Radiation, Research Involving

Radiation, Research Involving Use of radioactive materials

Radioactivity and radiation are natural phenomena to which all humans are continuously exposed. This includes traces of radioactive material in the earth’s crust, radioactive gases in the air that we breathe, natural radioactive potassium in the body from food and drink and cosmic rays from space. This is often referred to as ‘background radiation’.

Diagnostic medical procedures are the most likely source of additional radiation exposure. Radiation may be delivered by X-rays passing through the body during diagnostic radiological procedures. Alternatively, internal exposure may occur during ‘nuclear medicine’ procedures, which use injected or ingested radioactive materials, that is, radiopharmaceuticals, to measure or image metabolic processes.

At one extreme, very high levels of radiation dose have clearly defined adverse effects. At the other extreme, higher ‘background’ radiation levels in certain geographical sites, or relatively small increases above background levels of exposures to radiation, have no proven adverse effects and may possibly even be beneficial. This presents some difficulties for Human Research Ethics Committees (HRECs) in evaluating the relative risks and benefits of research protocols using radioactive materials or X-rays. Nevertheless, prudent practice dictates the use of conservative radiation risk estimates, which assume that the negative effects from radiation may increase in a ‘straight line’ with the increase in the level of radiation dose from the very lowest to highest levels, with no assumed threshold below which there is no adverse effect at all. This assumption is known as the ‘linear no-threshold hypothesis’.

The international radiation protection community has, over many years, developed and applied the ALARA principle in developing guidelines that balance the benefits of radiation exposures against possible risks. This principle states that human exposures to radiation should be ‘As Low As Reasonably Achievable, with economic and social considerations taken into account’. [Footnote 124]

Within the context of medical and research exposures, this is usually taken to mean that each individual should receive no more radiation than is necessary to obtain reliable information and that no more research participants should be irradiated than is necessary to answer a particular scientific question. It is also taken to mean that special steps should be taken to minimise radiation exposures to people with elevated risk of adverse effects from radiation based on pregnancy or youth.

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Measurement and regulation of radiation exposure

For each research protocol that includes exposure of research participants to radiation, the dose of radiation exposure should be calculated by an appropriate institutional or external radiation physicist/radiation safety officer.

Radiation dose should be expressed in the following SI unit: 1 milliSievert (mSv) effective dose. This unit takes into account the type, intensity and duration of radiation, the amount and type of body tissues irradiated and the different radiation sensitivity of the irradiated tissues. The average natural background dose rate in Australia is 2 mSv/year. Medical exposures contribute about another 0.50.7 mSv/year. The current recommended limit for occupational exposure in Australia is 20mSv effective dose per year averaged over five consecutive years. [Footnote 125]

The NHMRC has recommended dose constraints for adult volunteers in medical research of 5 mSv in one year, with a maximum cumulative effective dose of 10 mSv over five years. [Footnote 126] This places an obligation on researchers to develop mechanisms to ensure that participants who are close to these dose limits do not inadvertently exceed the five-year limit by entering subsequent research studies involving radiation. It is also recommended that in children the total cumulative effective dose to age 18 years be restricted to a total of 5 mSv. [Footnote 127] These recommended exposure limits do not include medical exposures that are considered likely to be medically beneficial to the patient, or to be part of good medical care.

In each State and Territory of Australia, the Radiation Safety Section of the departments of health regulates radiation exposure to the public. All States, except South Australia, legally require the Radiation Safety Section of the State Department of Health to review and approve any research protocol that proposes to deliver any quantity of ionising radiation to totally normal healthy volunteers before final approval can be granted by an HREC. In South Australia, prior approval of such protocols by the State is not required, although the Radiation Protection Branch must be notified within seven days of approval by an HREC. Furthermore, legally required radiation exposure limits in South Australia are significantly less for normal volunteers aged under 18 years (0.5 mSv) and under 2 years (0.1 mSv) than the upper limit permitted by NHMRC Guidelines. Ethics committees assessing research proposals involving exposure of participants to ionising radiation must follow the requirements of State and Territory legislation and the NHMRC Recommendations for Limiting Exposure to Ionising Radiation (1995). [Footnote 128] In addition, Radiation Safety authorities are available to consult on other matters as required, for example, research protocols for therapeutic applications of radiation.

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Risks of radiation

The likelihood of adverse effects associated with diagnostic medical radiation exposures is generally considered to be low, but any possible effects may not present until many years after the radiation exposure. The two adverse effects most commonly associated with radiation exposure are an increase in the incidence rates of certain cancers and genetic damage.

The risk of cancer at low radiation doses (less than 50 mSv) is not proven, but by extrapolation to low doses of those risks obtained from analysis of research participants exposed to high doses, a maximum lifetime risk of cancer can be estimated at 1/18,000 per 1 mSv effective dose (compared with a 25 per cent lifetime natural risk of death from cancer). Evidence for cancer induction by moderate doses of radiation is strongest for children and progressively weaker with advancing age at the time of exposure.

The risk of adverse effects can be reduced by choosing research participants for irradiation who are over the age of 50 or beyond childbearing age, where this would not compromise the scientific value of the study. Because of the greater radiation sensitivity of children, participants under 18 years of age should usually be excluded from research with irradiation unless the condition or process being studied is peculiar to people under the age of 18. In this situation, particular care is needed to ensure that the lowest radiation exposure needed to obtain the necessary results is used.

The human embryo is especially susceptible to damage from exposure to radiation, particularly between seven and 17 weeks of pregnancy. Therefore, pregnant, or even possibly pregnant, women should be excluded from protocols involving radiation exposure.

Research involving radiation could also pose risks to laboratory personnel, nursing staff, and, occasionally, relatives of research participants. This should be avoided by ensuring that all irradiations are supervised by individuals with appropriate radiation training and State radiation worker licensing.

Researchers should ensure that potential radiation risks during research are minimised and that participants receive only the amount of radiation necessary to obtain the desired information. Research protocols should be reviewed by experts with appropriate qualifications and training and, as already noted, the number of participants included in the study should not be significantly greater than that required to answer the scientific question.

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Consent

Researchers should ensure that potential research participants are clearly informed whenever participation in research studies involves exposure to radiation. Participants must be given sufficient information if they are to make a meaningful decision as to whether or not to participate. One problem with communicating associated risks of radiation to potential research participants is that the risks from small radiation doses are not totally proven or quantifiable, although estimated upper limits of risk are available by extrapolation from higher doses. A further problem is that mathematical expression of these risks may be difficult for most potential participants to comprehend.

Several ways of explaining the potential risks associated with exposure to radiation have been suggested, although none are totally satisfactory. One method involves comparing the proposed ‘research effective dose’ with the ‘natural background effective’ dose received each year, or with ‘occupational effective dose’ limits. Another method involves comparing the maximum estimated risk of death from the proposed radiation dose with that of more familiar activities such as air travel or cigarette smoking. The uncertainties surrounding these risk estimates should be made clear to potential participants.

It may be appropriate to express the assessment of risk in more than one way, in order to maximise the informed nature of consent. However, it is not recommended that research radiation exposure be compared to exposure from chest X-rays. While this comparison has the advantage of familiarity and acceptability, it suffers from the disadvantage that the actual exposure to radiation from a chest X-ray may vary tenfold. Researchers should ensure that potential research participants have access to expert advice to answer questions they may have about proposed radiation exposure.

Points to consider

What effective dose of radiation will the participant receive during the proposed study, and what effective dose of radiation have they received in other research studies over the previous five years? Does this comply with NHMRC requirements? Have the requirements of all relevant State and Territory legislation and the NHMRC Recommendations for Limiting Exposure to Ionising Radiation (1995) been met?

Have pregnant women and unnecessarily young participants been excluded?

Is the participant a healthy volunteer, or is she or he a patient with a medical condition that may benefit from diagnostic or therapeutic consequences of the radiation exposure?