Healthy Skepticism AdWatch

AdWatch illuminates the logical, psychological and pharmacological techniques used in drug advertisements.

December 2003, Australia

Feedback on Nexium (esomeprazole) from AstraZeneca

This report is based on feedback from 142 people who participated in AdWatch during 26 September to 13 December 2003.

Summary How many participants: When, Why and Who? Evaluations of AdWatch Revised recommendations for treatment of reflux esophagitis Evaluations of the Nexium advertisement Other themes in the comments Plans Opportunity to comment

Summary

Our first AdWatch focused on an advertisement for the proton pump inhibitor (PPI) esomeprazole (Nexium) for reflux esophagitis. This report is based on feedback from 142 people who participated in AdWatch during 26 September to 13 December. About half of the participants were doctors and a quarter were pharmacists. 93% of participants rated AdWatch as helpful. Most comments were positive but there was some disagreement with our recommendations for treatment of reflux esophagitis. We have revised our recommendations. 76% of participants rated the Nexium advertisement as misleading but there were no positive comments. Negative comments included coverage of the implications for AstraZeneca, and the pharmaceutical industry as a whole as well as concerns about Direct to Consumer Advertising. There were comments about gifts for doctors, personal experiences of medical care and whether or not drug advertisements are influential. Of the 37 participants who prescribed Nexium sometimes or often before reading AdWatch on Nexium, 30 planned to prescribe it less often.

How many participants - When, Why and Who?

There were 7,653 visits to the AdWatch on Nexium webpage from 26 September to 13 December. The three peaks follow publicity after the AdWatch launch on 1 October (especially an email posting to AusPharmList on 8 October) and a report in the British Medical Journal (BMJ) on 18 October (link to BMJ report) an Associated Press report in several Australian newspapers on 21 October (link to report in The Advertiser) and an endorsement from Phillip Adams in the Weekend Australian Magazine on 8 November (link to Phillip's column). We will submit this data to formal time series analysis. The BMJ report and Phillip's column were also the most effective sources of new subscribers for Healthy Skepticism during 2003. During those 79 days 214 people participated by responding to AdWatch questions. Of those participants 142 gave consent for their feedback to be included in data for research reports. This report is based on the feedback from the 142 consenting participants. AdWatch is not designed for generalisation of findings like a survey. We evaluate all feedback on its own merits like letters to the editor of a medical journal. Regardless of whether an item of feedback represents majority or minority views we are interested in what we can learn from it to help us improve our capacity to reduce harm from misleading drug promotion. Participants were:

2	1.4%	no occupation specified
74	52.1%	doctor
2	1.4%	journalist
5	3.5%	medical student
9	6.3%	member of the public
6	4.2%	other health professional
4	2.8%	pharmaceutical industry employee
33	23.2%	pharmacist
3	2.1%	pharmacy student
4	2.8%	other

Evaluations of AdWatch

Participants’ evaluations of AdWatch on Nexium were:

3	2.1%	No answer
0	0.0%	No opinion
132	93.0%	More helpful than misleading
5	3.5%	Neutral
2	1.4%	More misleading than helpful

Having 93% of participants rate AdWatch on Nexium as more helpful than misleading is encouraging. Positive comments included:

"Thank you for demonstrating the conflicting details which few of us professionals take the time to evaluate ourselves." "Valuable information, especially regarding the subtle changing of spelling to suggest that a different drug is being prescribed." "Good summary of available literature and evidence-based management guidelines." "I hope this site continues. It has been very useful for me and I hope that my critical analysis skills will be improved." "I appreciate the careful point by point way you moved through the ad. Much better than a blanket, "Gosh, isn't this awful!"" "Your criticisms seem suitably restrained and careful, therefore valuable" "Comprehensive explanation given. Gives a practical solution to prescribing and does not just highlight the problem." "It should be compulsory for all GPs to read this!"

A staff member of a drug company (not AstraZeneca) commented:

"This is a great concept – and will support the industry in self-regulation"

Some participants planed to tell others about AdWatch:

"This is a great service! I'm going to pass it around to my medical school classmates." "Takes the work of MaLAM [the predecessor of Healthy Skepticism] more to the coal face. I will be spreading this around widely to my colleagues."

Personal endorsement promotion by word of mouth and "word of mouse" (internet) can be very effective so we are particularly grateful for these comments. One participant who rated AdWatch on Nexium as helpful nevertheless had several suggestions for improving future issues. We will respond to each point:

"Should have a brief summary of the points made."

Will do from now on.

"Not clear whether or not the histogram comes from a Nexium ad or elsewhere."

The histogram was produced by the AdWatch team from the data provided by the study cited by the advertisement. (link to histogram) Since then we have seen similar histograms in Nexium advertisements but they are misleading because they lack error bars.

"Should say why this ad was selected. Did someone complain about it? Do producers of AdWatch think it is particularly deceptive? Does it represent a major misuse of money available for drug therapy?"

This advertisement was selected by a clinical pharmacologist who wrote: "I was aware that the issue of specific isomers was being used as a "patent extender" by some companies, and that the advertising for Nexium was proving very successful (based on my observations of the PPIs being used at [one] hospital, anyway) with very little scientific basis. So it seemed to me to be a good illustration of a couple of important principles." We plan to select most advertisements at random and allow visitors and participants to judge the advertisement and our analysis for themselves. Some participants requested that AdWatch be less complex. Unfortunately the issues involved are complex but we will do the best that we can. We also received constructive criticism from two medical journalists. One pointed out that the Therapeutics Initiative (link) recommends reducing the costs of PPIs by using half tablets of the larger doses.[1] The other medical journalist pointed out that whilst it was reasonable for us to describe the disclosure of the low comparison doses as being "in the fine print" for the particular advertisement we randomly selected this is not so clear for other versions of the same advertisement. Other versions still have the disclosure statement at the top of the fine print section of the advertisement but in a relatively larger font. Five participants rated AdWatch on Nexium as neutral. We will focus on what we can learn from the most critical comment:

"It is not a good idea to respond to "half truths" with other half truths. Elevation of the head end of the bed surely went out 30 years ago (if it were ever adopted seriously) and H2 receptor antagonists have only a fleeting and diminishing effect with time. As for other lifestyle changes just what does your author have in mind that will compare in any way to the use of a proton pump inhibitor for the control of oesophagitis? It would be best to refer to original articles rather than reviews where the same old myths and misconceptions can be wheeled out with little or no justification. The overall idea is fine, but if you are going to criticize, please be sure that the criticisms are valid."

We should have cited an original study of elevation of the head of the bed for reflux esophagitis. For example one trial comparing placebo with ranitidine or elevation of the head of the bed or both for severe (grade III) reflux esophagitis found that both treatments were effective but the combination was significantly more effective than either alone.[2] The combination is adequate for many people with less severe esophagitis and much cheaper (AUD $ 22.85 for 60 ranitidine 150mg vs AUD $ 150.52 for 60 esomeprazole 40mg). Most people with reflux esophagitis seen in general practice have mild disease whereas gastroenterologists tend to see people with more severe disease. For more severe disease we recommend starting with a PPI and only going without PPIs if they are not needed. Two participants rated AdWatch on Nexium as more misleading than helpful. One was a pharmacist who also rated the Nexium advertisement as misleading and provided no other information. The other was a doctor who previously prescribed Nexium often and planed to continue prescribing it often. He or she commented that: "Your 'dose' argument is blatantly flawed. All of those PPIs listed are different compounds, chemical entities with different biochemical profiles. How can you assume 40mg A = 40mg B ?" What we wrote was "esomeprazole 40mg is unlikely to have any clinically significant advantages over pantoprazole 40mg." That was mostly based on the only trial we were aware of that made that compared those drugs in those doses. In that trial people with oesophageal reflux class B or C (A is less severe, D is more severe) had "first adequate relief" from daytime symptoms on average at 3.7 days in the pantoprazole 40mg group (n=112) and on average at 5.9 days in the esomeprazole group (n=105) (p= 0.034).[3] The initial response from AstraZeneca was that they had "no objection to any part of Adwatch on Nexium". However we are having ongoing dialogue with AstraZeneca. That company has recently sent us a poster report of a second study comparing the same drugs at the same doses. The poster reports that people with oesophageal reflux of all classes had "sustained resolution of heartburn" on average at about 8 days in the pantoprazole 40mg group (n=1594) and on average at about 6 days in the esomeprazole group (n=1567) (p<0.001).[4] A subgroup analysis of crude healing rates at 4 weeks suggests that esomeprazole was not more effective than pantoprazole for people with grade A (mild) reflux esophagitis but was more effective for people with grade D (severe) reflux esophagitis. Possible explanations for why these two trials found opposite results include random variation and bias in one or both trials. We can only conclude that we do not know which drug is more effective but a major difference is unlikely. Even if esomeprazole relieves symptoms about 2 days faster that would not justify paying AUD $ 903.12 per year for Nexium 40mg (esomeprazole) ,perhaps for many years, rather than AUD $ 582 per year for Somac (pantoprazole) 40mg. However for the rare patients with persisting symptoms despite pantoprazole 40mg it would be appropriate to try esomeprazole 40mg to see if it did any better for those individual patients. One participant asked: "Why did you choose esomeprazole for your "best value approach" rather than a cheaper drug?" In Australia whole tablets of esomeprazole (Nexium) 20mg tablets have been priced cheaper than the whole tablets of other PPIs of similar effectiveness. Rabeprazole (Pariet) 10 mg, omeprazole (Losec) 10 mg and lansoprazole Zoton 15 mg are cheaper but may be less effective. However half tablets of pantoprazole (Somac) 40mg are much cheaper than whole tablets of esomeprazole (Nexium) 20mg (AUD $ 24.25 for 30 of ½ Somac 40mg vs $ 46.19 for 30 of whole Nexium 20mg). We do not know of any comparisons of those drugs at 20mg doses but the evidence discussed above suggests that it is unlikely that esomeprazole has a large enough advantage over pantoprazole to justify the price difference.

Revised recommendations for treatment of reflux esophagitis

In response to all the feedback received we have improved our current recommendations for Australia to the following: Please note that these recommendations may not be appropriate in other countries if the relative prices are different and will no longer be appropriate for Australia if the prices change or if new drugs or new evidence justifies changes. For severe reflux esophagitis (grades B, C and D):

Recommend lifestyle changes for all patients including elevation of head of bed, no smoking, no heavy alcohol intake.
Commence therapy with pantoprazole 40mg (Somac).
If symptoms are not controlled try esomeprazole 40mg (Nexium).
If symptoms are controlled then try half tablets of pantoprazole 40mg (Somac). If that is effective then try a H2 antagonist such as ranitidine (Multiple brands).

For less severe reflux esophagitis (grade A):

Recommend lifestyle changes for all patients including elevation of head of bed, no smoking, no heavy alcohol intake.
Commence therapy with half pantoprazole 40mg (Somac).
If symptoms are not controlled try pantoprazole 40mg and if that is not effective then try esomeprazole 40mg (Nexium).
If symptoms are controlled then try half tablets of pantoprazole 40mg (Somac). If that is effective then try then try a H2 antagonist such as ranitidine (Multiple brands) and if that is effective then try lifestyle measures alone.

Evaluations of the Nexium advertisement

Participants’ evaluations of the Nexium advertisement were:

6	4.2%	No answer
6	4.2%	No opinion
9	6.3%	More helpful than misleading
13	9.2%	Neutral
108	76.1%	More misleading than helpful

There were no positive comments about the advertisement and 6 of the 9 participants who rated the advertisement as helpful nonetheless planed to prescribe or recommend Nexium less often after reading AdWatch. One participant's comment on this question was:

"Not very clear what you mean in the above statement - are you asking directly about the ad or the opinion of Adwatch on the ad?"

We were asking for a rating of the advertisement but our question was not clear for some participants so we will try to improve the wording for the next issue. Negative comments included:

"Slimy! Dishonest!" "Designed to encourage consumption rather than educated and responsible prescriptions" "Meant to deceive unsuspecting people" "not a bit useful in helping with patient care decisions." "In general I find these sort of glossy ads with big pictures unrelated to the drug and very short on factual information insulting. Do the companies really think Doctors are going to prefer glossy channel 10 [Australian popular down market commercial television] style ads to peer reviewed evidence? Or maybe they do, and I am missing something?"

Advertisers do not aim to satisfy our style preferences. They use the techniques that they have found to be the most effective for influencing us. (For an advertising executive’s perspective link to Garai's challenge: The 40th anniversary of the inspiration for Healthy Skepticism)

Comments from participants on implications

First, for AstraZeneca:

"I had always thought Astra were one of the more ethical companies. Disappointing that they have to resort to misleading advertising too." "A complete con. While I have seen reps re Nexium they have never mentioned the finer details; funny that." "After reading information from this site and from AstraZeneca's website I am left wondering several things. 1. Is the content of the Nexium advertisement and therefore the seemingly inappropriate comparisons the responsibility of the advertising agency or AstraZeneca? [AstraZeneca is responsible.] 2. If the responsibility for the misleading information lies with AstraZeneca can we assume that information regarding their other products is also questionable?"

Second, for the pharmaceutical industry as a whole:

"Because of this kind of misleading information, pharmaceutical advertising should be closely regulated.." "What do you expect? It's an ad! It would be extremely naive to expect objective information."

Third, for Direct to Consumer Advertising:

"Well done!! Keep up the good work! The amoral and immoral actions of drug company management, needs to be reined in. Hopefully, direct-to-consumer-advertising can be halted in Australia, before any harm can be done." "Again, semantic above substance - woe to the day we move to direct to consumer advertising."

Other themes in the comments

There were several other themes in the comments including: Are drug advertisements influential?

"Completely misleading! No wonder I ignore these ads." "I was already aware of the issues so knew not to pay the advert too much attention." "I feel I would not be swayed by the advert." "I would like to think that unless there are NNT or absolute risk percentages then I tend to ignore the "information" in drug ads and go to sources such as the therapeutic guidelines, AMH [Australian Medicines Handbook] and Datis [Drug and Therapeutics Information Service]." "Don't read the ads, but as you say, they sneak in!" "As a hospital pharmacist I see a great many patients on Nexium who think it is "much stronger and better " than Losec. Clearly this misleading advertising is working!!!" "Typical half truths and unsupported assumptions. Unfortunately had me sucked in for a period but no longer."

Using information from independent sources and not using information from drug companies is associated with better prescribing but unfortunately giving advertisements little attention can enable them to mislead by allowing the messages in under the critical appraisal radar. Realising that one has been mislead has been shown to be a key step towards improving one's ability to avoid being mislead in the future. (link to Med J Aust December 2003 article explaining the ideas behind AdWatch) Gifts for doctors

"Incidentally, I have tried to get our GP Division (I am CME chair) to ban reps, displays, show bags, trained monkey "talks" on a new drug, T-shirt hunts, big blue Viagra paper weights, funding etc from our CME meetings. But guess what? The other docs don't care and don't want to cause offence. Ah well, I just need to keep walking out when they get up and offend us and go out and buy my own lunch!"

Personal experiences of medical care

"Losec was prescribed for me some (8) years ago with comment "You'll be using this for life". That got my hackles up. I followed the prescribed dose (for 5 months!) and then changed my habits. More salads, less meat, sleep on left side. Severe hiccoughs did occur (an apple was worst offender) but now reflux is a thing of the past unless I get careless when faced with some enticing cuisine."

Plans

Before reading AdWatch on Nexium participants:

44	31.0%	no answer
54	38.0%	prescribed
33	23.2%	recommended
11	7.7%	took

Nexium:

41	28.9%	no answer
16	11.3%	often
42	29.6%	sometimes
43	30.3%	never

for gastro-oesophageal reflux disease. Having read Adwatch on Nexium, participants planned to prescribe, take or recommend Nexium:

49	34.5%	no answer
64	45.1%	less often
27	19.0%	as often
2	1.4%	more often

Of the 13 participants who prescribed Nexium often before reading AdWatch on Nexium, 12 planed to prescribe it less often. Of the 24 participants who prescribed Nexium sometimes before reading AdWatch on Nexium, 18 planed to prescribe it less often. It is possible that participants may have planed to make changes but not implemented those plans (and vice versa). It is also possible that visitors to the AdWatch webpage who did not participate may have implemented changes. In the future we will be asking visitors if they have a system for tracking if they make changes or not. 42 participants wanted their name to be sent with their feedback to pharmaceutical companies and regulatory agencies. We appreciate this very much because we believe it will give the feedback more credibility. We also understand that many people have compelling reasons for keeping their participation in AdWatch confidential. All participants’ feedback will be kept confidential unless permission is given for disclosure.

Opportunity to comment (Closed 22 February 2004)

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