James Malone-Lee responds to the media flurry over safety of anticholinergic drugs in elderly peopleBMJ 2011; 343 doi: https://doi.org/10.1136/bmj.d4740 (Published 25 July 2011) Cite this as: BMJ 2011;343:d4740
- James Malone-Lee, professor of medicine1
- 1Research Department of Clinical Physiology, Division of Medicine, University College London Medical School, London N19 5LW, UK
The intemperate hubbub over anticholinergic safety in elderly people, championed by the BBC on the morning of 24 June 2011, merits sober reflection.1 The focus was a paper by Fox and colleagues that was unavailable until 4 pm,2 when placed on the website of the Journal of the American Geriatrics Society. By then the media squall had dissipated. Recent UK history should deter such ill advised announcement of data through television, before it is published for peer scrutiny.
The article in question was a post hoc analysis of epidemiological data collected from older adults enrolled in the Medical Research Council Cognitive Function and Ageing Study. Participants were assessed using the mini-mental state examination (MMSE) in 1991 and 1993. The paper was published as an early online brief report, short on detail.
Anticholinergic exposure was measured crudely using a ranked ordinal scale that reflected the authors’ beliefs about drug potencies. Although the paper omitted the scale, the BBC website provided a copy. Disease burden was assessed by counting predefined self reported health conditions, to a maximum of three.
Under the banner “Deadly consequences,” the BBC reported an association between increased mortality and the use of anticholinergic drugs. Although it cautioned against confusing correlation with causation, it claimed that “other factors, such as increased mortality from underlying diseases, were removed from the analysis.” Causation was incited in press briefings throughout the day.
Those with overactive bladder were particularly concerned. This cause of urge incontinence is associated with older age, falls, fractures, urinary tract and skin infections, sleep disturbances, depression, and comorbidity. Options for treatment are few, and anticholinergic drugs are a mainstay.
Given our knowledge of this condition, it is not surprising that anticholinergic exposure correlated with older age, lower social class, former smoking, and more health conditions. Fox and colleagues claimed that they adjusted for age, sex, education, social class, number of self reported health conditions, and non-anticholinergic drugs. That is preposterous for two reasons: the between groups variances were not homogeneous, and, as the authors stated, the covariates correlated with the outcome measures. This naive inferential howler has been well characterised and lucidly explained.3 4
Fox and colleagues lavishly deployed ordinal scales. Nature is inimical to categories—biological variation is continuously dispersed. We clinicians, however, manufacture error by our wishful compulsive classifying.
Heeding the BBC, several relevant organisations welcomed the research in press statements. How could they? The data were not in the public domain? The desperate patients were directed to their GP. What were our overburdened GPs supposed to make of this cacophony? The cliché, “more research is needed,” proved dispiritingly ubiquitous but I disagree with that opinion.
When anticholinergic drugs were introduced for overactive bladder, we worried greatly about cognitive effects, constipation, and torsade de pointes, a sometimes lethal cardiac arrhythmia. Thus, safety in elderly people was carefully scrutinised using intervention studies of good clinical practice standard. The hypothesis that catalysed the scare, nurtured on BBC News, has been tested and rejected by many trials over the past two decades.5
Correlations should be quarantined from causation until the mandatory randomised studies are completed. Covariance analysis requires a health warning. Scientific data should be presented in journals, not through our overwrought press.
Cite this as: BMJ 2011;343:d4740
Competing interests: JM-L has specialised in treating urinary incontinence for 30 years and overactive bladder features in 70% of the 3500 consultations I do annually. I worked on the clinical trial programmes for terodiline, oxybutynin, tolterodine, and solifenacin—all key anticholinergics in Fox and colleagues’ study. My particular involvement concerned studies in elderly people. I have had no contacts with the manufacturers in recent days. Before 2005 Pfizer contributed to some conference expenses for my academic department. Since 2005, neither I nor my centre has accepted sponsorship from industry, in line with a general policy adopted by us that year. I have spoken and shall speak in 2011 at postgraduate study events sponsored by Pfizer and Astellas. I was and shall be paid a reasonable fee for such contributions. With other academics, I have a basic science collaboration that includes scientists working for Pfizer. We all contribute to this research enterprise equally. I see private patients and the income earned is paid into academic funds held by UCL.