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I was interested to read that Kanthi Kiran V.S. Varanasi wrote that
(s)he would do a chest Xray in screening volunteers because we do not
do them in the UK unless there is a medical reason. The exposure is
about 0.02 mSievert from modern equipment, which is a trivial level of
risk but we still do not normally do them where the volunteer has
nothing to gain from being in the study. At that level the risk is
less than a tenth of the annual risk of homicide in the UK or 1/2,500
of a cancer or 1/50 of being killed in a traffic accident. I’m raising
this partly because I am interested in the consensus for acceptable
exposures from C-14 mass balance or PD studies using isotopes. We are
doing a study where the total exposure is going to be about 4.8 mSv and
it has passed ethics and national safety committee scrutiny, probably
because people routinely take that kind of risk without even thinking
about it since that is still only about the same as a return flight
from London to Cape Town in a commercial jet. Apparently, some
countries like Japan and Germany will not give any isotopes whatsoever
to volunteers and now if Chest X-rays (from modern equipment) are
routine in other countries perhaps we should start to do them in the
UK.
Thanks
Andrew Sutton.
Andrew Sutton, MBBS, MD(London), FFA
Medical Director
Guildford Clinical Pharmacology Ltd.
Hascombe Ward, Royal Surrey County Hospital,
Guildford, Surrey GU2 7YXX, UK
Tel: +44 (0)1483 406886
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The following message was posted to: PharmPK
Andrew Sutton wrote about:
> chest Xray in screening volunteers
that
> the U.K. does not do them unless there is a medical reason. The
> exposure is
> about 0.02 mSievert from modern equipment, which is a trivial level of
> risk but we still do not normally do them where the volunteer has
> nothing to gain from being in the study. At that level the risk is
> less than a tenth of the annual risk of homicide in the UK or 1/2,500
> of a cancer or 1/50 of being killed in a traffic accident.
I strongly approve of the U.K. policy about not requiring x-rays unless
a
medical reason exists. Because airplane passengers fly at higher
altitudes,
where incident radiation is greater, another risk comparison available
is miles
of plane flight. Unfortunately, the mortality and morbidity risks of
x-ray
exposure appear to be approximately linear and nonthreshold at low
exposure
levels. In other words, risk is proportional to x-ray exposure. So,
you can
multiply the cited risk levels by the number of persons x-rayed to
estimate
population risk. Since a person essentially cannot gain admission to a
U.S.
hospital without a chest x-ray, unnecessary radiation exposure becomes
a major
cause of iatrogenic mortality and morbidity in the U.S.
Daniel M. Byrd III, Ph.D., D.A.B.T.
8370 Greensboro Drive
McLean, VA 22102-3500
(703)848-0100
byrdd.-a-.cox.net
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Dear all
My query is:
Is it necessary to do Chest X-ray of all the volunteers who participate
in bioequivalence studies, or in studies where the volunteers don't
gain much clinicallly from the study ? Is there a greater risk to the
patients due to exposure to X-rays.
We at our Clinical Pharmacology Unit do bioequivalence studies and
invariably do Chest X-rays of all the volunteers during screening
before their participation in the study. Please comment on this.
Regards
Tausif Ahmed
Ph.D. student,
Dept. of Pharmaceutical Medicine
Ranbaxy CPU, Majeedia hospital,
Hamdard University, New DeLhi
India
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The following message was posted to: PharmPK
Dear Tausif,
In my initial comments I was trying to raise the flag for doing
anything to
volunteers mainly on the basis of scientific balance of risk and not
just
because they appeared once in a GCP guideline. In the UK we do not do
chest
X-rays even though the risk is so extremely small that they probably
would
be harmless. However, Daniel Byrd then pointed out that the
indiscriminate
use of X-rays by hospital in the US is on such a wide scale that even
these
small risks accumulate to serious iatrogenic injury across the nation.
In your case there could be a good reason for doing x-rays in all
subjects
and that is the relatively high incidence of tuberculosis. You may need
to
exclude TB patients not just because you will be expected to detect it
as a
normal part of medical care, but also to prevent cross infection to
other
volunteers and your staff. In that case I suppose you should be
avoiding the
risk of infecting even one subject, which would mean you would "err on
the
side of caution"
A parallel is doing HIV and Hepatitis blood tests, which we actually do
routinely in all subjects because there is a significant risk of
recruiting
an HIV +ve subject and at least a perceived risk of passing on the
infection
to nursing and laboratory staff.
I hope that helps...
Andrew Sutton
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Dear Andrew and Tausif
I fully agree with Andrew. Personally I am strictly against carrying
out Xray unless it is warranted. And if it is waranted you need to
exclude the subject in BA/BE trials, period. A neat and thorough
physical examination combined with a properly conducted biochem and
hemat lab examination will certainly helps you predict about health of
a subject. I was fortunate to implement this practice in a new startup
CRO few years back.
As far as spreading infection to others is concerned - the probability
is no different (thinking logically) than it is outside CPU. And no
matter how indepth examinations are, the normality of volunteers health
can never be assured 100%.
Thanks and regards
Dr.Prashant
Ph.D.
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Dear Andrew and Prashant,
I do agree with u to not to carry an unnecessary tests with the
volunteers and try to optimize the examinations to get fully healthy
status of the volunteers. But I found several times the volunteer are
having pulmonary koch's even though they were found all normal
parameters w.r.t urine, hematology, biochemistry and physical
examinations. Unfortunately in India no volunteer tells exactly about
his habbit and health history so it is always advisable to do all the
tests applicable. At the same time in India there are hardly any chances
of doing studies utilizing radio isotopes so there is no point of x-ray
effect.
However the radiation exposure in a chest x-ray is minimized by the type
of x-ray high-speed film, which does not require as much radiation
exposure as in the past.
I hope this helps.
KANTHI KIRAN V.S. VARANASI
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Dear All PK users,
I am not a medical person but reading about all the discussions about
the X-Ray and performing haemotological/biochemical tests, I would like
to ask: would not taking the X-ray/ performing these testsat the
initial stages in qualifing the subject as suitable for the study help
us later in case of any adverse event which the subject may report in
identifying the cause and its relation to the drug product if any.
Looking for veiws from the group,
Thanks
Naveen Sharma,
APL- Research Centre
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Dear Naveen,
I believe the answer to your question begins with analysing exactly why
the chest X-ray is being done. That means listing the possible
pathological conditions against which an X-ray would be an effective
guard and comparing them with the disadvantages of cost, volunteer and
department time as well as exposure to radiation. Theses disadvantages
would apply on a huge scale if every volunteer should undergo an X-ray.
There are not many conditions that could apply when you consider that
most chest pathologies would be detected by the medical examination and
other tests done in screening. You might suggest a lung cancer that
only becomes clinically evident 3 months after a study, but in fact the
diagnosis is most unlikely to be made on the pre-trial X-ray without
clinical symptoms. It would have to be an extremely rare tumour that
was big enough to be visible yet not causing any symptoms or clinical
signs such as coughing up small amounts of blood. Accordingly, the
X-ray is most unlikely to stop the volunteer enrolling even if the
tumour is just visible with hindsight when the diagnosis emerges 3
months after the trial. It would have the value of showing that the
tumour pre-dated the study drug but on the other hand, everyone knows
that this scenario will happen one day by chance if enough trials are
done, so why would anyone be surprised if it does occur? No logical
person would rush to blame the drug. However, we certainly would take
note and check other subjects who had taken the drug to find out if the
pattern were repeated. The likelihood of this occurring is so
vanishingly small that it is not worth attempting to detect it when you
compare it with the disadvantages of X-raying every subject. I guess
that hospitals in the USA do them routinely because a). They perceive
the risk of missing TB or a tumour as significant and b). it would be
so expensive in terms of legal damages if a staff member contracted TB
for example.
Another angle is the poor definition that X-rays achieve compared with
an MRI scan. The superb detail of an MRI might show the diagnosis
somewhat better..but the cost would be enormous and not a wise use of a
scarce resource in this day and age at least. In other words cost and
resource do play a role in determining what is accepted as normal
practice.
Another scenario is previously unsuspected congenital anomalies shown
in the pre-trial Xray. Here the anomaly would be known as such and
therefore could not caused by the study drug.
The one area where I think the X-ray could be an effective guard would
be in acute or subacute infections of the lung that show up on X-rays
and don't produce symptoms or obvious clinical signs. That effectively
means TB and some rare cyst producing infections not known in the UK
but might be a significant risk elsewhere. As far as TB goes I would
guess that Mantoux or other antibody testing would be a be more
reliable than X-rays, which only visualise the lungs and not the other
tissues where TB commonly lurks. From that I conclude that even where
TB is common it would be better to use a specific marker than a
non-specific chest X-ray. That is exactly the approach we take for HIV
and hepatitis.
I’d better not ramble on too long...
Kind regards
Andrew
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