prescribing accounted for 19–36% of hospital
admissions due to drug-related adverse events.
To compound this worrying situation, there is the
concomitant use of over-the-counter (OTC) nonpre-
scription drugs. Only 50% of physicians or health
workers ask about OTC drug use, yet 40% of all
drugs used by the elderly are nonprescription drugs.
In all, 69% of the elderly use OTC drugs, and 70%
take at least one prescription, as described earlier. In
addition,31% take alcohol frequently (Conn, 1992).
Thisnewpotential for adversedruginteraction is
enormous. Interaction of NSAIDs and aspirin with
anticoagulants, such as warfarin or coumadin, can
increase the bleeding tendency, and not just from
the stomach. Antacids can decrease the excretion
of antidepressant tricyclics, quinidine, pseudoe-
phidrine and indomethacin. They can also reduce
the absorption of digoxin andb-blocker hyperten-
sive medication. These are only a few of the
multitude of interactive drug effects. This is
imposed on the reduced efficacy of hepatic meta-
bolism and elimination, and renal excretion in the
elderly (on average, about 30% reduction). Thus,
drug OTC use can add to the recipe for toxic drug
accumulation and, in the latter case of antacids,
cause further damage to the kidney by loss of blood
pressure control and worsening cardiac failure.
15.4 Practical and ethical issues
of drug research in older
populationsTraditionally, elderly subjects were frequently
excluded from clinical drug development (unless
the disease being treated was more prevalent in
that age group). The reasons given were that the
elderly suffer from too many other diseases,
require concomitant medicines, are more frail
and are more vulnerable to adverse events. All
these can cause ‘static’ in the interpretation of the
data, and give undue weightage to adverse events
in the labeling and product package insert.
In addition, the elderly can exhibit differences,
both physiologically and pathologically compared
with the younger population; the contrast in speed
of disease progression of prostate cancer in the
‘younger elderly’ compared to the slow rate in
the ‘older old’, is an example. The elderly are
often confused or demented, making informed
consent and their continuation in a study question-
able. Lastly, because the elderly indication may
represent only a small use of a drug, it is
uneconomic to include the elderly in a drug’s
development program. These are often the
perceived concerns of both investigators and phar-
maceutical firms.
What is ‘geriatric’? Strictly defined, it describes
aperson aged 65years or over, butaging is neithera
homogeneous nor a linear process. There are very
fit 80-year-olds who climb mountains, and young
children dying from genetic advanced aging (pro-
geria). The elderly therefore cover a spectrum of
fitness. So many of the above concerns can be
reduced by selecting ‘uncomplicated, healthy’
older patients in phase I studies, who are increas-
ingly available due to the success of medicines and
preventative medicine.
However, there is a need to know how medicines
behave in the real world – not just their interactions
with other medicines butalso in other disease states
suffered concurrently, which is often the case in a
geriatric population and less so in younger age
groups.
For the elderly, of equal importance to life exten-
sion and cure is improvement or preservation of
their activities. Thus, the results of quality of life,
disease outcomes and pharmacoeconomic studies
are of even greater relevance to this special popula-
tion and to third-party payers.15.5 Regulatory response
By the 1980s, most of the new medicines still had
little or no information on elderly dosing or con-
tained disclaimers. As a result of this, and the fact
that 30% of prescription drugs by then were con-
sumed by just 12% of the population (those over
65 years), a new guideline was issued. Thus, the
FDA Guideline on Drug Development in the
Elderly(1990) recommended that, if a drug was
likely to have significant use in the elderly, then
studies should be done in an elderly population.
These studies should look at effectiveness and15.5 REGULATORY RESPONSE 195