Electronic letters to:

Review:
Nathan Herrmann, MD and Serge Gauthier, MD
Diagnosis and treatment of dementia: 6. Management of severe Alzheimer disease
CMAJ 2008; 179: 1279-1287 [Abstract] [Full text] [PDF]
*eLetters: Submit a response to this article

Electronic letters published:

[Read eLetter] Response to Dr. Schneiderman
Nathan Herrmann   (29 January 2009)
[Read eLetter] A profoundly flawed recommendation
Henry Schneiderman   (16 January 2009)

Response to Dr. Schneiderman 29 January 2009
Previous eLetter Top
Nathan Herrmann
Sunnybrook Health Sciences Centre

Send letter to journal:
Re: Response to Dr. Schneiderman

nathan.herrmann{at}sunnybrook.ca Nathan Herrmann

We appreciate the careful reading and thoughtful comments of Dr Schneiderman. His opinion that the recommendation of the Third Canadian Consensus Conference on the Diagnosis and Treatment of Dementia (CCCCDTD3) to use cholinesterase inhibitors and/or memantine in severe Alzheimer disease(1) is “profoundly flawed”, appears to based on his concerns that the recommendation was derived from “tainted” drug company studies. Interestingly, he confirms the existence of four studies, indicating there was RCT data on which to base the recommendation, and admits the studies were published in reputable journals after peer-review. Unfortunately, while Dr Schnieiderman seems preoccupied with the sponsorship of the studies, he makes no comments about the inclusion/exclusion criteria, the randomization, blinding, outcome measures and statistical analyses, all things that were painstakingly examined by members of the CCCDTD3. For Dr Schneiderman then, any study produced with sponsorship by the pharmaceutical industry, regardless of their scientific rigor, should be ignored, and expert consensus conference recommendations should only adopt guidelines that derive from studies from a “believable scientific source”. We fundamentally disagree with this opinion, and caution Dr Schneiderman that should his stance be accepted there would be little in the way of evidence-based guidelines for pharmacotherapeutics. For example, a similarly careful review of the pivotal studies and meta-analyses on the use of cholinesterase inhibitors for mild-moderate Alzheimer disease(2) (which Dr Schniederman does not appear to regard as “profoundly flawed”) would also note the vast majority were sponsored by the pharmaceutical industry. And clearly, many (most?) other therapeutic areas are similarly reliant on industry-funded studies. Rather than disregarding this important body of knowledge, we believe the role of the expert consensus conference is to carefully review these studies to determine the quality of the design, accuracy of data analysis and their applicability to everyday use. As part of this process, determining whether there is inherent bias in the study design and interpretation is inherent. Readers will also appreciate that the language used by the CCCDTD3 for this recommendation was carefully chosen, and the need for more studies was emphasized in the Knowledge Gaps section. Rather than focus on the funding source for these studies, clinicians really need to consider what are clinically meaningful changes at this stage of the illness, the cost- benefits of these drugs, and how long they should be utilized. Until such studies are available, physicians can be reassured that the option to use these drugs in severe Alzheimer disease has merit, and is supported by both RCT data as well as Canadian expert consensus.

N Herrmann MD S Gauthier MD

References: 1) Herrmann N, Gauthier S: Diagnosis and treatment of dementia: 6. Management of severe Alzheimer disease. CMAJ 179:1279-1287, 2008 2) Hogan DB, Bailey P, Black S et al: Diagnosis and treatment of dementia: 5. Nonpharmacologic and pharmacologic therapy for mild to moderate dementia. CMAJ 179:1019-1026, 2008

Conflict of Interest:

None declared
A profoundly flawed recommendation 16 January 2009
Next eLetter Top
Henry Schneiderman
Hebrew Health Care, West Hartford, and UConn Health Center, Farmington, and Yale School of Nursing

Send letter to journal:
Re: A profoundly flawed recommendation

henrymd{at}mac.com Henry Schneiderman

The Review by Herrmann and Gauthier is chock-full of helpful information for both generalists and geriatricians.

However, the authors recommend continuing cholinesterase inhibitors or memantine even in advanced dementia. I have tracked down four of the five articles that constitute this Review's references 49-53. Two were published in Neurology, one in Lancet, one in the Journal of the American Geriatric Society--all highly respected journals. They are cited near the bottom of column 1, page 1284, as a principal basis for the Third Canadian Consensus Conference's, and the authors', recommending the use of cholinesterase inhibitors and memantine in patients with severe Alzheimer disease or other dementias.

It is bitterly disappointing to read that Pfizer or Eisai (the drug companies that manufacture the drugs in question) sponsored ALL FOUR of these studies, in whole or in part. In each case the article in question so acknowledged on the first or last page or both. There is even one embarrassed addendum to the effect that further payments were not fully described initially.

The conclusions drawn in each of these four papers are thus tainted and suspect because of the funding source. Hence, so is the Conference's recommendation, and that of the otherwise superb Review. Skepticism about these drugs in advanced dementia remains warranted. This is all the more pity in that every practicing geriatrician shares the misery and desperation of families who want us to use something to help mitigate the devastation of advanced dementia.

I find it unfortunate that the Consensus Conference and Herrmann and Gauthier accepted these studies as scientifically compelling. Would it not show better scientific and ethical integrity to admit that we lack unbiassed data? A drug that can't be stopped lest the patient suffer irreversible harm (page 1285, column 1, near the top) is a manufacturer's dream. When we assent that it remains useful until FAST/Global Deterioration Scale stage 7B or beyond, we become complicit, however unwillingly, in non-rational therapy with the specter of giving families false hope. We also injure the reputation of our profession for we seem, however noble our motives, to function as a salesperson for the pharmaceutical industry.

The authors so admirably and deftly cut through the tangle about neuroleptics; I beg that they employ the same rigor in considering whether donepezil and related drugs really do anything for patients with late- stage dementia. A study untouched by the drug companies would go a very long way. All physicians would like nothing better than to learn, from a believable scientific source, that these drugs do indeed help patients with advanced Alzheimer or other dementias.

Conflict of Interest:

None declared