Information for persons involved in the irradiation of human
participants for research purposes
1.
General
The risks from exposure to ionizing radiation must be considered for any projects
involving the irradiation of human participants, either from external sources (e.g.
diagnostic x-rays) or internally administered radionuclides, beyond the levels which
they would normally be expected to receive.
The South Australian Environment Protection Authority requires that each subject be
informed in writing of this radiation exposure and its possible effects. In addition, it is
necessary to forward details of all projects involving radiation to the Radiation
Protection Division of the South Australian Environment Protection Authority. The
details required, which must be forwarded in writing through the Ethics Committee, are
as follows (S.A. Ionizing Radiation Regulations 44 and 45):
(a)
Full details of the research to be undertaken.
(b)
The number and the age group of persons to be exposed to ionizing radiation in
the course of the research programme.
(c)
The extent of the radiation exposure to be received by each subject involved in
the research programme.
(d)
The possible benefits to the research programme to the Community.
(e)
The steps to be taken to monitor the levels of ionizing radiation to which the
participants will be exposed.
(f)
The precautions which will be taken to keep radiation exposure to a minimum.
The Ethics Committee has the authority to approve projects involving radiation doses
up to the ARPANSA recommended limits (ut infra ). Projects involving radiation doses
beyond these levels must be forwarded to the EPA of SA for approval.
2.
Responsibilities of the Researcher
Any administration of ionizing radiation to human participants, either via external
irradiation or internally administered radionuclides, for the purposes of diagnostic or
therapeutic research must be undertaken only after evaluation by the ethics
committee. The researcher must prepare a submission to the ethics committee in
accordance with its requirements, and should include the following information:
•
Full details of the research to be undertaken.
•
The reasons why it is necessary to expose participants to ionizing radiation
for the purpose of this research.
•
•
The number, age range and sex of the participants to be exposed.
An estimate of the radiation exposure (effective dose and relevant organ
dose) to be received by each participant. The researcher must obtain
advice from a health or medical physicist who is qualified to perform the
necessary dosimetric calculations, measurements and monitoring.
•
•
The possible benefits of this research to society.
The name of the person responsible for security and maintenance of the
radioactive material, apparatus, or facility.
•
The steps to be taken to monitor the levels of ionizing radiation to which the
participants will be exposed.
•
The precautions which will be taken to keep radiation exposure to a
minimum.
•
Details of information to be given to participants and the consent form to be
used.
The researcher has a responsibility to provide the participant with sufficient
information about the purpose, methods, the radiation dose, associated risks and any
discomforts of the research, and to inquire about, and where possible verify the
participant's past dose history before allowing him/her to participate in the research.
It is unacceptable for the same participant to participate repeatedly in this kind of
research and thereby exceed, over a period of time, the dose constraint given in Table
1 below. Participants who confirm that they have had previous research exposures but
whose dose history cannot be verified, should be excluded. If at any time the
participant wishes to withdraw consent to the investigation, he/she has a right to
terminate his/her participation. The researcher must make arrangements to
maintain/retain records of the participants' signed consent forms, radiation doses and
details of the research undertaken. These records must be retained for a period of
time specified by the relevant legislation.
3.
Responsibilities of the Ethics Committee
Research proposals must be assessed by the Ethics Committee to ensure an
independent and impartial opinion of the necessity for the investigation and the
balance between the likely benefits and risks involved. This is most important where
the irradiation is not likely to benefit the participant, and, in evaluating each research
project before approval, the Ethics Committee must consider the information submitted
by the researcher covering the matters listed above. Particular attention must be
given to:
•
The manner in which the project is to be explained to the participant and
the informed consent obtained.
•
The estimates of expected radiation doses, which should be verified by a
qualified health or medical physicist.
•
The measures to be taken during the project to assess the radiation doses
delivered, and to keep them to a minimum.
•
The arrangements for keeping records of the participants' doses.
•
The number of persons who may be exposed.
•
The purpose of the research.
•
The possible benefit of the research to the community.
•
The risk, if any, to the health of the community that may be caused by the
research.
•
The general objective (the ALARA principle) as specified in:
i.
Section 23 of the South Australian Radiation Protection and Control Act, 1982
ii.
Australian Radiation Protection and Nuclear Science Agency (ARPANSA)
Exposure of Humans to Ionizing Radiation for Research Purposes, Radiation
Protection Series Publication No. 8, 2005.
Comparisons with natural background radiation levels (2.4 millisieverts per annum)
and absolute risk levels (approximately 5% per sievert effective dose) may be used as
rough guides to place the risk in perspective. Risk/benefit considerations are discussed
in more detail below.
4.
Responsibilities of Participants
Irradiation of the participant wishing to participate in a research project should be
permitted only when the participant has had the nature of the proposed project
explained, fully understands its risks and likely benefits, and willingly participates by
signing the consent form.
The participant or his/her guardian has a responsibility to
retain records of participation in investigations with radiation doses received, and to
provide this dose history to the researcher before any further exposure for research
purposes. The participant has the right to terminate participation in the project at any
time.
5.
Selection of Participants
Unless there is a known medical benefit to the participant which outweighs the risk of
the radiation exposure, the researcher should ensure that the selection of participants
is conducted according to the following criteria and any additional requirements of the
Ethics Committee:
•
Age - Partly because of the possibility of genetic effects and partly because
of the long latent period associated with certain somatic effects of radiation,
the participants should, where practicable, be over 40 years of age, and
preferably over 50.
•
Number of Participants - The number of participants irradiated must be
restricted to the minimum necessary to acquire, with sufficient accuracy,
the information needed.
•
Exclusions - Children (those under the age of 18) and pregnant women
must be excluded except when problems specific to those groups are being
investigated. Research involving irradiation of those groups must only be
performed when the information sought cannot be obtained by other
means, and the risks are minimal. The possibility that a woman may be
pregnant must be considered with regard to the use of women of
reproductive age as participants.
•
Radiation Dose Constraints for participants - The radiation dose to
research participants must be kept to the minimum level practicable, and
the total effective dose to adults and children should conform with the dose
constraints recommended by the ARPANSA [3] as given in Table 1 .
Table 1
[3]
Recommended Dose Constraintsa for Participants In Medical Research
Participant Category
Dose Constraint b,c
Adult participants in biomedical research
in any year
5 mSv
Total effective dose
over 5 years
10 mSv
Total effective dose in adult with life expectancy less than 5
in any year
50 mSv
in any year
200 mSv
e
in any year
100 mSv
f
d
Total effective dose
years
Equivalent dose to the skin averaged over 1cm
2
Equivalent dose to any other organ or tissue
Children and foetuses exposed in biomedical research
Total effective dose to age 18
Subject to:
5 mSv

Effective dose from conception to birth; and
0.1 mSv

Effective dose in any year from birth to 18 years
0.5 mSv
Total equivalent dose to age 18 to any organ or tissue
100 mSv
Notes
1. A dose constraint for participants in medical research specifies a maximum dose
with which it should be possible to comply in normal circumstances, and it is
intended to apply to radiation which is additional to that received as part of normal
clinical management. The dose constraint may apply to participants who do not
themselves benefit from the exposure.
2. The dose constraint applies to the sum, over all the relevant period, of doses
received from external exposure and the 50-year committed dose (to age 70 years
for children) from intakes of radioactive substances over the same period.
3. Any proposal to exceed these values should be referred to the appropriate authority.
4. When all the research participants are within the following specified age limits, the
following total effective dose constraints apply:
5. for adults 60 years or more
6. for adults 70 years or more
in any year
in any year
8 mSv and
12 mSv
7. Derived from Table 3.1 of ICRP85 factor of 10 below the threshold of 2 mSv for
early transient erythema.
8.
Derived from Table 3.1 of ICRP85 – factor of 10 below the threshold of 1 mSv for
detectable lens opacity.
6.
Assessment of Risk/Benefit
To facilitate assessment, research projects are generally divided into categories
depending on the radiation dose (effective dose) to be received by the participant. The
level of risk, the basic criterion for the definition of categories can be estimated from
the effective dose. The risk refers to the total detriment from the radiation exposure:
namely the sum of the probability of fatal cancers, the weighted probability of nonfatal cancers and the probability over all succeeding generations of serious hereditary
disease resulting from the dose.
This risk estimate to the general population is
averaged over the full age distribution. For people aged 50 years or over, the risk is
considerably less, about 1/5 to 1/10 of that for younger adults. For children, the risk
is 2 or 3 times greater than that for adults.
The categories of risk and the
corresponding levels of benefit to society expected from the radiation exposure are
given in Table 2 below [7].
The risk categories, differing from one to the next by an order of magnitude of
effective dose, and associated information, are given below:
Category I (risk of the order of 1 in 1,000,000)
The dose range for this project category is less than 0.2 mSv which is the dose
delivered by natural background radiation in a few weeks.
It is considerably less
than the variations in annual dose from natural background to persons living in
different locations, and the risk level is considered minimal.
The level of benefit
needed as the basis for approval of research with doses in this category will be minor
and will include those investigations expected only to increase knowledge.
Category II
The dose range for this category includes the annual doses received by essentially all
radiation workers in the course of their employment and the annual doses received
by members of the public from the totality of naturally occurring sources to which
they are exposed, apart from some of the doses from radon where radon
contribution to the annual doses is somewhat higher.
Category IIa (risk less than 1 in 100,000) represents a very low level of risk.
The dose range of 0.2 2 mSv covers the allowable annual dose to the public from
controlled sources; nevertheless, an intermediate benefit will be required. To justify
risks in this category the benefit will probably be related to increases in knowledge
leading to health benefit.
Category IIb (risk less than 1 in 10,000) represents low level of risk. The dose
range of 2 20 mSv covers the annual doses received by most radiation workers in
the course of their employment, and most diagnostic procedures. To justify the risk a
moderate benefit will be needed.
The benefit will be more directly aimed at the
diagnosis, cure or prevention of disease.
Category III (risk greater than 1 in 1,000 )
The dose range for this category is tens of mSv or more which incorporates the
current annual dose limit for occupational exposure (20mSv). It covers the higher
part of the range of annual doses from natural background radiation (including
radon), a region in which remedial measures to reduce doses are usually
recommended.
To justify research involving doses or risks in this category, the
benefit will have to be substantial and usually directly related to the saving of life or
the prevention or mitigation of serious disease.
Table 2
Categories of risk and corresponding levels of benefit [7]
Level of Risk
Risk Category
Effective Dose
Range for adults
(in mSv)
Societal
Benefit
Expected
Minimal
(1 in 1,000,000 or less)
Category I
Less than 0.2
Minor
Category II
IIa
From 0.2 to 2
Intermediate
From 2 to 20
Moderate
Greater than 20*
Substantial
Very Low
(1 in 100,000 to
10,000)
IIb
Low
(1 in 1000
10,000)
to
1
Moderate
(1 in 1000 or more)
in
CategoryIII
Note:
Dose to be kept below deterministic thresholds except where therapeutic procedures
involving radiation are being investigated. [A deterministic effect is an effect caused
by radiation, such as skin erythema, which only manifests itself above some
threshold dose and whose severity is dependent on the dose received.]
7. Code of Practice for the Exposure of Humans to Ionizing Radiation for
Research Purposes (2005)
The new code of practice, Australian Radiation Protection and Nuclear Science Agency
(ARPANSA) Exposure of Humans to Ionizing Radiation for Research Purposes, Radiation
Protection Series Publication No. 8, 2005, outlines in more detail the requirements
which must be met for the purpose of research involving humans who are exposed to
ionizing radiation that is not part of their normal clinical management.
This information (ARPANSA publication No 8, the code of practice) may be down
loaded, free of charge, from the following web-site :
www.arpansa.gov.au/rps8.htm
A hard copy may be purchased from ARPANSA at the cost of $16.50 per copy
8. Additional Sources of Information

Alaszewski A and Horlick-Jones T.
How can doctors communicate information
about risk more effectively? British Medical Journal 2003; 327:728-731.

Australian Radiation Protection and Nuclear Safety Agency (ARPANSA)
2002. Recommendations for limiting exposure to ionizing radiation (1995), and
National Occupational Health and Safety Commission (NOHSC) 2002, National
standard for limiting occupational exposure to ionizing radiation, Radiation
Protection Series No. 1, republished 2002, ARPANSA, Yallambie.

Calman KC.
Cancer: science and society and the communication of risk.
British Medical Journal 1996; 313: 799-802.

European Commission, Radiation Protection 99 Guidance on Medical Exposures in
Medical and Biomedical Research, 1999.
http://europa.eu.int/comm/energy/nuclear/radioprotection/publications/
doc/099_en.pdf.

Gigerenzer G and Edwards A.
Simple tools for understanding risks: from
innumeracy to insight. British Medical Journal 2003; 327:741-744.

International Commission on Radiological Protection (ICRP), 1991 – ICRP
Publication 62.
Radiological Protection in Biomedical Research. Annals of the
ICRP Vol.22 No.3. Pergamon Press, Oxford.

International Commission on Radiological Protection (ICRP), 2000 ICRP
Publication 85. Avoidance of Radiation Injuries from Medical Interventional
Procedures. Annals of the ICRP Vol. 30 No. 2 Pergamon Press, Oxford.

National Health and Medical Research Council (NHMRC), 1999 National
Statement on Ethical Conduct in Research Involving Humans (Issued by The
National Health and Medical Research Council (NHMRC) in accordance with the
NHMRC Act 1992 (Cth).
http://nhmrc.gov.au/publications/synopses/e35syn. htm.

National Radiation Protection Board (NRPB), 1993 Estimates of late radiation
risks to the UK population. Documents of the NRPB 4(4).

Paling J.
Strategies to help patients understand risks.
British Medical Journal
2003; 327:745748.

Therapeutic Goods Administration (TGA), 2004 Access to unapproved
therapeutic goods – Clinical trials in Australia.
http://www.tga.gov.au/docs/pdf/unapproved/clintrials.pdf.

World Health Organization (WHO), 1977 Use of Ionising Radiation and
Radionuclides on Human Beings for Medical Research, Training and Non-Medical
Purposes. Technical Report Series 611. WHO, Geneva