Request for data including addresses and ages to contact healthy controls for participation in STEC case-control study

The food poisoning bacteria Shiga-toxin E. coli (STEC) are a public health concern because of the severity of the infections caused. Evidence from outbreaks suggests that the transmission routes for STEC infection are evolving; for example, more outbreaks are now attributed to leafy vegetables as opposed to undercooked meat. Since a majority of infections in England are sporadic, case-control studies are the preferred method to determine risk factors for infections. However, the last case-control study on Shiga-toxin E. coli infections was performed in the late 90s; an update is urgently needed to reflect current causes of infection in England so better prevention strategies can be developed.

The University of East Anglia (UEA) is leading a STEC case-control study, working with Public Health England. This study has been funded by the NIHR Health Protection Research Unit in Gastrointestinal Infections (HPRU GI) project grant. The overall aim of this award is to bring Universities together with Public Health England (PHE) to assist in protecting public health, with the HPRU GI branch exploring the causes and distribution of diarrheal disease in the population. This Unit also funds studies led by other universities. Therefore, UEA also have access, should they need it, to specialist advice from the other universities funded by the Unit. The other universities have no control over decisions regarding this study, and no access to data provided by NHS Digital. As UEA does not have a Patient and Public Involvement Group (PPI), the University of Liverpool allows UEA to use their PPI Group.

This agreement relates to the first part of this study only, which is led by PHE. For this purpose, PHE requires a list of 50,0001 randomly selected (by age bracket) individuals registered with a GP in England, along with their addresses and ages. This information provided by NHS Digital will serve as a database of potential healthy control participants for a case-control study investigating Shiga-toxin E. coli transmission pathways. PHE will send invitation letters and study information to those individuals provided by NHS Digital to seek their consent in participating in the study. For this purpose, only substantive employees of PHE will have access to the personally identifiable data provided by NHS Digital as they have the data security systems in place to deal with such data. No other organisation will have access to the personally identifiable data provided by NHS Digital.

As part of routine surveillance, PHE collects questionnaires on potential transmission routes from all confirmed cases of STEC in England and Wales. PHE will be providing a pseudonymised dataset of all STEC cases during the study period, ending March 31st 2019, to UEA. In order to determine which potential transmission routes are associated with acquiring STEC infections, then the questionnaires of cases need to be compared to questionnaires completed by healthy control participants. The database provided by NHS Digital to PHE will be used to recruit these control participants.

NHS Digital will provide the lead researcher at Public Health England with a database containing the names, ages, and addresses of 50,001 individuals, aged 0-70 years, that are resident in England and registered with a GP. This will be stored on password protected PHE computers and will only be accessed by the research team at PHE authorised to work on the case-control study. They will access the database to print out addresses on envelopes and include names on information packets to invite people to participate as controls in our study. PHE would then post out the questionnaires.

UEA will only process data provided by the individuals who have directly responded. They will not process any data provided by NHS Digital.

This agreement relates to the above part of the study only. However, in order to make clear the broader context for this, details of the study processing as a whole are described below.

If someone from the database decides to participate, they will sign a consent form for University of East Anglia (UEA) to hold their data as provided by the questionnaire. The invitation letter will ask them to ensure they can be considered a “healthy” participant by the design of the study. The questionnaire will also ask them to provide their age and post code again, so that no personal information is being passed from PHE to UEA. The completed questionnaires will be returned to UEA for entry into a database of control subjects for the eventual analysis of the study.

The case-control study will run for a period of a year, potentially collecting up to 1,000 cases if current trends for STEC infections are maintained. The study proposes to recruit 2 controls for every case, meaning PHE will need up to 2,000 controls. Recently, a similar case-control study was performed by the University of Liverpool investigating Campylobacter infections. Based on their response rate of 4% for control participants, PHE will need to be provided 50,001 names and addresses to ensure that UAE are able to recruit the 2,000 controls. PHE are age-frequency matching controls to cases, and the following numbers have been determined using data from STEC infections for the past 10 years.

RANGES # to request

0-4 10455

5-9 5373

10-19 6341

20-29 9487

30-49 9971

50-70 8374

This is a mass mail out approach to up to 50,001 individuals asking them to consent to take part in the study. PHE will need the name, age, and address of all individuals provided so that they can invite those that are within the range of cases and write to them with the invitation packet at their address. The case-control study is for all of England, so there is no way to geographically restrict data in this manner. Recruitment began in February 2019 and will continue until the required number of control cases are consented. During the study, however, data will be deleted when this is requested by responders, and the information of non-responders will be deleted if they have not responded after the second contact attempt. Furthermore, the data of individuals that respond after 2,000 questionnaires have been received will be deleted from the database.

The output from having received the database, and therefore for this agreement, will be PHE contacting potential control participants to invite them to participate in the case-control study.

For the analysis of the completed study (which goes beyond the remit of this agreement) all results will be reported at an aggregate level, with no reference to any individual data, as odds ratios for different risk factors associated with STEC infection.

Once analysis is completed, a summary of results for the general public will be produced. This will be sent to any control participants that indicated in their consent form that they would like to be informed of any results and it will also be published on the NIHR Health Protection Research Unit in Gastrointestinal Infections website (hprugi.nihr.ac.uk). A peer reviewed research article on the study will also be produced for publishing in an Epidemiology journal. The results will also be presented at conferences, such as the HPRU GI annual conference, Public Health England’s Applied Epidemiology conference and at the International symposium for Shiga-toxin E. coli infections. PHE hope to have a draft of the research article prepared within one year of completion of the study, so by March 2021.

The benefit of receiving the database is that PHE will be able to recruit participants and successfully undertake the case-control study so that the research team can identify the most common sources for STEC infections and use this information to try and reduce the number of infections that occur per year in England.

Recruitment began in February 2019. PHE have recruited over 250 controls for the study.