Principles and Practice of Pharmaceutical Medicine

(Elle) #1

thrombolytics in case of cerebral thrombosis. As of
1999, more than 20new drugs were in development
to treat this condition.
Arthritiscausinginflammatory and degenerative
changes around joints affects 43 million in the
United States, and CDC projects that this will
rise to 60 million by 2020. It can be caused by
more than 100 different diseases, but the common-
est are osteoarthritis and rheumatoid arthritis. New
medications, such as the anti-tumor necrotic factor
a-blockers, raise fresh challenges to clinical study
methodology because of limitations on nonclinical
toxicity predictors and the application of biologic
measurements on a traditional drug appraisal
system.
The new nonsteroidal anti-inflammatory drugs,
including the Cox II inhibitors, because of the vast
range of arthritic diseases, require that careful
selection of indications for initial product approval
must be undertaken. Rarely do companies have the
time or money to develop all the pain indications
(acute, chronic use) or to study arthritic diseases
prior to product launch. As with hypertension, the
numbers of patients required in the databasewill be
large for product approval, especially for safety.
Depressionis a frequently missed diagnosis in
the elderly. The Alliance for Aging Research says
that 15% of Americans aged 65 years and older
experience clinically relevant depression. It can
amplify the underlying disabilities in stroke, arthri-
tis, Parkinson’s disease, slow or prevent recovery
from hip fracture and surgery, and be mimicked or
masked by an underactive thyroid. The latest
receptor-specific medicines have a very much
reduced potential for adverse events and drug inter-
actions. Difficulties can arise from confusion,
memory impairment and disorientation, which
are common in the depressed elderly. This brings
challenges of ensuring both drug compliance and
follow-upattendancein clinical studies.It also may
require guardian co-signature for informed wit-
nessed consent.
Parkinson’s diseaseaffects more than 1 million
Americans and about 4 in every 100 by 75 years of
age. Ten new drugs are under development. The
patients may become very physically disabled but
still retain a clear sensorium until the very end
stages of the disease. Thus, drug compliance and


follow-up visits are easier to achieve than with
Alzheimer or depressed patients.
Alzheimer’s diseaseis the eighth leading cause
of death in the elderly and already affects some 4
million Americans. The incidence rises from 2% at
65 years to 32% at age 85. The National Institute of
Health (NIH) estimates that at least half of the
people in nursing homes have this disease. A
small study of donezil showed that this treatment
avoided the need for home nursing care by half
compared to those who did not receive the medi-
cine (Small, 1998).
Clinical studies in this disease are very expen-
sive, often requiring several collaborating disci-
plines at each investigative site. A gerontologist,
aneurologist,a psychologistandapsychiatrist may
be required, in addition to the usual support staff.
Multiple cognitive tests and behavioral ratings of
the patient often involving primary caregiver rat-
ings will be required – all this in addition to the
basic Alzheimer’s Disease Assessment Scale
(ADAS–COG). These studies, at present, require
large numbers of patients to show the often small
improvement, as well as months of observation to
detect a slowing of progression. These studies
require large numbers of patients, and many are
conducted at multinational sites. It must be asked if
cognitive scales are validated in different cultural
backgrounds.

15.9 Issues in the conduct
of clinical studies
in the elderly

Informed consent


In general, the principles are no different with the
elderly than with other adult persons; the elderly are
just as subject to the relationship to the researcher if
the clinician and researcher are one and the same.
Not wishing to offend (by refusal) is very strong in
the elderly, and also they are also subject to ‘ther-
apeutic fallacy’, that is they find it hard to accept
that, despite repeated descriptions of risks and pos-
sible benefits, the treating physician could be really
offering them treatment of uncertain benefit or risk.

198 CH15 DRUG RESEARCH IN OLDER PATIENTS

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