MR241 - GROWTH HORMONE THERAPY

This Data Sharing Agreement permits the retention of the data provided under previous iterations of this Agreement for an interim period. This is a pragmatic approach to provide an active Agreement whilst enabling Great Ormond Street Hospital for Children NHS Foundation Trust to complete the necessary actions to enable a subsequent application to extend the Agreement meeting all applicable data sharing standards as published in NHS Digital’s website (see: https://digital.nhs.uk/services/data-access-request-service-dars/dars-guidance).

The following provides background information on the purpose of the original study:

Background

The Department of Health and Social Care requires mortality and cancer data for the purpose of a project studying Creutzfeldt-Jakob Disease (CJD). It is important to continue this study until all the individuals have died. This is anticipated to carry on for several decades more.

It is important for public health and scientific reasons to maintain details of the life-status and incidence of CJD in these individuals treated with pritunary growth hormone.

Creutzfeldt-Jakob Disease (CJD) is a fatal brain disease for which there is no curative treatment. It occurs sporadically in the population, and can also be inherited in rare instances. It can be transmitted from an affected person to others by means of body tissues and fluids. Pituitary derived human growth hormone (pit-hGH) was extracted from dead people and used to treat short stature in approximately 1800 children in the UK. Tragically, the hormone material was contaminated with the agent which causes CJD and about 80 people in the UK have died as a result. The remainder are viewed as at risk of developing CJD. The aim and purpose of this agreement with NHS Digital is to collate death and morbidity data relating to this cohort of UK individuals treated between 1959 and 1985 with pituitary derived human growth hormone (pit-hGH). The data collected will enable appropriate public health intervention where risk to individuals treated may become apparent and also protect the public from the potential of a fatal transmissible illness.

The live treated individuals represent a public health risk as they could transmit CJD through organ donation or blood transfusion. For this reason the Department of Health (DHSC) need to be aware of the number of live individuals who carry this risk. PHE receives summary data to incorporate into a broader report in the form of a populated table, PHE do not further process summary data.

The DHSC funds an ongoing research study referred to as Growth Hormone Therapy in order to obtain summary statistics about this cohort of around 1800 patients who were treated in relation to CJD and possible increased risk of cancer.

The identity of the individuals treated with pit-HGH is known to the Growth Hormone Study and the data requested will enable ongoing surveillance of those still alive to monitor causes of death and morbidity potentially associated with the treatment in order to alert the cohort as appropriate. Risk of transmissible diseases to the public can also be identified.

As Department of Health and Social Care, in its capacity as an academic institute is a Public authority, lawful processing falls under Article 6 (1)(e) of the GDPR whereby “processing is necessary for the performance of a task carried out in the public interest or in the exercise of official authority vested in the controller.”

The data is also required for service evaluation purposes - meeting the conditions outlined as per Article 9 (2)(I) of the GDPR. Processing is necessary for reasons of public interest in the area of public health, such as protecting against serious cross-border threats to health or ensuring high standards of quality and safety of health care and of medicinal products or medical devices, on the basis of Union or Member State law which provides for suitable and specific measures to safeguard the rights and freedoms of the data subject, in particular professional secrecy.

The Department of Health has funded a longitudinal cohort study of people who received pit-hGH since 1988 when the risk of the development of CJD was first recognised as a risk factor in this population. The study has continued year on year as cases of CJD have continued to be identified and the risk of transmissible disease from this cohort of patients was identified. A potential increased risk of cancer has also been recognised in these patients and preliminary data may suggest a possible link with Alzheimers Disease or other brain disease. Data has been provided to support the study since it began and, where appropriate has been used to inform Public Health issues relating to possible transmission of disease.

The data supplied to Public Health England and the Department of Health and Social Care is aggregated, with no patient identifiable details. The applicant supplies the numbers of individual alive and dead, the number of cases of CJD and a histogram of the ages of the live individuals.

The purpose of the project is firstly to assess the public health risk of transmission of spongiform encephalopathies from this cohort of patients and secondly to identify deaths from CJD which could be secondary to pit-hGH by identifying cases of CJD that would not otherwise come to the attention of the research team. Thirdly the data to be collected about cancer registrations and deaths will assess whether there is an excess of malignancy compared with expected rates in the non-treated population.

The data required is:

Names – to ensure correct identification

DOB - to ensure correct identification

NHS numbers - to ensure correct identification

Last address known to the study team – from when it is arranged for patients to be informed of risk

Last GP known to the study team - from when it is arranged for patients to be informed of risk

Where in UK treated – historical data enabling contact with relevant local specialists

Treatment dates and hGH treatment batch numbers – to assess risk and study epidemiological factors; to inform the compensation process

Previous diagnoses – historical and for assessment of co-morbidities

Notes of previous contact with primary care – to optimise patient care

Dates when informed of risk of CJD – medicolegal; to ensure that patients can be advised accurately if they make contact.

These data will enable the data processor to know which patients are alive and to identify cause of death in those deceased. Cases of CJD that the research project was not aware of in life will be identified. Aggregate data related to the individuals, without any clinical or patient identifiable details are supplied biannually to Public Health England and Department of Health and Social Care to inform assessment of any public health risk from this cohort in a similar way to other individuals in other cohorts who represent a risk to public health.

The data processor holds the identities of the individuals and will continue to do so for the foreseeable future as patients contact the Growth Hormone Therapy research study for information about their previous treatment. This study has CAG approval under Section 251 of the National Health Service Act 2006. The data provided by NHS Digital needs to be mapped to the individual patient so that important links can be identified between, for example, the type of pit-hGH treatment and the risk of CJD or the risk of cancer and the type of pit-hGH prescribed, as there were several types.

The study is planned to continue until all the patients have died. Most of the patients are in their 40s so the likely lifetime of the project is for further decades.

Geographical data is needed in case a life improving intervention becomes available, potential need for information to be provided for local transfusion services and implications in relation to resources required to manage cases of CJD.

The cause of death and Clinical Commissioning Group data requested from NHS Digital is not available from other sources.

The data controller and data processor is Department of Health and Social Care.

The organisations receiving aggregate, non-identifiable data are PHE and DHSC. The research project currently has no collaborations with other researchers. However if evidence of other neurological disorders or cancer diagnoses became apparent from the data provided then there may be collaboration with appropriate data but only aggregated data would be provided.

There are no funders/commissioners involved

Under this Agreement, the data may be securely stored but not otherwise processed. No new data will be provided by NHS Digital under this Agreement.

The study data, including data provided by NHS Digital under previous agreements, are currently held by Great Ormond Street Hospital for Children NHS Foundation Trust.

Great Ormond Street Hospital for Children NHS Foundation Trust The following provides background on the processing activities undertaken prior to this Agreement:

All organisations party to this agreement must comply with the Data Sharing Framework Contract requirements, including those regarding the use (and purposes of that use) by “Personnel” (as defined within the Data Sharing Framework Contract ie: employees, agents and contractors of the Data Recipient who may have access to that data).

Under a previous iteration of this Agreement, NHS Digital supplied mortality data from 1985 to March 2017.Identifiers supplied to NHS Digital to flag the cohort were NHS Number, date of birth and last known address, it is not expected any new individuals will be notified.

Under this agreement cancer diagnosis and cause of death in the cohort will be supplied and there is no planned flow of data from the Growth Hormone Therapy study.

Access to the data will be restricted to members of the research team employed by Great Ormond Street Hospital who are specifically assigned to work on this study. The data will be used exclusively for the purposes of the specified study and none of the patient identifiable data supplied by NHS digital to the data processor will be shared with others.

At the end of the study, the data will be safely held on a password protected and encrypted drive at Great Ormond Street Hospital, for further 5 years, and accessed only to answer questions arising from the publication and other publicity if required. This will be the subject of a new agreement with NHS Digital.

The data processor, lead for the study, maps the patient identifiable data to the individual records of the cohort. Only aggregated data is shared with other parties.

The data processor will enter the personal data received from NHS Digital relating to individuals into a secure database containing the personal information about the cohort. This data is required to track and ensure correct identification. Periodic analysis of the database provides aggregated anonymised outputs for PHE and DHSC, these reports are biannual, dated end of June to end of December each year. The regular NHS Digital updates are taken into the analysis each time.

The patients are already known and identified. No new patients will be identified.

The data processor is GOSH and is the only organisation with access to the data.

All data is stored secured on the GOSH computer network, password accessible to the data processor from within the hospital or using secure remote access.

This Agreement permits the secure retention of the data only and no other processing.

No new outputs will be produced under this Data Sharing Agreement.

The research team analyses the data on a three-monthly basis for trends in mortality and cancer registrations. A six monthly summary report of anonymised aggregated data is supplied for Public Health England including number of live patients and age bands and annual report to the DHSC summarising number of cases of CJD, number of patients alive and any trends in mortality or morbidity.

If the data appears to suggest an increase in for example deaths from haemorrhagic stroke there would be a case for advising the at risk patients and their primary care physicians of this, as lifestyle or pharmacological interventions might reduce the risk of events. However such action would need to be considered in a multidisciplinary fashion, assessing the individuals best interest.

If new risks are identified, there could be a wish to publish summary results in academic literature. This would be important if there are findings which indicate that the cohort is at risk of illnesses which might be prevented or ameliorated if awareness were to be raised. These include lifestyle changes, monitoring, medication.

Historically where trends have been identified, anonymised data has been shared with appropriate researchers and led to publications.

Aggregate anonymised data with small numbers suppressed will be contained in all outputs.

This Agreement permits the secure retention of the data only and no other processing.

The CJD Unit can collate this unique data on incidence of hGH related CJD, relate this to treatment, and improve the advice given to professionals and the patients themselves, who make contact through the National Helpline.

It facilitates collaborate clinical correlations with illness details.

The individuals represent a public health risk by virtue of the transmissibility of the disease and are barred from the organ donation and blood transfusion. This cohort, and others such as those treated with contaminated Factor VIII, are the subject of national surveillance by Public Health England and the CJD Unit are the only source of information relating to the hGH recipients, updated with live data on death and cancer from NHS Digital/NHS Research/successor organisations.

The CJD Unit provide an expert national helpline for those concerned about treatment and CJD and co-ordinate the clinical care of those who develop CJD. The ability to do this is greatly enhanced by the unique current knowledge of numbers of cases. No other unit has details of the entire UK cohort.

The benefits are as follows:

• The identification of the size of risk to the general population of the risk of transmission of pit-hGH CJD

• The identification of any additional potentially transmissible diseases

• The identification of co-morbidities associated with pit-hGH and potentially prophylactic intervention

• Identification of any links between administration of particular types of pit-hGH and CJD and other co-morbidities

• Consideration of the underlying cause of growth hormone deficiency and pit-hGH treatment in relation to development of CJD and other co-morbidities

The formal outputs will quantify and disseminate to the Public Health England the risks outlined previously

Likely changes:

• Public Health England might reinforce advice to blood transfusion centres

• Public Health England might update and reinforce organ donation advice

• If a link with other transmissible diseases or co-morbidities is identified and treatment is available information can be provided to relevant health care professionals

• Public Health England and Primary Care Physicians would be responsible for the above

• Public Health England and Primary Care Physicians would be responsible for measuring any benefit

The holding of a national database of live individuals treated with hGH enables other health care professionals, such as infection control teams, to ascertain if an individual who may be in the at risk population actually received hGH. This is relevant in relation to blood donation services, organ donation services and individuals requiring surgical procedures for whom special precautions and equipment may be needed.

The continued surveillance this study has provided has shown that contrary to previously held views, the incubation period is in excess of 37 years and individuals are still at risk of CJD and presumably of transmitting it.