Help - Preparing & submitting applications - Radiation - defining research exposures
Help
  • Using IRAS
  • Preparing & submitting applications
    • HRA and HCRW ApprovalHRA and HCRW Approval
    • NHS/HSC R&D PermissionsNHS/HSC R&D Permissions
    • Ethical review (REC)Ethical review (REC)
    • Confidentiality Advisory Group (CAG)Confidentiality Advisory Group (CAG)
    • ARSACARSAC
    • HMPPSHMPPS
    • MHRA MedicinesMHRA Medicines
    • Site specific informationSite specific information
    • MHRA DevicesMHRA Devices
    • Templates for supporting documentsTemplates for supporting documents
    • HR Good Practice Resource PackHR Good Practice Resource Pack
    • Radiation AssuranceRadiation Assurance
    • Radiation - defining research exposuresRadiation - defining research exposures
    • Radiation - MPE and CRE review proceduresRadiation - MPE and CRE review procedures
    • Pharmacy AssurancePharmacy Assurance
  • Maintaining your approvals
  • End of research
  • FAQs
  • Documentation
  • Reference
Radiation - defining research exposures

Ionising Radiation - defining research exposures



What is a research exposure



Ionising radiation exposures are considered to be ‘research exposures’ where both the following criteria are met:
  • The exposure is required as an integral part of, and for the purpose of, the research. This specifically includes:
    1. exposures undertaken prospectively to confirm the eligibility of potential participants in the study and/or to provide (qualitative or quantitative) data regarding disease status at baseline; and/or
    2. radiotherapy as part of a treatment strategy to which patients are assigned prospectively by the protocol, either as part of an experimental or control arm, and which will be evaluated by the study; and/or
    3. exposures undertaken at formal time points within the trial protocol schedule to assess disease status or response to treatment; and/or
    4. exposures where there are clear requirements as to how they should be conducted e.g. machinery to be used, imaging slice thickness; and/or
    5. image-guided procedures undertaken whilst the patient is enrolled in the study

  • Consent for the exposure is sought from potential participants as part of their consent to take part in the research (including screening for eligibility).

Exposures which meet these criteria are considered to be research exposures even where they would otherwise be part of normal clinical care for patients in the same population treated outside the research setting, and whether or not research participation will result in ‘additional’ exposure over and above routine care.

Back to the top



Where a project involves a research exposure



Where a project involves a research exposure, this should be acknowledged in the IRAS project filter page and Part B Section 3 of the application form should be completed.



Additional notes and clarification



The online consent tool contains guidance on providing information related to research exposures to participants.

Where a protocol requires diagnostic imaging and allows a choice of modalities according to local practice, if any of these modalities involves ionising radiation it is a research exposure (for example, MUGA as an alternative to echocardiogram, CT as an alternative to MRI).

In some cases, protocols may refer to other radiation exposures, which are administered as part of clinical care outside the study rather than as research exposures.

For example:
  • The selection criteria for a study may require a participant to have previously undergone a particular type of radiation exposure in order to be eligible for recruitment;
  • The protocol may expressly allow for radiotherapy to be given during the study, where this is not part of the study treatment (either experimental or control arm) and will not be studied separately within the analysis.
Such exposures are not research exposures provided that:
  • They are authorised in the course of normal clinical care, not for research purposes; and/or
  • The decision to authorise the exposures is clearly separated from the decision to include the participant in the research and is not determined prospectively by the research protocol; and/or
  • Consent for the exposure is not sought as part of the consent to take part in the research or to be screened for eligibility; and/or
  • The information obtained from the exposure is not used as data for the purposes of the study e.g. to provide (qualitative or quantitative) data regarding disease status.


Further advice



Where any doubt arises as to whether a procedure involves ionising radiation or is a research exposure for the purposes of IR(ME)R, researchers are advised to seek early advice from a Medical Physics Expert (MPE) in their organisation or one of the host organisations for the research. Further advice may be sought from the HRA Queries Line if necessary.

Sometimes it can be difficult to distinguish whether a radiation exposure is defined as a research exposure or not. The information in the section below "Defining research exposures - examples" sets out some guidelines to help identify a research exposure based on the principles listed above.

The tables provide various examples with comments on whether the radiation involvement would be defined as a research exposure, including additional advice on whether ARSAC involvement is required.



Defining research exposures - examples



This section gives a range of typical examples where questions could arise about whether the study involves a research exposure. The examples aim to illustrate how the above guidance should be interpreted in practice. Guidance is also given on the need for a Preliminary Research Assessment (PRA) application to the Administration of Radioactive Substances Advisory Committee (ARSAC). Please note that the list of examples is not exhaustive.
  1. Screening X-ray to determine eligibility for inclusion
  2. Complementary therapy in patients who have had radiotherapy
  3. Investigation of contrast media reactions in patients who have had CT imaging
  4. MRI study with X-ray to check for metallic objects
  5. Use of Glomerular Filtration Rate
  6. Oncology trial with follow-up imaging to assess study endpoints
  7. Follow-up imaging to be determined by local practice
  8. Protocol with option of MUGA or echocardiogram
  9. Phase I healthy volunteer trial using PET
  10. Physiology study using DXA
  11. Palliative radiotherapy
  12. Use of data from exposures authorised outside the study
  13. Clinical investigation of a novel medical device to be inserted using X-ray fluoroscopy
  14. Post-implant imaging to check the correct positioning of a novel device
  15. Post-market study of CE marked device previously inserted using X-ray fluoroscopy
  16. Comparing standard of care X-ray to an MRI
  17. Use of standard of care PET-CT scan to determine whether participants should remain in the trial or be removed
  18. CT scan performed prior to the research required as part of screening procedure or inclusion criteria to confirm size of tumour


1. Screening X-ray to determine eligibility for inclusion


Example


The eligibility criteria for a clinical trial in HIV infection specifically exclude patients with tuberculosis (TB). The protocol requires potential participants to undergo a chest X-ray to exclude TB prior to recruitment.


Research Exposure


Yes.


Rationale


The X-ray is part of the screening procedures and occurs after consent. The X-ray is required as an integral part of the protocol in order to inform decisions about study eligibility.


ARSAC PRA


No. The research exposure (X-ray) does not involve the administration of radioactive substances.


Additional comment


Consent for the research must be sought prior to the X-ray.



Back to the list of examples



2. Complementary therapy in patients who have had radiotherapy


Example


The study will compare the effectiveness of several complementary therapies in relieving the symptoms of treatment for breast cancer. The eligibility criteria specify that patients must be having radiotherapy as part of their treatment.


Research Exposure


No.


Rationale


Radiotherapy is authorised as part of normal clinical care outside the context of the study. It is not required as part of the research protocol.


ARSAC PRA


No. This research does not involve the administration of radioactive substances.


Additional comment


N/A



Back to the list of examples



3. Investigation of contrast media reactions in patients who have had CT imaging


Example


The study will investigate patient reactions following administration of different types of X-ray contrast media during CT examinations undertaken in the course of standard care.


Research Exposure


No.


Rationale


The CT scans are part of the eligibility criteria for the study and, although the data from the CT scans are collected for the purposes of the research, the CT scans are not required as part of the research itself. The protocol makes no specific requirements on the imaging exposure and the scans are authorised as part of normal clinical care outside the context of the study. It is assumed that the contrast media used in the study are not radioactive.


ARSAC PRA


No. This research does not involve the administration of radioactive substances.


Additional comment


The key point here is that the CT scan is not detailed in the protocol. Another example would be when X-rays are conducted at follow-up for standard of care, the data from these may be collected for the purposes of the research but the protocol does not specify any conditions on the data. The exposure itself is not part of the research or included in the protocol.



Back to the list of examples



4. MRI study with X-ray to check for metallic objects


Example


A clinical trial will use MRI scans to assess response to treatment. The standard screening for contraindications to MRI includes questions to check whether patients could have metallic foreign bodies present in biologically sensitive areas, for example as a result of a previous head injury. The protocol requires patients presenting with this possibility to be referred for X-ray.


Research Exposure


Yes


Rationale


The MRI scans are required by the protocol to assess the study endpoints and are an integral part of the research. If a patient requires an X-ray in order to take part in the study, this X-ray would be a research exposure.

The X-ray is a screening procedure, occurs after consent and is specified in the protocol.


ARSAC PRA


No. The research exposure does not involve the administration of radioactive substances.


Additional comment


Studies have found that the presence of metallic objects is extremely low in the general population. Therefore, unless the study targets a population in whom this is likely to be a feature (e.g. wounded military personnel), the simplest approach would be to exclude patients presenting with the need for X-ray. The study would not then involve ionising radiation exposure.



Back to the list of examples



5. Use of Glomerular Filtration Rate


Example


In a CTIMP the dose of the administered experimental drug X will be based on EDTA clearance measured by Glomerular Filtration Rate (GFR).


Research Exposure


Yes.


Rationale


Measuring GFR based on EDTA clearance includes the administration of a radionuclide. Measuring GFR in this manner is required by the protocol in order to deliver an appropriate dose of the study drug.


ARSAC PRA


Yes. The GFR includes the administration of a radionuclide.


Additional comment


GFR is often estimated by measuring creatinine clearance (e-GFR), which does not involve the use of ionising radiation and therefore is not a research exposure. It should be noted that the e-GFR and GFR determined by EDTA clearance are two different procedures, the latter of which may be a research exposure.



Back to the list of examples



6. Oncology trial with follow-up imaging to assess study endpoints


Example


A randomised controlled trial will assess the efficacy of a novel chemotherapy agent in comparison with the standard regime for patients with advanced ovarian cancer.

The protocol requires patients to have CT scans after 1 month, 3 months, 6 months and thereafter 6 monthly until disease progression in line with normal care at most sites.

A bone scan will be administered to check for metastatic disease prior to treatment and, if positive, this will be repeated at 6 monthly intervals.


Research Exposure


Yes.


Rationale


The initial bone scan and any follow-up scans are research exposures.

Even though the follow-up CT scans would be normal care outside of the study, they would be classed as research exposure as they are needed to assess the endpoints of the study and are an integral part of the protocol.

The research protocol gives clear information as to how the exposures should be conducted. It specifies the frequency, administration, method, processing or clinical evaluation of the exposures, including specifications of machinery to be used.


ARSAC PRA


Yes - the bone scan is a nuclear medicine procedure (i.e. involving the administration of radioactive substances).


Additional comment


N/A



Back to the list of examples



7. Follow-up imaging to be determined by local practice


Example


A Phase III clinical trial states that follow-up imaging of the disease should be conducted 'as per local clinical practice'. It is unclear from the protocol how the results of the imaging will inform the study.


Research Exposure


Yes.


Rationale


Radiation exposures are required by the protocol, though they are ill-defined.


ARSAC PRA


Unclear. An application would be required if any of the scans involve nuclear medicine (i.e. the administration of radioactive substances).


Additional comment


This is an example of a poorly written protocol. It is unclear from the protocol how the results of the imaging will inform the study. It is important that only those exposures required to assess the endpoints for the study are specified in the protocol. Approval for the study is likely to be delayed while further clarification is sought.



Back to the list of examples



8. Protocol with option of MUGA or echocardiogram


Example


A study in coronary heart disease requires either a multi-gated acquisition (MUGA) scan or an echocardiogram (ECHO). Alternatively, a chemotherapy trial may require either a MUGA scan or an ECHO to be performed at set time points to monitor and/or assess impairment in cardiac function as a result of the chemotherapy, and this to decide whether treatment needs to be halted. The protocols allow sites to opt for either MUGA or ECHO according to local practice.


Research Exposure


Yes.


Rationale


Although the study could be conducted without ionising radiation exposure (i.e. without MUGA scan), the protocol includes an option to use MUGA in preference to ECHO and therefore it potentially involves ionising radiation at some sites.


ARSAC PRA


Yes - MUGA is a nuclear medicine procedure requiring the administration of radioactive substances.


Additional comment


N/A



Back to the list of examples



9. Phase I healthy volunteer trial using PET in a single-site study


Example


A Phase I trial is being conducted to assess the safety and pharmacokinetics of a new agent in healthy volunteers. The research protocol requires PET scans.


Research Exposure


Yes.


Rationale


PET is required as part of the research protocol for the study and as healthy volunteers participants would not usually receive this exposure.


ARSAC PRA


Yes - PET is a nuclear medicine procedure requiring the administration of radioactive substances.


Additional comment


N/A



Back to the list of examples



10. Physiology study using DXA


Example


A physiology student is undertaking an MSc study of bone density, involving tests on healthy volunteers. The study requires dual energy X-ray absorptiometry (DXA) scans, which will be carried out in accordance with standard protocols in place at the university.


Research Exposure


Yes.


Rationale


Although exposure from a DXA scan is minimal, the study involves ionising radiation as an integral part of the research protocol. It specifies the frequency, administration, method, processing or clinical evaluation of the exposures, including specifications of machinery to be used.


ARSAC PRA


No. This research does not involve the adminstration of radioactive substances.


Additional comment


DXA scans are common in university research in disciplines such as physiology and sports science. Although the research involves healthy volunteers rather than NHS patients, REC favourable opinion of such research is a legal requirement under IR(ME)R.



Back to the list of examples



11. Palliative radiotherapy


Example


A clinical trial seeks to treat advanced cancer patients with a novel agent. Median survival is expected to be less than 12 months. The protocol mentions that, in addition to concomitant medications, palliative radiotherapy may be given to patients with bone metastases in line with clinical need and local practice. Giving radiotherapy will not affect the primary outcome of the study.


Research Exposure


No.


Rationale


Although the protocol mentions the possibility of radiotherapy being administered to patients in the study, the radiotherapy is not required by the study and will not affect the study outcomes. Patients receiving radiotherapy will not be studied as a separate arm of the design. Delivery of radiotherapy is entirely dependent on clinical need, not the requirements of the research. Consent to undergo radiotherapy is not sought as part of the consent to take part in the study.


ARSAC PRA


No. This research does not involve administration of radioactive substances.


Additional comment


If adjuvant radiotherapy was considered likely to affect the outcomes of the study and patients receiving radiotherapy were studied separately, it should then be considered a research exposure.

Any radiotherapy treatment will still need to comply with employers’ IR(ME)R procedures but not as a research exposure. It is not necessary for the REC to have an assessment of the potential exposure or to approve it as part of the ethical review.



Back to the list of examples



12. Use of data from exposures authorised outside the study


Example


The protocol for a clinical trial in myeloma states that results from a standard axial skeletal survey will be requested to inform the care of patients on a day-to-day basis while in the trial.


Research Exposure


No.


Rationale


An axial skeletal survey is recommended by national guidelines as part of the clinical diagnosis of myeloma. The axial skeletal survey will have been authorised in the course of normal clinical care outside the context of the trial. The results of the imaging are not required to assess the study endpoints.


ARSAC PRA


No. This research does not involve administration of radioactive substances.


Additional comment


Although the data from the axial skeletal survey are collected for the research, the protocol does not specify any conditions on the data and the data is not critical for the outcomes of the study.



Back to the list of examples



13. Clinical investigation of a novel medical device to be inserted using X-ray fluoroscopy


Example


A manufacturer-led clinical investigation for CE marking of a novel cardiac stent seeks to treat patients with coronary heart disease. Patients require X-ray guided insertion of the device as part of the Clinical Investigation Plan, and requirement for a stent is part of the inclusion criteria. Normal care outside the study would involve X-ray guided insertion of a standard stent.


Research Exposure


Yes.


Rationale


The X-ray is integral to the investigational procedure required, and will be authorised in the context of participation in the research rather than as part of normal clinical care. This position is not altered by the fact that the same procedure would be received outside the study by a patient opting not to take part. The research protocol specifies the frequency, administration, method, processing or clinical evaluation of the exposures, including specifications of machinery to be used.


ARSAC PRA


No – the X-ray is not a nuclear medicine procedure (i.e. requiring the administration of radioactive substances).


Additional comment


Although X-ray is used in standard care, there may be changes in the radiation dose delivered to study participants due to the novelty of the device requiring additional projections or imaging sequences. This should be addressed as part of the Lead MPE dose and risk assessment within IRAS.



Back to the list of examples



14. Post-implant imaging to check the correct positioning of a novel device


Example


A manufacturer-led clinical investigation seeks to obtain a CE mark for a novel hip implant. The Clinical Investigation Plan specifies the need for a post-implant X-ray to check the correct positioning of the device.


Research Exposure


Yes.


Rationale


The X-ray is required by the protocol for the study.


ARSAC PRA


No - the X-ray is not a nuclear medicine procedure (i.e. requiring the administration of radioactive substances).


Additional comment


N/A



Back to the list of examples



15. Post-market study of CE marked device previously inserted using X-ray fluoroscopy


Example


A manufacturer-led post-market study seeks to gain further data on the safety, performance and efficacy of a CE marked cardiac stent already established as standard treatment at participating centres. X-ray guided insertion of the stent is standard clinical practice.


Research Exposure


No.


Rationale


The X-ray is authorised as part of normal clinical care, not for the purpose of the research. Consent to undergo the exposure is not part of the consent to participate in the study.

The research protocol specifies that X-rays are conducted according to standard of care at site and the data from the X-ray is collected for the purposes of the research, but the protocol does not specify any conditions on the data.


ARSAC PRA


No. The research does not involve the administration of radioactive substances.


Additional comment


N/A



Back to the list of examples



16. Comparing standard of care X-ray to an MRI


Example


The inclusion criteria references participants having an X-ray as part of standard care; an MRI is performed at the same time as the X-ray and both procedures (MRI and X-ray) are being compared as part of the research.


Research Exposure


Yes.


Rationale


The X-ray is part of the inclusion criteria and is conducted after consent is gained. The X-ray, or data from the X-ray, is required for the research in order to compare the two scans.

The research protocol specifies the details of the X-ray, such as frequency, administration, method, processing or clinical evaluation of the exposure and specifications of machinery to be used


ARSAC PRA


No. This research does not involve the administration of radioactive substances.


Additional comment


The exposure may be conducted at any point in the study.



Back to the list of examples



17. Use of standard of care PET-CT scan to determine whether participants should remain in the trial or be removed


Example


Part way through the research, participants have a PET-CT scan related to the trial, if clinically indicated, to check for the presence of metastases. Participants will be removed from the study if metastases are discovered.


Research Exposure


Yes.


Rationale


The PET-CT scan is integral to the research and will be authorised in the context of participation in the research rather than as part of normal clinical care. This position is not altered if the same procedure would be received outside the study by a patient opting not to take part.

The research protocol specifies the frequency, administration, method, the processing or clinical evaluation of the exposure, including specifications of machinery to be used.


ARSAC PRA


Yes – PET is a nuclear medicine procedure requiring the administration of radioactive substances.


Additional comment


Alternatively, if participants required a PET-CT scan under local standard of care in response to symptoms unrelated to the trial, which could lead to their removal from the trial, the PET-CT scan would not be a research exposure because it was authorised as part of normal clinical care, not the research itself.



Back to the list of examples



18. CT scan performed prior to the research required as part of screening procedure or inclusion criteria to confirm size of tumour


Example


The inclusion criteria states that participants have been diagnosed with a tumour, confirmed by a CT scan.


Research Exposure


No.


Rationale


Whilst part of the screening procedures and referenced in the inclusion criteria, the CT scan occurs prior to consent.


ARSAC PRA


No.


Additional comment


Each participant’s medical records will be checked for the CT scan and diagnosis by the care team prior to the participant giving consent to take part in the study.



Back to the list of examples

Back to the top






Page last updated: 23 November 2018




 
IRAS Integrated Research Application System, version 5.13, 22/07/2019, IRAS Dataset version 3.5.
The Health Research Authority (HRA) acknowledges the Integrated Research Application System (IRAS) partners in developing IRAS content. © Health Research Authority 2019.
Copyright and other intellectual property rights in the content of the Integrated Research Application System (IRAS) belong to the HRA and all rights are reserved. Terms & Conditions, Privacy Policy.