsletter which includes a summary of any published paper is also provided via the BADBIR website and the recruiting dermatology centres. YouTube and Twitter have also been used to disseminate information on BADBIR including two presentations at the Psoriasis Association annual meetings.

Data dissemination is managed by a data writing group who are responsible to the BADBIR Steering Committee. This group comprises of dermatologists, research scientists, dermatology nurses and patients with psoriasis and guide the potential for output for disseminated data to provide a measurable benefit.

The BADBIR Steering Committee is comprised of representatives of the data controller and will therefore contribute to this responsibility.

Published data will help clinicians and patients make more informed decisions about psoriasis treatment options. The following paragraphs outline the overall published benefits of BADBIR to date (i.e. not solely attributeable to NHS Digital data). These publications have provided more confidence to prescribers in best use of new biologic medications for treatment of psoriasis. It is hoped NHS Digital data will contribute significantly to the data analysis of BADBIR and help strengthen this confidence further.

There have been three publications in high impact journals on drug effectiveness. One paper concerned the length of time patients typically stay on biologic treatments when received as treatment for psoriasis. Biologics in clinical practice have a good overall survival rate in psoriasis patients but decrease over time; ustekinumab had the highest first-course drug survival in biologic-naive patients, followed by adalimumab. A paper followed which looked at duration of treatment for patients prescribed a second biologic therapy for psoriasis. This found that 77% of patients who were switched to a second biologic continued on the new treatment for at least 12 months. This shows clearly that patients experiencing treatment failure with one biologic therapy can benefit from switching to another. The results of this study should support clinical decision making when choosing second-line biologic therapy for psoriasis patients.

In 2017 a publication was made on the risk of serious infections for patients with psoriasis being treated with biologics. The University of Manchester did not find a statistically significant higher relative risk of serious infections for etanercept, adalimumab and ustekinumab as compared to non-biologic therapies for patients with psoriasis (e.g. methotrexate, ciclosporin). There was no difference in the risk of serious infections between etanercept, adalimumab and ustekinumab. The risk of serious infection, therefore, should not be a primary concern for patients and clinicians when deciding between non-biologic systemic therapies or these three biologic therapies for psoriasis.

BADBIR is monitoring drug safety over time and will look at lots of outcomes including heart conditions and cancer. The study has therefore analysed data to provide reassurance to prescribers that the treatments are safe in these outcomes researched. Risk of Major Cardiovascular Events (MACE) is not increased in patients with Psoriasis receiving Biologic Therapies. Also, BADBIR research has indicated there is no enhanced risks of developing two types of skin cancer (a basal cell or squamous cell carcinoma) by being treated with a biologic vs a conventional psoriasis drug.

There are no direct benefits for participants in BADBIR but the publications that arise from the project will contribute to the knowledge on the long-term safety of these new treatments thus benefiting patients in the future.

The University of Manchester (UoM) requires Civil Registration Mortality data, Cancer Registration data, and Hospital Episode Statistics Admitted Patient Care data to fulfil British Association of Dermatologists Biologics & Immunomodulators Register (BADBIR) study’s aim of assessing the long term safety of new treatments for psoriasis. Primary endpoints for this safety objective include malignancy, infections requiring hospitalisation, death and any other serious adverse event. Linkage data ensures that the capture of Serious Adverse Events on the study population is maximised. The data requested has been minimised to a cohort, currently of around 14,500 participants, although this is added to on an annual basis as more participants consent to the study. Latest Identifiers, Supplied Identifiers and NHS Number supplied previously have since been removed to further minimise the data request. Only data that is needed to achieve the purpose described in this agreement has been requested.

The project has been running since 2007 and collects data from Dermatology departments in NHS Hospital Trusts, which is stored on a web-based system as a register. Data is used to analyse the long-term effect of biologic treatments for short/long term safety of patients. Malignancy and death data are used to confirm patients that may no longer appear on the Register and to ascertain the safety and risk of biologic interventions.

Under previous iterations of this Agreement, mortality and cancer reports were provided by NHS Digital to the University of Manchester on a 4-monthly basis (3 times a year), with HES APC data annually. Going forward, all datasets will be disseminated annually. The purpose for data processing has not changed as a result of the change in data frequency.

Data will be processed under GDPR Article 6 (1) (e) (processing is necessary for the performance of a task in the public interest or in the exercise of official authority vested in the controller) and Article 9 (2) (j) (processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes). This legal basis applies to both joint data controllers: the University of Manchester and the British Association of Dermatologists (BAD). The University of Manchester is an independent corporation which came into existence on 1 October 2004. It was established by royal charter on the dissolution of the Victoria University of Manchester and the University of Manchester Institute of Science and Technology (UMIST), both of whose rights, properties, assets and obligations were transferred to the institution by means of the University of Manchester Act (2004). The data are required for research purposes in the public interest - meeting the conditions in the DPA 2018 Schedule 1 Part 1 (4) - which GDPR Recital 52(2) determines is an appropriate derogation from the prohibition on processing special categories of personal data.

BADBIR is funded by the British Association of Dermatologists (BAD) and based at the University of Manchester (UoM) since its inception in 2007. It is an observational study which seeks to address the previously described limitations by systematically and prospectively evaluating safety in large numbers of “real world” patients receiving new treatments for psoriasis over a prolonged period compared to a comparator/control cohort. This type of register is considered to be the current gold standard in evaluating long-term treatment safety. This is achieved by following consented, registered participants and collecting information on drug exposure and adverse events (AEs). Therefore, a more reliable and valid picture of long-term safety can be provided to clinicians and patients.

The British Association of Dermatologists are a joint data controller alongside the University of Manchester. Together, the parties jointly set the study protocol. It is solely the University of Manchester who store and process data received by NHS Digital.

The data subjects are patients with moderate-to-severe psoriasis starting on a systemic treatment (i.e., tablet or injection) for their disease. Depending on the type of treatment being received, patients consent to be registered to one of three study cohorts (biologic, small molecule, or conventional therapy).

The BADBIR study registers participants from almost all dermatology outpatients departments in the NHS across the UK. Flagging with NHS Digital is therefore required for participants spread across England and Wales. Participants from Scotland and Northern Ireland have linkage with their respective national providers of healthcare data outside of this application.

Psoriasis is a chronic disease and there is interest in the long-term safety outcomes of patients exposed to these new immunosuppressant therapies. As such, all participants continue to be observed, even if therapy is stopped or changed.

The University of Manchester collects data on study participants from dermatology departments. The three datasets (Mortality, Cancers and Hospital Episode Statistics) provided via NHS Digital comprise serious adverse event (SAE) information. This is of particular importance where participants are lost-to-follow-up or not attending dermatology reviews as scheduled. The information received will be linked with other BADBIR study data via a common pseudo-ID. Both medical history and prospective data are relevant for BADBIR’s safety assessment thus a range of years have been requested across the NHS Digital datasets.

Patients with psoriasis often require lifelong treatment, which may expose them to toxic and potentially fatal side-effects. Biologics, and more recently, small molecule immunotherapies, have been licensed for the treatment of moderate to severe psoriasis. Despite the rigorous evaluation of efficacy and safety of these interventions, the evidence is based primarily on randomised placebo-controlled trials (RCTs) that are powered to detect differences in efficacy rather than to identify rare side-effects, or modest increase in risk of a common co-morbidity such as cardiovascular disease. These RCTs tend to have short placebo-controlled periods of about 12 weeks and so may not detect side-effects related to long-term use. In addition, RCTs have exclusion criteria (such as co-morbidities relevant to psoriasis) that may limit the ability to generalise the results to clinical practice. These drugs offer considerable benefits in safety and quality of life for those with moderate to severe psoriasis, but questions remain regarding long-term safety, safety in particular circumstances (e.g., pregnancy and childhood, optimal treatment sequence, relative drug survival, and the use of co-therapies).

In the UK, voluntary spontaneous adverse event (AE) reporting is undertaken via the “Yellow Card” System. However, whilst useful for identifying rare events, it is rarely complete, and therefore provides only limited information concerning the frequency of adverse reactions or their causality. Other sources of post-marketing safety information such as open label extensions to clinical trials may be subject to limitations, including survival bias, lack of a comparator group, and lack of follow up on patients who cycle through various therapies.

Since the study’s inception in 2007, the register has obtained informed patient consent of over 13,600 individuals and continues to recruit roughly 1,000 participants per year. Participants were provided consent information which explains the sharing of identifiers with NHS Digital (under its predecessor name at the time) for the release of mortality and cancer data should they occur to the University of Manchester. In 2017, the study obtained s251 support for the release of HES data for those individuals who consented under version 1 to 4. Since 11/09/2017, any new participants will be consenting (under version 5 or later) to the release of mortality, cancer, and HES from NHS Digital. The University of Manchester therefore relies on a mixture of Informed Patient Consent and section 251 support of the NHS Act 2006 to address the Duty of Confidentiality.

Note that there is no age restriction in the eligibility criteria in the BADBIR protocol meaning psoriasis patients under the age of 16 can enter the study. These patients will sign Assent with separate Parent/Guardian Consent provided to allow registration. As these participants reach the age of 16, it is requested new Consent is provided as per new adult recruits. As an observational study, all BADBIR participants are under the care of a dermatologist thus the updated consent will be obtained by the clinical or research teams locally. Patients will only be flagged with NHS Digital once the updated consent is in place (i.e. if only Assent and Parent/Guardian Consent, patient will not be flagged).

Publication of the results of analyses is ongoing. Results of the analyses are presented at relevant national and international scientific meetings, such as the British Association of Dermatologists, American Academy of Dermatology, International Conference on Pharmacoepidemiology (ICPE) and in peer reviewed journals e.g. British Journal of Dermatology (BJD), Journal of Investigative Dermatology (JID), JAMA Dermatology.

These will be targeted to ensure that the results are disseminated widely among the dermatology and the research community, including and the UK Dermatology Clinical Trials Network.

There has been a number of publications using BADBIR data in peer-reviewed journals to date. Most of these papers have also been presented at local, regional and international medical, nursing, scientific and patient conferences thus informing evidenced based clinical care. In addition, this “real world” experience of safety and effectiveness of these drugs will contribute to national guidelines of management of psoriasis e.g. NICE.

Studies with safety outcomes have recently been published including Risk of Major Cardiovascular Events in Patients With Psoriasis Receiving Biologic Therapies and an analysis of Risks of basal cell and squamous cell carcinoma in psoriasis patients. Both were published in the Journal of European Academy of Dermatology and Venereology in 2020 and 2021 respectively.

The up to date list of all publications arising from BADBIR data is posted on the BADBIR website (http://www.badbir.org)

It is expected that other papers will be published shortly including: incidence of suicide in the BABDIR population, rates of solid tumour in patients receiving biologic therapy compared to conventional systemic therapy and an investigation of the pathogenesis of paradoxical atopic eczema occurring in psoriasis patients on biologics. A research grant has been obtained from the Psoriasis Association which will explore the risks associated with switching between originator and biosimilar medications amongst other outcomes. It is anticipated that this analysis will be undertaken across 2021 and 2022.

All outputs will contain only data that is aggregated with small numbers suppressed in line with the HES Analysis Guide.

Six-monthly summary reports are provided to the BADBIR Data Monitoring Committee to include crude unadjusted rates of specific events of interests. Should a safety signal be identified, then further analysis can be requested and in the event of a significant concern the wider dermatology community will be informed. In addition, this “real world” experience of safety and effectiveness of these drugs will contribute to national guidelines of management of psoriasis e.g. NICE and thereby to the clinical management of patients with psoriasis.

A yearly Participant (patient) Newsletter which includes a summary of any published paper is also provided via the BADBIR website and the recruiting dermatology centres. YouTube and Twitter have also been used to disseminate information on BADBIR including two presentations at the Psoriasis Association annual meetings.

Data dissemination is managed by a data writing group who are responsible to the BADBIR Steering Committee. This group comprises of dermatologists, research scientists, dermatology nurses and patients with psoriasis and guide the potential for output for disseminated data to provide a measurable benefit.

The BADBIR Steering Committee is comprised of representatives of the data controller and will therefore contribute to this responsibility.

Published data will help clinicians and patients make more informed decisions about psoriasis treatment options. The following paragraphs outline the overall published benefits of BADBIR to date (i.e. not solely attributeable to NHS Digital data). These publications have provided more confidence to prescribers in best use of new biologic medications for treatment of psoriasis. It is hoped NHS Digital data will contribute significantly to the data analysis of BADBIR and help strengthen this confidence further.

There have been three publications in high impact journals on drug effectiveness. One paper concerned the length of time patients typically stay on biologic treatments when received as treatment for psoriasis. Biologics in clinical practice have a good overall survival rate in psoriasis patients but decrease over time; ustekinumab had the highest first-course drug survival in biologic-naive patients, followed by adalimumab. A paper followed which looked at duration of treatment for patients prescribed a second biologic therapy for psoriasis. This found that 77% of patients who were switched to a second biologic continued on the new treatment for at least 12 months. This shows clearly that patients experiencing treatment failure with one biologic therapy can benefit from switching to another. The results of this study should support clinical decision making when choosing second-line biologic therapy for psoriasis patients.

In 2017 a publication was made on the risk of serious infections for patients with psoriasis being treated with biologics. The University of Manchester did not find a statistically significant higher relative risk of serious infections for etanercept, adalimumab and ustekinumab as compared to non-biologic therapies for patients with psoriasis (e.g. methotrexate, ciclosporin). There was no difference in the risk of serious infections between etanercept, adalimumab and ustekinumab. The risk of serious infection, therefore, should not be a primary concern for patients and clinicians when deciding between non-biologic systemic therapies or these three biologic therapies for psoriasis.

BADBIR is monitoring drug safety over time and will look at lots of outcomes including heart conditions and cancer. The study has therefore analysed data to provide reassurance to prescribers that the treatments are safe in these outcomes researched. Risk of Major Cardiovascular Events (MACE) is not increased in patients with Psoriasis receiving Biologic Therapies. Also, BADBIR research has indicated there is no enhanced risks of developing two types of skin cancer (a basal cell or squamous cell carcinoma) by being treated with a biologic vs a conventional psoriasis drug.

There are no direct benefits for participants in BADBIR but the publications that arise from the project will contribute to the knowledge on the long-term safety of these new treatments thus benefiting patients in the future.

The University of Manchester (UoM) requires Civil Registration Mortality data, Cancer Registration data, and Hospital Episode Statistics Admitted Patient Care data to fulfil British Association of Dermatologists Biologics & Immunomodulators Register (BADBIR) study’s aim of assessing the long term safety of new treatments for psoriasis. Linkage data ensures that the capture of Serious Adverse Events on the study population is maximised.

Data will be processed under GDPR Article 6 (1) (e) and Article 9 (2) (j). The University of Manchester is a data controller and also processes the data for this study. No other organisations process the data for this purpose.

BADBIR is funded by the British Association of Dermatologists (BAD) and based at the University of Manchester (UoM) since its inception in 2007. It is an observational study which seeks to address the previously described limitations by systematically and prospectively evaluating safety in large numbers of “real world” patients receiving new treatments for psoriasis over a prolonged period compared to a comparator/control cohort. This type of register is considered to be the current gold standard in evaluating long-term treatment safety. This is achieved by following consented, registered participants and collecting information on drug exposure and adverse events (AEs). Therefore a more reliable and valid picture of long-term safety can be provided to clinicians and patients.

The data subjects are patients with moderate-to-severe psoriasis starting on a systemic treatment (i.e. tablet or injection) for their disease. Depending on the type of treatment being received, patients consent to be registered to one of three study cohorts (biologic, small molecule or conventional therapy).

Psoriasis is a chronic disease and there is interest in the long-term safety outcomes of patients exposed to these new immunosuppressant therapies. As such, all participants continue to be observed even if therapy is stopped or changed.

The University of Manchester collects data on study participants from dermatology departments.. The three datasets (Mortality, Cancers and Hospital Episode Statistics) provided via NHS Digital provide comprise serious adverse event (SAE) information. This is of particular importance where participants are lost-to-follow-up or not attending dermatology reviews as scheduled. As the information received contributes to other (BADBIR) study data it is required to receive pseudonymised fields to appropriately link. Both medical history and prospective data are relevant for BADBIR’s safety assessment thus a range of years have been requested across the NHS Digital datasets.

Patients with psoriasis often require lifelong treatment, which may expose them to toxic and potentially fatal side-effects. Biologics and more recently, small molecule immunotherapies have been licensed for the treatment of moderate to severe psoriasis. Despite the rigorous evaluation of efficacy and safety of these interventions, the evidence is based primarily on randomised placebo-controlled trials (RCTs) that are powered to detect differences in efficacy rather than to identify rare side-effects, or modest increase in risk of a common co-morbidity such as cardiovascular disease. These RCTs tend to have short placebo-controlled periods of about 12 weeks and so may not detect side-effects related to long-term use. In addition, RCTs have exclusion criteria (such as co-morbidities relevant to psoriasis) that may limit the ability to generalise the results to clinical practice. These drugs offer considerable benefits in safety and quality of life for those with moderate to severe psoriasis but questions remain regarding long-term safety, safety in particular circumstances (e.g. pregnancy and childhood), optimal treatment sequence, relative drug survival, and the use of co-therapies).

In the UK, voluntary spontaneous adverse event (AE) reporting is undertaken via the “Yellow Card” System. However, whilst useful for identifying rare events, it is rarely complete and therefore provides only limited information concerning the frequency of adverse reactions or their causality. Other sources of post-marketing safety information such as open label extensions to clinical trials may be subject to limitations including; survival bias, lack of a comparator group and lack of follow up on patients who cycle through various therapies.

Since the study’s inception in 2007 the register has obtained informed patient consent of over 13,600 individuals and still continues to recruit roughly 1,000 participants per year. Participants were provided consent information which explains the sharing of identifiers with NHS Digital (under its predecessor name at the time) for the release of mortality and cancer data should they occur to the University of Manchester. In 2017, the study obtained s251 support for the release of HES data for those individuals who consented under version 1 to 4. Since 11/09/2017, any new participants will be consenting (under version 5 or later) to the release of mortality, cancer, and HES from NHS Digital.

Publication of the results of analyses is ongoing. Results of the analyses are presented at relevant national and international scientific meetings, such as the British Association of Dermatologists, American Academy of Dermatology, International Conference on Pharmacoepidemiology (ICPE) and in peer reviewed journals e.g. British Journal of Dermatology (BJD), Journal of Investigative Dermatology (JID), JAMA Dermatology.

These will be targeted to ensure that the results are disseminated widely among the dermatology and the research community, including and the UK Dermatology Clinical Trials Network.

There has been a number of publications using BADBIR data in peer-reviewed journals to date. Most of these papers have also been presented at local, regional and international medical, nursing, scientific and patient conferences thus informing evidenced based clinical care. In addition, this “real world” experience of safety and effectiveness of these drugs will contribute to national guidelines of management of psoriasis e.g. NICE

The up to date list of all publications arising from BADBIR data is posted on the BADBIR website (http://www.badbir.org)

It is expected that other papers will be published shortly including: incidence of suicide in the BABDIR population, risk of keratinocyte cancers in patients treated with biologic therapy and risk of MACE in patients treated with biologic therapy. A research grant has been obtained from the Psoriasis Association to explore the risk of solid tumour cancer in patients treated with biologic therapy. It is anticipated that this analysis will be undertaken in 2020. An up to date publication plan is available on the BADBIR website http://www.badbir.org

All outputs will contain only data that is aggregated with small numbers suppressed in line with the HES Analysis Guide.

Six-monthly summary reports are provided to the BADBIR Data Monitoring Committee to include crude unadjusted rates of specific events of interests. Should a safety signal be identified, then further analysis can be requested and in the event of a significant concern the wider dermatology community will be informed. In addition, this “real world” experience of safety and effectiveness of these drugs will contribute to national guidelines of management of psoriasis e.g. NICE and thereby to the clinical management of patients with psoriasis.

A yearly Participant (patient) Newsletter which includes a summary of any published paper is also provided via the BADBIR website and the recruiting dermatology centres. YouTube and Twitter have also been used to disseminate information on BADBIR including two presentations at the Psoriasis Association annual meetings.

Data dissemination is managed by a data writing group who are responsible to the BADBIR Steering Committee. This group comprises of dermatologists, research scientists, dermatology nurses and patients with psoriasis and guide the potential for output for disseminated data to provide a measurable benefit.

The BADBIR Steering Committee is comprised of representatives of the data controller and will therefore contribute to this responsibility.

Published data will help clinicians and patients make more informed decisions about psoriasis treatment options.

There have been three publications in high impact journals on drug effectiveness. One paper concerned drug survival of biologic treatments for psoriasis received as first-line therapy. Biologics in clinical practice have a good overall survival rate in psoriasis patients but decrease over time; ustekinumab had the highest first-course drug survival in biologic-naive patients, followed by adalimumab. A paper followed on second-line drug survival which wound that 77% of patients who were switched to a second biologic continued on the new treatment for at least 12 months. This shows clearly that patients experiencing treatment failure with one biologic therapy can benefit from switching to another. The results of this study should support clinical decision making when choosing second-line biologic therapy for psoriasis patients.

In 2017 a publication was made on the risk of serious infections for patients with psoriasis being treated with biologics. The University of Manchester did not find a statistically significant higher relative risk of serious infections for etanercept, adalimumab and ustekinumab as compared to non-biologic therapies for patients with psoriasis. There was no difference in the risk of serious infections between etanercept, adalimumab and ustekinumab. The risk of serious infection, therefore, should not be a primary concern for patients and clinicians when deciding between non-biologic systemic therapies or these three biologic therapies for psoriasis.

There are no direct benefits for participants in BADBIR but the publications that arise from the project will contribute to the knowledge on the long-term safety of these new treatments thus benefiting patients in the future.

The University of Manchester (UoM) requires Civil Registration Mortality data, Cancer Registration data, and Hospital Episode Statistics Admitted Patient Care data to fulfil British Association of Dermatologists Biologics & Immunomodulators Register (BADBIR) study’s aim of assessing the long term safety of new treatments for psoriasis. Linkage data ensures that the capture of Serious Adverse Events on the study population is maximised.

Data will be processed under GDPR Article 6 (1) (e) and Article 9 (2) (j). The University of Manchester is a data controller and also processes the data for this study. No other organisations process the data for this purpose.

BADBIR is funded by the British Association of Dermatologists (BAD) and based at the University of Manchester (UoM) since its inception in 2007. It is an observational study which seeks to address the previously described limitations by systematically and prospectively evaluating safety in large numbers of “real world” patients receiving new treatments for psoriasis over a prolonged period compared to a comparator/control cohort. This type of register is considered to be the current gold standard in evaluating long-term treatment safety. This is achieved by following consented, registered participants and collecting information on drug exposure and adverse events (AEs). Therefore a more reliable and valid picture of long-term safety can be provided to clinicians and patients.

The data subjects are patients with moderate-to-severe psoriasis starting on a systemic treatment (i.e. tablet or injection) for their disease. Depending on the type of treatment being received, patients consent to be registered to one of three study cohorts (biologic, small molecule or conventional therapy).

Psoriasis is a chronic disease and there is interest in the long-term safety outcomes of patients exposed to these new immunosuppressant therapies. As such, all participants continue to be observed even if therapy is stopped or changed.

The University of Manchester collects data on study participants from dermatology departments.. The three datasets (Mortality, Cancers and Hospital Episode Statistics) provided via NHS Digital provide comprise serious adverse event (SAE) information. This is of particular importance where participants are lost-to-follow-up or not attending dermatology reviews as scheduled. As the information received contributes to other (BADBIR) study data it is required to receive pseudonymised fields to appropriately link. Both medical history and prospective data are relevant for BADBIR’s safety assessment thus a range of years have been requested across the NHS Digital datasets.

Patients with psoriasis often require lifelong treatment, which may expose them to toxic and potentially fatal side-effects. Biologics and more recently, small molecule immunotherapies have been licensed for the treatment of moderate to severe psoriasis. Despite the rigorous evaluation of efficacy and safety of these interventions, the evidence is based primarily on randomised placebo-controlled trials (RCTs) that are powered to detect differences in efficacy rather than to identify rare side-effects, or modest increase in risk of a common co-morbidity such as cardiovascular disease. These RCTs tend to have short placebo-controlled periods of about 12 weeks and so may not detect side-effects related to long-term use. In addition, RCTs have exclusion criteria (such as co-morbidities relevant to psoriasis) that may limit the ability to generalise the results to clinical practice. These drugs offer considerable benefits in safety and quality of life for those with moderate to severe psoriasis but questions remain regarding long-term safety, safety in particular circumstances (e.g. pregnancy and childhood), optimal treatment sequence, relative drug survival, and the use of co-therapies).

In the UK, voluntary spontaneous adverse event (AE) reporting is undertaken via the “Yellow Card” System. However, whilst useful for identifying rare events, it is rarely complete and therefore provides only limited information concerning the frequency of adverse reactions or their causality. Other sources of post-marketing safety information such as open label extensions to clinical trials may be subject to limitations including; survival bias, lack of a comparator group and lack of follow up on patients who cycle through various therapies.

Since the study’s inception in 2007 the register has obtained informed patient consent of over 13,600 individuals and still continues to recruit roughly 1,000 participants per year. Participants were provided consent information which explains the sharing of identifiers with NHS Digital (under its predecessor name at the time) for the release of mortality and cancer data should they occur to the University of Manchester. In 2017, the study obtained s251 support for the release of HES data for those individuals who consented under version 1 to 4. Since 11/09/2017, any new participants will be consenting (under version 5 or later) to the release of mortality, cancer, and HES from NHS Digital.

Publication of the results of analyses is ongoing. Results of the analyses are presented at relevant national and international scientific meetings, such as the British Association of Dermatologists, American Academy of Dermatology, International Conference on Pharmacoepidemiology (ICPE) and in peer reviewed journals e.g. British Journal of Dermatology (BJD), Journal of Investigative Dermatology (JID), JAMA Dermatology.

These will be targeted to ensure that the results are disseminated widely among the dermatology and the research community, including and the UK Dermatology Clinical Trials Network.

There has been a number of publications using BADBIR data in peer-reviewed journals to date. Most of these papers have also been presented at local, regional and international medical, nursing, scientific and patient conferences thus informing evidenced based clinical care. In addition, this “real world” experience of safety and effectiveness of these drugs will contribute to national guidelines of management of psoriasis e.g. NICE

The up to date list of all publications arising from BADBIR data is posted on the BADBIR website (http://www.badbir.org)

It is expected that other papers will be published shortly including: incidence of suicide in the BABDIR population, risk of keratinocyte cancers in patients treated with biologic therapy and risk of MACE in patients treated with biologic therapy. A research grant has been obtained from the Psoriasis Association to explore the risk of solid tumour cancer in patients treated with biologic therapy. It is anticipated that this analysis will be undertaken in 2020. An up to date publication plan is available on the BADBIR website http://www.badbir.org

All outputs will contain only data that is aggregated with small numbers suppressed in line with the HES Analysis Guide.

Six-monthly summary reports are provided to the BADBIR Data Monitoring Committee to include crude unadjusted rates of specific events of interests. Should a safety signal be identified, then further analysis can be requested and in the event of a significant concern the wider dermatology community will be informed. In addition, this “real world” experience of safety and effectiveness of these drugs will contribute to national guidelines of management of psoriasis e.g. NICE and thereby to the clinical management of patients with psoriasis.

A yearly Participant (patient) Newsletter which includes a summary of any published paper is also provided via the BADBIR website and the recruiting dermatology centres. YouTube and Twitter have also been used to disseminate information on BADBIR including two presentations at the Psoriasis Association annual meetings.

Data dissemination is managed by a data writing group who are responsible to the BADBIR Steering Committee. This group comprises of dermatologists, research scientists, dermatology nurses and patients with psoriasis and guide the potential for output for disseminated data to provide a measurable benefit.

The BADBIR Steering Committee is comprised of representatives of the data controller and will therefore contribute to this responsibility.

Published data will help clinicians and patients make more informed decisions about psoriasis treatment options.

There have been three publications in high impact journals on drug effectiveness. One paper concerned drug survival of biologic treatments for psoriasis received as first-line therapy. Biologics in clinical practice have a good overall survival rate in psoriasis patients but decrease over time; ustekinumab had the highest first-course drug survival in biologic-naive patients, followed by adalimumab. A paper followed on second-line drug survival which wound that 77% of patients who were switched to a second biologic continued on the new treatment for at least 12 months. This shows clearly that patients experiencing treatment failure with one biologic therapy can benefit from switching to another. The results of this study should support clinical decision making when choosing second-line biologic therapy for psoriasis patients.

In 2017 a publication was made on the risk of serious infections for patients with psoriasis being treated with biologics. The University of Manchester did not find a statistically significant higher relative risk of serious infections for etanercept, adalimumab and ustekinumab as compared to non-biologic therapies for patients with psoriasis. There was no difference in the risk of serious infections between etanercept, adalimumab and ustekinumab. The risk of serious infection, therefore, should not be a primary concern for patients and clinicians when deciding between non-biologic systemic therapies or these three biologic therapies for psoriasis.

There are no direct benefits for participants in BADBIR but the publications that arise from the project will contribute to the knowledge on the long-term safety of these new treatments thus benefiting patients in the future.