1. Richard Smart
St George Hospital, NSW
RPS8 – Five Years On

2. RPS8
 RPS8, The Code of Practice for the Exposure of
Humans to Ionizing Radiation for Research Purposes,
was published by ARPANSA in May 2005.
 It replaced a 1984 NHMRC publication.
 It was adopted immediately in NSW.
 Five years later it is appropriate to examine how it has
been implemented in practice and whether its
requirements have stood the test of time.

3. RPS8
 The Code specifies the responsibilities of the
researcher, the medical physicist assessing the
effective dose and undertaking the radiation risk
assessment, the Human Research Ethics Committee
(HREC) and the Responsible Person.

4. Responsibilities of the Researcher
 Selection of participants ‐ special consideration given
to
 Age (where practical over 40 years & preferably over 50
years)
 Pregnancy – exclusion
 Breast‐feeding
 The researcher must provide the research participant
with sufficient written information about the purpose,
methods, radiation dose, associated risks and any
discomforts of the radiation exposure to enable the
research participant to give informed consent.

5. Responsibilities of the Researcher
 He/she must obtain an independent assessment or
verification by a medical physicist of:
 The total effective dose and relevant organ doses for
those radiological procedures that are performed
specifically for the research protocol and which are
additional to those received as a part of the research
participant’s normal clinical management;
 whether these will exceed the dose constraints listed in
Table 1 of RPS8; and
 the risks associated with the radiation exposure in
accordance with Annex 1 of RPS8.

6. Responsibilities of the Medical
Physicist
 The medical physicist must:
 independently verify the total effective dose and organ
doses and radiation risk assessment which have been
provided by the researcher; or
 assess the expected total effective dose and organ doses
which will be received by the research participant as a
result of their participation in the research and the
corresponding radiation risks; and
 where the dose constraints are exceeded, obtain
verification of the dose assessment by a second medical
physicist who must be independent of the researcher.

7. Responsibilities of the Human
Research Ethics Committee
 should consider the balance between the likely benefits and
risks associated with any radiation exposure
 should pay particular attention to:
 the estimates of expected radiation doses and associated risks,
which must have been calculated or verified by a medical physicist;
 the dose estimates and radiation risk assessments and opinion of
an independent medical physicist where the dose constraints are
exceeded;
 the manner in which the radiation doses and risks are provided to
the research participants in the information sheet;
 the justification for the radiation exposure particularly if the
radiation dose exceeds the dose constraints

8. The Responsible Person
 The Responsible Person is responsible for establishing
systems that ensure the overall observance of this
Code and its implementation.
 For South Eastern Sydney and Illawarra Area Health
Service the Responsible Person is the Chief Executive.

10. Dose constraints
 A dose constraint for research participants 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 in addition to that
received as part of normal clinical management.
 Dose constraints apply to diagnostic investigations not radiation
therapy.
 The dose constraint applies to the sum, over the relevant period, of
doses received from external exposure and the 50‐year committed
dose (to age 70 years for children) from intakes over the same period.
 When all the research participants are within the following specified
age limits, the following total effective dose constraints apply:
 for adult 60 years or more – in any year – 8 mSv and
 for adult 70 years or more – in any year – 12 mSv.

13. Identification of radiological
procedures
 Researchers are required to submit an application even if they
state that all procedures are for Clinical Management

16. Review of Research Applications
2005‐2010 at St George Hospital
 A review has been undertaken of the 87 radiation
dosimetry and risk assessments undertaken at St
George Hospital, as of June 2010 (now 99).
 There was no additional radiation in 22% of the
protocols.
 In the remaining 68 protocols the additional effective
dose ranged from 0.003 mSv (extremity x‐rays) to 170
mSv (multiple CT scans and bone scans over 10 years)

17. Effective dose in 68 projects
1
10
100
1000
0.001 0.01 0.1 1 10 100 1000
Effective dose in mSv
NumberofsubjectsatSGH

18. Distribution of doses by risk
category
 Using the nomenclature of Annex 1 of RPS8, the
additional effective dose was
 minimal (<0.2 mSv) in 11 studies,
 very low (0.2 mSv  dose < 2 mSv) in 12 studies,
 low (2 mSv  dose < 20 mSv) in 24 studies, and
 moderate ( ≥ 20 mSv) in 19 studies.
 Two studies involved radiotherapy only for which an
estimate of the effective dose is inappropriate.

19. Clinical conditions being
investigated
cancer 35*
thromboembolism 11
cardiac 3
renal 3
arthritis 3
osteoporosis 2
stroke 2
surgery 3
morbid obesity 1
fall 1
Vit D deficiency 1
multiple sclerosis 1
HIV 1
ICU patients on respirator 1
* Life
expectancy
< 5y in 30

20. Studies in children
 Only 2 studies involved children.
 Both of these required a bone density measurement
(effective dose 0.004 mSv)
 One study on 196 children with vitamin D deficiency
at birth
 One study on 50 children to assess the incidence of
osteoporosis in children and adolescents with severe
physical disabilities and to relate this to the presence
of risk factors in this population.

21. Local hospital or multi‐centre trial?
St George
Hospital only
22%
Australian
multi-centre
15%
International
multi-centre
63%

22. Clinical Management or Specifically
for the Research Project?
 The forms are usually completed by the Study
Coordinator (often a nurse)
 Need to carefully review the protocol to ensure that
there are no studies missed by the Coordinator.
 “Oh. I hadn’t realised a MUGA study involved
radiation”
 CT scans every 6 weeks for the monitoring of therapy
– All clinical management or are some additional for
this protocol?
 Protocols often international, multi‐centre, so little or
no flexibility

23. Optimising the exposure – can be
difficult
 A Randomized, Double‐blind, Placebo‐Controlled, Multi‐Center
Phase 3 Study of xxxxx as Adjuvant Treatment for Women with
Early‐Stage Breast Cancer at High Risk of Recurrence
 Each subject to receive a baseline bone scan, CT of chest and
abdomen and mammography.
 These imaging procedures to be repeated annually for a period
of up to 10 years. Of these procedures, only the annual
mammography would be performed as part of the subject’s
routine clinical management.
 The researcher proposed using an annual chest X‐ray and
abdominal MRI, but this was rejected by the trial sponsor. The
trial had US FDA approval.

24. Statements of Risk
 The Patient Information Statement must contain
information about the risks associated with
participation in the research.
 As supplied these can be way out:
 The amount of radiation is approximately three times
higher than the normal annual radiation dose from
natural sources (sun, soil, food, water) to which a
person is exposed. (For a chest/abdo/pelvis CT, ED =
14 mSv)
 This equals the amount you receive during a chest X‐
ray (For a bi‐lateral venogram, ED = 0.5 mSv)

25. What has changed since 2005?
 National Statement on Ethical Conduct in Human Research
(2007) from the NHMRC
 Australian Code for Responsible Conduct of Research (2007)
 National Ethics Application Form (NEAF) (web‐based)
 In NSW:
 NSW Supplement to the National Statement of Ethical Conduct in
Human Research (includes Research Governance)
 Establishment of Lead HRECs
 Site Specific Assessments

27. Single ethical and scientific review
of multicentre research
 NSW Health established a policy under which all human research
conducted at multiple sites within the NSW Health will be ethically
and scientifically reviewed once only (single review).
 This means that human research projects that are to be conducted at
more than one site and within the jurisdiction of more than one NSW
Health HREC (multicentre research), must be submitted to an
accredited lead HREC for single review.
 Public health organisations are required to undertake a site‐specific
assessment (SSA) of each research project, to allow the PHO to
consider whether it has the capacity to conduct the research at that
site.
 The SSA will involve consideration of such matters as resources, staff,
and patient availability but does not constitute another ethics review.

28. Effect of introduction of Single‐
Site review
0
5
10
15
20
25
30
2005 2006 2007 2008 2009 2010
No.ofapplicationsreceived
Jan - Aug

29. HoMER (Harmonisation of Multi‐centre
Ethical Review)
 Currently there are over 250 Australian HRECs in public and
private organisations, hospitals and universities.
 In October 2006, the Australian Health Ministers’ Advisory
Council (AHMAC), agreed to implement a national system
enabling the recognition of a single scientific and ethical review
process within and across all Australian jurisdictions.
 In the 2007 Federal Budget, $5.6M was allocated to the
Harmonisation of Multi‐centre Ethical Review (HoMER) project
over a period of four years.
 Includes a Certification Scheme for HRECs.

30. So, has RPS8 stood the test of time?
 Generally YES
 Clarified that only radiation exposure additional to that
received as part of clinical management needs to be
considered
 Adoption of a 50 mSv dose constraint for participants
with a life‐expectancy of <5 years has been workable,
and a big step forward compared to the single
constraint of 5 mSv per year.
 Requirements incorporated into NEAF
 Site‐specific dose assessments are critical, even if the
scientific merit is assessed centrally.

31. Study Titles
 Normoglycaemia in Intensive Care ‐ Survival
using Glucose Algorithm Regulation

32. Study Titles
 Normoglycaemia in Intensive CarE ‐ Survival
Using Glucose Algorithm Regulation
 NICE SUGAR
 Trial of Preoperative Therapy for Gastric and
Esophagogastric Junction Adenocarcinoma.

33. Study Titles
 Normoglycaemia in Intensive CarE ‐ Survival
Using Glucose Algorithm Regulation
 NICE SUGAR
 Trial Of Preoperative therapy for Gastric and
Esophagogastric junction AdenocaRcinoma.
 TOP GEAR