Book 4: Guidelines

All MRC-supported medical research involving the use of ionising radiation and radioactive nuclides should be subject to the following general guidelines:

1. The irradiation of participants should be undertaken only by properly qualified and trained persons.
2. Irradiation should have the approval of the institution's Research Ethics Committee.
3. Approval should be based on the advice of an appropriate expert committee, and be subject to local and national regulations.
4. Volunteer participants should fully exercise their free will and sign forms granting their informed consent.
5. The estimated irradiation risks should be explained to subjects.
6. The magnitude of the risk to the volunteers should be authorised for each research programme.
7. Calculations of absorbed dose must be made, if necessary with the assistance of experts in the field, and the results, with some indication of the methods used, should accompany any submission to an Ethics Committee.

Users of radioactive sources must familiarise themselves with the characteristics of the radiation sources they use, whether alpha, beta or gamma emitters, for instance, and the specific precautions necessary in the use of these sources. It is permissible for radiation workers to be exposed to higher doses of radiation than the general public, at present 1mSv per annum, but the ALARA principle (as low as reasonably achievable) in terms of dosage and exposure should be observed. Radiation workers must ensure that they or their institution are registered with the Department of Health for work with the source they wish to utilise. They should be properly trained and informed concerning use of that source. The maximum permissible dose for radiation workers is 20mSv per annum.

8.1 General
All appropriate experimental tests, whether in vitro or animal, should be carried out and assessed before commencing on research involving the exposure of humans. In all instances the doses received by the subjects should be kept to the minimum consistent with obtaining the desired information or therapeutic benefit. The guidelines on doses given hereafter are applicable to an entire project; that is, a complete scheme of research designed to achieve a particular objective.

8.2 Selection of volunteers
Because of the possibility of ionising radiation producing long-term deleterious genetic effects, human volunteers, wherever practicable, should be older than 40 and preferably over 50 years of age. Paediatric participants may be at greater risk than adults of suffering deleterious effects after receiving ionising radiation. Therefore, except in the most exceptional circumstances, children should not be used as normal controls in research involving ionising radiation. However, where it is proposed that normal paediatric participants be irradiated, it is essential that such proposals be reviewed by several Ethical Committees, preferably located in different countries.

The number of volunteers participating in a project should be kept to the minimum necessary to obtain the required information with sufficiently small statistical uncertainty as accurately as possible, particularly when volunteers of reproductive age are used. Pregnant volunteers should be used only when problems specific to pregnancy are investigated. In these cases special consideration should be given to the embryo or fetus, with an estimate of its absorbed radiation dose and age at the time of administering the radioactive substances. The possibility of pregnancy occurring during the course of such research should always be borne in mind. Volunteers under the age of 18 years should be considered only in exceptional circumstances and when problems specific to their age are investigated.

8.3 Categories of research projects
Research projects should be classified according to the categories given hereafter. The distinction between categories is related to the total effective dose received by a research participant during 1 year. Examples should be provided of the types of benefits associated with research performed on persons in each of these categories.

8.3.1 Category I
The maximum permissible dose received by a research participant should not exceed 0,5 mSv which is the effective dose received as a result of natural background radiation, and is less than the effective dose received annually from this source of exposure.

8.3.2 Category II
The annual effective dose received by a subject may be greater than 0,5 mSv but less than 5 mSv. Thus the effective dose received will generally be of the order of that received as a result of natural background radiation.

8.3.3 Category III
The annual effective dose received by a subject may be greater than 5 mSv but less than 20 mSv. The effective dose received will generally be of the order of that permissible for occupational exposure.

8.3.4 Category IV
The annual effective dose received by a research participant may be greater than 20 mSv but less than 500 mSv. Research projects in this category should be permitted only in special circumstances. It would have to be convincingly demonstrated that the information required was important enough to justify the risks involved and that this information could not be obtained at lower dose levels.

8.4 Exposure of single organs
When organs or tissues are selectively irradiated, as is usually the case with research using radiopharmaceuticals and radiological examinations, higher doses to those organs and tissues may be permitted, with an overriding annual limit of 500 mSv for any single organ or tissue type. Calculation of the doses should be in accordance with factors given by the ICRP or other international regulatory and advisory bodies. Absorbed radiation doses to non-target regions must also be estimated.

8.5 Research proposals
A research proposal involving the exposure of human volunteers to ionising radiation should include a detailed statement of the aims of the study; a full motivation of the need for the study; quantitative details of the radiation dosimetry; the source and nature of the radiation and the number and particulars of persons to be exposed. Dosimetric considerations should include absorbed radiation by non-target tissues, organs and systems, which almost inevitably occurs.

The research proposal should also include the nuclides to be used; their physical half- lives and the nature of the emitted radiation; as much information as is available on their likely distribution due to metabolism and translocation processes in significant organs and tissues; the biological half-lives of the radionuclides and radiopharmaceuticals as well as any daughter products. The statement should also specify the chemical form in which the radionuclide will be administered; details of the vehicle for administration and of any residual contamination, and information on the acute or possible latent toxicity of the chemical agent or vehicle. In respect of radiological examinations, this information should include the techniques and equipment to be used; the region of the body to be exposed and projections required; the number of exposures and/or screening time and the proposed technique factors, including field sizes. The proposal should also specify techniques, if any, for:

1. the reduction of the doses received by tissues in the region of the body under examination, to the minimum compatible with obtaining the necessary information;
2. the delivery to the treated region of the body of a therapeutic dose of a magnitude that is most likely to ensure the required response;
3. the limitation, as far as practicable, of the exposure of other parts of the body.

Dose estimates giving the maximum level of dose and its location should be provided, together with an assessment of the dosimetry by an independent expert such as a medical physicist. Furthermore, the provisions for radiation protection measures to the subject and all others who are associated with the radioactive material, whether actively or passively, and any other relevant aspects, should be fully described. Exposure should be limited to the maximum permissible dose as described by the International Committee of Radiation Protection. The means for preventing administration of a dose greater than the permissible maximum must be described.

Worker Safety
The institution must take steps to ensure application of the ALARA principle in terms of exposure to workers. The maximum permissible dosage for workers is higher than that permitted for the public and may also vary for different categories of personnel, such as radiologist or laboratory worker. In general, safety is related to spatial and temporal separation from radiation source, and may include physical and mechanical barriers.

8.6 Authorisation
In addition to the requirement that such irradiation should be given only with the consent of the authorities in charge of the institution where it is to take place, as advised by an appropriate expert body, the use of ionising radiation is subject to national regulations and prior authorisation from the Department of Health.

8.7 Radioactive waste disposal
Investigators have an ethical and legal obligation to ensure that legislated protocols for waste disposal are carried out as prescribed.14 Institutions also have a duty to ensure that all appropriate protective and waste-disposal measures are meticulously carried out.