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I am writing about a recent advertisement for desmopressin (DDAVP spray) as a treatment for night-time enuresis. Your readers may wish to refer to the advertisement. It features a young boy in red superhero pyjamas with a bed in the background. The young boy is smiling and displaying a very confident demeanor. Overall, it is an attractive and eye-catching advertisement that effectively captures the joy and confidence that children display when they overcome bedwetting.
The advertisement is deceptive and misleading. It claims that DDAVP spray causes children to be dry after treatment. In other words, it claims to cure enuresis. The headline proclaims “In just 3 months with DDAVP, the real superhero could be the one wearing the pyjamas”. The second sentence states “Recent studies show that 3 months of daily therapy with DDAVP Spray can end bedwetting”.
A reasonable professional reading this advertisement would interpret that ‘ending bedwetting’ means that even when discontinued, DDAVP spray ends bedwetting. There is nothing in the advertisement that would suggest otherwise. Indeed, this is the interpretation that Ferring Pharmaceuticals (North York, Ontario), the manufacturer of the drug, has made (Dr Anne Brusby, personal communication, 1999).
The data cited in support of the claim to end bedwetting are from the SWEET study. The study was originally published in 1995 by Hjalmas (1) in a company-sponsored supplement in the Scandinavian Journal of Urology. Subsequently, virtually the same study with the addition of eight subjects was published in the British Journal of Urology in 1998 by Hjalmas et al (2).
The SWEET study (1,2) was an open, multicentre trial in which children aged six to 12 years were recruited. Following an observation period of four weeks, 399 children entered a dose-titration period on nasal desmopressin. If the number of wet nights decreased by more than half, they began a long term treatment study of desmopressin. There was no control group. The medication was interrupted for one week every third month for a year. During these off-medication weeks, 77 children (19% of the inception cohort) were dry for a week.
Because of two significant methodological problems, these data in no way support the claim that desmopressin ends bedwetting. The first problem is that a placebo or no-treatment group was not used. Consequently, one cannot determine if the one-week remission rate after periods of treatment is greater or less than the placebo response or the natural history of the disorder. Hjalmas et al (2) note that the 19% response rate in their study might be an underestimate because data from the last period following a period of treatment were not included in their study. In any case, historical controls are inadequate to make claims such as those made by the company.
The second problem is that the typical definition of the cure or successful treatment of bedwetting is several-fold longer than the one week of being dry used in the SWEET study. Ferring has said that six months of dryness is the standard definition (Dr Brusby, personal communication, 1999). I concur with this. Consequently, using standard outcome criteria, the SWEET study provides no data at all on the ending of bedwetting.
It is clear that the evidence cited does not demonstrate that desmopressin ends bedwetting once the drug is discontinued. I know of no other data that would support this claim. However, when I contacted Ferring explaining the reasons why their claims were not supported and requesting a correction of their advertisement, the company claimed that the SWEET study did show long term effectiveness, and that the advertisement was approved by the Pharmaceutical Advertising Advisory Board (PAAB) (Dr Brusby, personal communication, 1999).
I do not dispute the effectiveness of desmopressin while the drug is being taken, nor do I challenge the safety of the medication.
I would appreciate it if Paediatrics & Child Health would publish this letter so that readers of the journal can make their own judgment.
REFERENCES
1.Hjalmas K. SWEET, the Swedish Enuresis Trial. Scand J Urol Nephrol Suppl. 1995;173:89–92. [PubMed] [Google Scholar]
2.Hjalmas K, Hanson E, Hellstrom AL, Kruse S, Sillen U. Long-term treatment with desmopressin in children with primary monosymptomatic nocturnal enuresis: an open multicentre study. Swedish Enuresis Trial (SWEET) Group. Br J Urol. 1998;82:704–9. doi: 10.1046/j.1464-410x.1998.00826.x. [DOI] [PubMed] [Google Scholar]
The letter written by Dr McGrath highlights the importance of having vigilant critical readers who draw concerns to the attention of the appropriate governing bodies.
The Pharmaceutical Advertising Advisory Board (PAAB) is a self-regulatory mechanism adopted by the Canadian pharmaceutical industry and Health Canada for approving pharmaceutical advertisements. All pharmaceutical advertisements running in Paediatrics & Child Health must be PAAB approved. The PAAB approval for this particular advertisement, however, expired in January 1998.
At Dr McGrath’s request, PAAB reviewed the advertisement and his specific concerns. The PAAB complaint ruling was based on the fact that there is a perception that the efficacy of DDAVP has been overstated because of inappropriate wording and a lack of supporting information for that wording. Therefore, the advertisement was deemed “not accurate, complete and clear”. Ferring was instructed to cease distribution of this advertisement, and submit the advertisement within five working days for current PAAB review and acceptance in accordance with the ruling on this complaint.
We applaud Dr McGrath’s vigilance and tenacity in this matter.
I would like to clarify some of the issues that have been raised with respect to our advertisement for desmopressin (DDAVP Spray).
Ferring has always been committed to providing effective treatment options for nocturnal enuresis, and has used the advertisement in question for the past three years to enhance awareness of DDAVP.
Recently, Patrick McGrath PhD claimed that our advertisement was misleading. We disagree with Dr McGrath’s opinions on this matter and with Dr MacDonald’s remarks on the subject.
Several studies are available that support our view that desmopressin can cure nocturnal enuresis. Observations were made in early desmopressin studies that a higher number of patients remained dry after a course of treatment compared with the spontaneous annual cure rate of 10% to 15%.
Dr Kenneth Miller et al (1) found that 35% of desmopressin responders remained dry when desmopressin was stopped. The SWEET study (2) was designed to evaluate the long term benefits of continuous desmopressin. Through the one-year, long term trial, 75 of the 242 study patients (31%) achieved one dry week off desmopressin during one of the four treatment-free windows.
This outcome demonstrates that relatively short term, continuous nightly desmopressin can result in lasting dryness. The Word Health Organization’s recent publication Incontinence (3) makes a similar observation: “The message of the SWEET study is that if the child has an initial response with more than 50% reduction of wet nights, the lasting cure rate can be as high as 31%.”
In a review article, Dr Kelm Hjalmas (4) states a cure rate of 22% based on prospective trials with four times 12-week treatment periods with follow-up of at least six months after treatment cessation. This rate is greater than the spontaneous cure rate of 15%.
Other studies have recently been completed that further support the curative benefit that can be achieved with DDAVP responders beyond the natural resolution. Other studies are currently underway to evaluate further treatment durations, withdrawal strategies and their influence on pathogenic factors.
The DDAVP advertisement has never been called into question by the medical community or PAAB in the three years that it has run. In fact, the advertisement received PAAB clearance when it was first created. Due to administrative changes at Ferring and its advertising agency, the annual resubmission for PAAB approval was not submitted on time. Ferring assumes full responsibility for this and will ensure that the necessary PAAB approval process is followed for any future advertising.
Ferring remains committed to being a leader in the treatment of noctural enuresis and will continue to share study results with the medical community in an accurate and responsible manner.
REFERENCES
1.Miller K, Goldberg S, Atkin B. Nocturnal enuresis: experience with long term use of intransally administered desmopressin. J Pediatr. 1989:723–6. doi: 10.1016/s0022-3476(89)80888-1. [DOI] [PubMed] [Google Scholar]
2.Hjalmas K. SWEET, the Swedish Enuresis Trial. Scand J Urol Nephrol Suppl. 1995;173:89–92. [PubMed] [Google Scholar]
3.Abrams P, Khoury S, Wein Alan, editors. Incontinence. St Helier: Health Publications Ltd; 1999. [Google Scholar]
4.Hjalmas K. Desmopressin Treatment: Current status. Scand J Urol Nephrol. 1999;(Suppl 202):70–2. doi: 10.1080/00365599950510274. [DOI] [PubMed] [Google Scholar]
