Intended for healthcare professionals

Rapid response to:


Including older people in clinical research

BMJ 2005; 331 doi: (Published 03 November 2005) Cite this as: BMJ 2005;331:1036

Rapid Response:

Frailty is the new research priority

We also agree with McMurdo (bmj 2005; 331: 1036-7) that it is
important to include older people in medical research but there are many
obstacles to overcome. We are currently recruiting frail older patients
into a government funded (National Health and Medical Research Council of
Australia) randomised controlled trial (RCT) of a conjugated pneumococcal
vaccine versus the standard polysaccharide vaccine. Our experience
illustrates the need for such trials as we found that demented patients
were far less likely to have been offered previous pneumococcal
vaccination. Only 8/68 (12%) demented patients were vaccinated against
pneumococcus, compared to l63/265 (62%) of all geriatric patients (OR
0.08, 95% CI 0.04-0.19, p <0.0001). However, despite the low
vaccination rate among demented patients, these patients present to
hospital with acute illness and are just as likely to require hospital
admission if acutely unwell with pneumonia. We are aware of the
difficulties in recruiting such patients into RCTs as we needed a
Guardianship Tribunal approval (New South Wales, Australia) before we
could approach a “person responsible/friend” for consent. This substantial
additional RCT preparation is a major disincentive for including such
people. We agree that research screening, consenting and maintaining frail
older people in RCTs requires more time than for younger “fitter” people.
We believe short, simply written information is a key component in
facilitating appropriate discussion during the consent process. We are
concerned at the complexity of some trial information leaflets recommended
by ethics committees and the pharmaceutical industry.1

The other major theme of the editorial was the fear that the co-
morbidity of older people will inversely affect the balance of risks and
benefits. However, the elderly may have more to gain from treatment
(compared to younger people) as they usually have an increased absolute
risk of poor outcome from the index disease, despite potential increased
risks of treatment. The key aspect of trial design for the 21st century is
how to quantify frailty in the new generation of trials in older people?
In our pneumococcal trial we have opted to measure frailty using a
“Frailty Index”.2 The “Frailty Index” is a very simple summation of 35-40
different deficits that become more frequent in old age, and recent work
has shown that this index has important predictive properties.2 The exact
number of items in the Index isn’t as important as having a sufficient
range across a variety of deficits. As an illustration, the data from the
first 60 patients recruited in our trial is as follows: age range 62 to
100 years; Mini Mental Status Examination Score 7 to 30 (Median 26);
Barthel Index 30 (moderately disabled) to 100 (functionally independent)
with median of 85; and the Frailty Index has ranged from 2 to 24 (maximum
frailty score 40). Unlike the Barthel Index and Mini Mental Status Exam,
the Frailty Index does not appear to have a “floor” or “ceiling” effect
for our frail population, and thus appears to be a useful measure.
Overall, our experience is that it is feasible to recruit frail older
people, provided you invest in the extra time to set up the trial and have
appropriate research resources to recruit and retain participants.

Finally, could another major factor that prevents the involvement of
older people in research be the view that they are “unworthy” of
treatment? This may be a factor in our finding that demented patients are
significantly less likely to be vaccinated, and is certainly our anecdotal
experience when arguing for preventive measures such as vaccination in
this group. Whilst we would agree that older people represent core
business for health services (and increasingly so in the future) we would
suggest that “frailty” is the core research business for geriatricians and
other researchers. We need to invest in better ways to quantify frailty
and society needs more research and RCTs that will be generalisable to the
types of patient we see in our clinics and hospitals.

1 Paasche-Orlow MK, Taylor HA, Brancati FL. Readability Standards for
Informed-Consent Forms Compared with Actual Readability. N Engl J Med
2003; 348: 721-6

2 Mitnitski AB, Mogilner AJ, MacKnight C, Rockwood K. The Mortality
Rate as a Function of Accumulated Deficits in a Frailty Index. Mech Ageing
Dev 2002; 123: 1457-1460

Competing interests:
None declared

Competing interests: No competing interests

13 December 2005
Richard I Lindley
Professor of Geriatric Medicine
Raina MacIntyre and Iman Ridda
Westmead Hospital (C24), The University of Sydney, NSW 2006, Australia