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Letters to the Editor
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Drug trials
How can unfortunate events be prevented?
From Mr J. M. Fallon, MRPharmS
I write concerning the unfortunate outcome of the drug trial involving
TGN1412, a humanised monoclonal antibody, as a prospective drug treatment.
The inference gleaned from the reported crisis is that two critical factors
were involved:
· It seems as though all volunteers who received the substance did
so within a finite time period before the drastic adverse reactions suffered
· A defined bolus/amount was administered; predetermined, presumed
safe to elicit an effect of interest to meet regulatory requirements
It is an unfortunate, thankfully rare incident happening at the dawn of
a new era in medicine, with the progressive use of biologically derived
active substances. As such, the implications for conducting trials of these
substances will undoubtedly become more stringent than those resulting
from the “anatomy of disaster” that was the thalidomide debacle
of the 1960s, and to which all subsequent trials are subjected. I am not
suggesting for a moment that the companies involved were careless or unethical
in their approach. Nor am I critical of the healthy volunteers or attributing
a cavalier attitude to how they conduct their lives. Far from it. I wholeheartedly
support them for volunteering.
To argue that more could have been done before the incident is to speak
agreeably of hindsight. Let us seek to do our utmost for those who act
in such altruistic fashion. Though be it for monetary gain, it is still
no less altruistic if you concede that it is better for some to gain for
their work and many benefit than for none to benefit at all. Medical advances
seek to provide the best treatment possible. When confronted by illness,
knowing you receive the best treatment that can be offered is a powerful
source for hope to beat the illness or reassurance to be able to live with
it. Thus it is essential that such advances continue unimpeded by suspension
or denial of trial proceedings.
A nation has an obligation to insist on the most stringent measures to
protect its population and autonomous individuals within. Not too long
ago, many of us heard of the maiden flight of the European giant Airbus.
Its dare-devil test pilots, though highly skilled, were suited up like
astronauts, kitted out with gas mask, oxygen supply and parachute and had
a fire extinguisher and a trap-door escape hatch behind the cockpit, just
in case. The contrast drawn is that the test pilots had a near perfect
fighting chance to exit at any time during the event, while the drug trial
volunteers had none — it was an all-or-nothing, absolute, near-single
point-in-time event. The important, relevant point of principle is that
near- absolute safety be paramount for those engaging in such risk.
Two obvious suggestions can be offered for consideration to reassure future
volunteers, as much as is humanly possible, of measures taken to minimise
any potential life-threatening risk:
· That administration to each individual be successive rather than
concurrent, separated by a period sufficient reasonably to discount the
worst possible acute, adverse drug reaction, notably anaphylaxis, immediate
or delayed, usually measured in a maximum time frame of days not weeks
· That trial phase I doses of biological substances be administered
to each individual volunteer by incremental bolus or gradient infusion
to titrate to the laboratory based, pre-determined, presumed safe and effective
dose
A combination of both would reduce the risk further but prolong the trial
period.
It may be necessary for pre-screening volunteers to expose their tissue
samples to the test substance before in vivo administration. This is a
similar concept to what occurs in deciding microbial sensitivity to antibiotics
before use, but opposite in intention, by seeking to establish minimal
effect on tissue samples.
If a change in how biotechnology companies ethically conduct their approach
to trials is imminent, and doubtlessly demanded by society, then an alternative
for volunteer recruitment may be suggested to reduce costs in this predominantly
venture capitalist-driven, burgeoning sector. Would we as a society consider
compulsory conscription or mandatory social duty, as in jury call-up, an
option? Such recruitment could not be imposed by a private, profit-generating
business, but it could be imposed by a national organisation with the power
to determine what medicines it would like to have to treat a growing need.
Perhaps the Medicines and Healthcare products Regulatory Agency or the
National Institute for Health and Clinical Excellence could be considered
to appeal to the aspirational ideals of youth to influence their world
while addressing a national necessity. Intellectual property, patent rights
and profit yields would be major factors for all concerned, not least the
biotechnology companies, to consider. Perhaps a compromise between the
current private sector undertaking with public sector involvement will
be required to off-set the cost implications for the safety we strive for
in trialling such drugs, particularly the selective and extremely potent,
immune-interacting, biologically derived substances of the future.
John Fallon
Kingston, Surrey |
The
Pharmaceutical Journal