Rapid Responses to:
|
|
Rapid Responses: Rapid Responses published:
-
![[Read Rapid Response]](/icons/misc/sectionDOWN.gif)
Helicobacter Pylori eradication
- DAVID D HOLLAND (25 January 2006)
-
Population screening and treatment for Helicobacter pylori
- Alexander C. Ford, David Forman, Alastair G. Bailey, Anthony T.R. Axon, Paul Moayyedi (3 February 2006)
-
A marketing ploy in the guise of clinical research?
- James Penston (4 February 2006)
-
Squeezing the balloon
- Guduru Gopal Rao, John O'Donohue, Giles Walker (5 February 2006)
-
Screening vs. testing symptomatic patients
- Brian S. Alper (5 February 2006)
-
The impact of H pylori eradication on dyspepsia, health resource use and quality of life in the Bristol Helicobacter project: authors reply
- J Athene Lane, Liam J Murray, Sian Noble, Matthias Egger, Ian M Harvey, Jenny L Donovan, Prakash Nair, Richard F Harvey (24 February 2006)
-
subgroup analysis of asymptomatic patients
- Brian S. Alper (1 March 2006)
-
A marketing ploy in the guise of clinical research? –further comments
- James Penston (3 March 2006)
|
|
|||
|
DAVID D HOLLAND, GP Blackwell Medical Centre, Blackwell England
Send response to journal:
|
Interesting paper - A few years ago my Health Authority Prescribing adviser came for his annual chat; as an exercise for that years Prescribing Incentive Scheme we agreed that I would look at my patients on repeat prescriptions for PPIs and see if we could safely transfer them from high dose omeprazole to low dose lansoprazole, specifically to reduce costs. It struck me that seeing patients for their 6 monthly medication reviews would give me the opportunity of undertaking this change, but then the practice was offered a supply of testing kits for near patient testing for H Pylori antibody testing; within a year we had done an "on the spot" test for all of our long term PPI patients and offered them Triple Eradication Therapy. One of our locally based gastro-enterologists suggested that this wasn't scientifically valid; however when I pointed out that this "test and treat" approach could save him from doing 19 out of 20 open access endoscopies he did agree to see any treatment failures quickly! The outcome of this exercise was a massive reduction in spending on PPI's and also H2 antagonists, which has persisted to the present day as shown on the 6 monthly prescribing analyses sent to us using PPA data from the PCT medicines management team. Competing interests: None declared |
|||
|
|
|||
|
Alexander C. Ford, Lecturer in Medicine and Honorary Specialist Registrar in Gastroenterology Centre for Digestive Diseases, Leeds General Infirmary, Leeds, LS1 3EX, David Forman, Alastair G. Bailey, Anthony T.R. Axon, Paul Moayyedi
Send response to journal:
|
Editor Population screening and treatment for Helicobacter pylori has been advocated as a means of reducing mortality from gastric cancer and morbidity from symptoms of dyspepsia in the community. There is evidence from one randomised controlled trial of screening in a population at high risk of gastric cancer in China that H. pylori eradication may prevent gastric cancer 1. We congratulate Lane et al on their elegant trial that demonstrates population H. pylori screening and treatment also reduces dyspepsia symptoms, but costs are higher, in those individuals assigned to eradication therapy at two years 2. Their symptom data are similar to our randomised placebo-controlled trial of population H. pylori screening and treatment carried out in Leeds, United Kingdom (the Leeds HELP study) 3, and we also found no significant differences in dyspepsia-related health care costs between the eradication therapy and placebo arms, excluding the cost of treatment 4. More recently we have followed up the individuals involved in the HELP study ten years post-randomisation to determine their total health service dyspepsia-related costs 5. At ten-year follow-up there was a mean cost saving of £65, in terms of dyspepsia-related resource use, in those assigned to eradication therapy (p = 0.03) compared to individuals receiving placebo. Though, as the Bristol study also demonstrated, there was a reduction in subsequent GP consultation rates with dyspepsia, the majority of the cost savings arose as a result of a reduction in subsequent dyspepsia-related prescribing amongst those allocated to eradication therapy, with a mean cost saving per individual of £45 (p = 0.01). Whilst these savings would not be sufficient to cover the cost of the eradication regimen used in Lane et al’s study there are other, cheaper, alternatives. In addition, there remained an absolute reduction in symptoms of dyspepsia among those assigned to eradication therapy at ten years, in the order of four percent, which was of a similar magnitude to that noted in the original trial, though this did not attain statistical significance. Our findings suggest that, as duration of follow-up increases, the savings made by population screening and treatment for Helicobacter pylori could be enough to cover the initial cost of screening, particularly as the costs of eradication therapy fall. Longer follow-up in the Bristol Helicobacter screening project would be useful. If this confirms that cost savings accrue with H. pylori eradication over time then population screening and treatment may still be warranted in developed countries with a high risk of gastric cancer. Alexander C Ford1 David Forman2 Alastair G Bailey1 Anthony TR Axon1 Paul Moayyedi3 1Centre for Digestive Diseases, Leeds General Infirmary, Leeds, UK. 2Centre for Epidemiology and Biostatistics, Medical School, Leeds University, Leeds, UK. 3Gastroenterology Division, McMaster University, Health Sciences Center, Hamilton, Ontario, Canada. References 1. Wong BCY, Lam SK, Wong WM, Chen JS, Zheng TT, Feng RE et al. Helicobacter pylori eradication to prevent gastric cancer in a high-risk region of China: A randomized controlled trial. JAMA 2004;291:187-94. 2. Lane, J. A., Murray, L. J., Noble, S., Egger, M., Harvey, I. M., Donovan, J. L., Nair, P., and Harvey, R. F. Impact of Helicobacter pylori eradication on dyspepsia, health resource use, and quality of life in the Bristol Helicobacter project: Randomised controlled trial. Br Med J 332, 199-202. 2006. 3. Moayyedi P, Feltbower R, Brown J, Mason S, Mason J, Nathan J et al. Effect of population screening and treatment for Helicobacter pylori on dyspepsia and quality of life in the community: A randomised controlled trial. Lancet 2000;355:1665-9. 4. Mason J, Axon ATR, Forman D, Duffett S, Drummond M, Crocombe W et al. The cost-effectiveness of population Helicobacter pylori screening and treatment: A Markov model using economic data from a randomised controlled trial. Aliment Pharmacol Ther 2002;16:559-68. 5. Ford AC, Forman D, Bailey AG, Axon ATR, Moayyedi P. A community screening program for Helicobacter pylori saves money: Ten-year follow-up of a randomised controlled trial. Gastroenterology 2005;129:1910-7. Competing interests: Alexander C Ford: none declared. David Forman has received speakers and consulting fees from AstraZeneca, Wyeth and Takeda. Alastair G Bailey: none declared. Anthony TR Axon: none declared. Paul Moayyedi has received speaker’s fees and research funds from AstraZeneca, Wyeth Laboratories, and Abbott Laboratories. |
|||
|
|
|||
|
James Penston, Consultant Physician/Gastroenterologist Scunthorpe General Hospital, Cliff Gardens, Scunthorpe, North Lincolnshire DN15 7BH
Send response to journal:
|
Sir Any benefit from eradication of H. pylori stems from its proven efficacy in preventing recurrence of peptic ulcers. [1] There is, after all, little evidence that it has a clinically important benefit in non- ulcer dyspepsia. [2,3] Given that only one-quarter of patients in the study by Lane et al. [4] had dyspeptic symptoms – and only a small proportion of these would have had peptic ulcers – it follows that only a small minority of patients were likely to benefit from eradication therapy. The results, therefore, were entirely predictable: although the authors repeatedly emphasized a 35% relative risk reduction in the primary end-point, only 3% of patients actually benefited from eradication therapy. Moreover, the absence of any difference in many secondary end- points – including the requirement for endoscopies, admissions for peptic ulcer and quality of life assessments – raises questions about the validity of even a 3% reduction in the primary outcome as well as reinforcing the view that the treatment did little to improve the lives of patients. Why was a study that subjected healthy individuals to potential adverse drug reactions with little prospect of any gain performed? Why was an eradication regimen based on ranitidine bismuth citrate used? Given the available evidence in 1996, such treatment was known to be much less effective than alternative regimens. [5,6] Why was there no mention of the unusually high clearance rate of H. pylori in the placebo group [7] and why was the reported eradication rate of 91% not based – as the rest of the results were – on an intention-to-treat analysis? It is surely no coincidence that the Bristol trial began less than a year after the launch of ranitidine bismuth citrate in the UK and was funded by GlaxoSmithKline, the manufacturers of the drug. At its inception in 1996, the study by Lane et al. [4] would have been expected to increase public awareness of H. pylori, raise the profile of ranitidine bismuth citrate and expand the market for eradication therapy. In the circumstances, would it really be too far fetched to believe that the Bristol study was not so much a clinical investigation as a thinly disguised marketing ploy? References [1] Penston JG. Review article: clinical aspects of Helicobacter pylori eradication therapy in peptic ulcer disease. Aliment Pharmacol Ther 1996;10;469-86. [2] Laine L, Schoenfeld P, Fennerty MB. Therapy for Helicobacter pylori in patients with non-ulcer dyspepsia: a meta-analysis of randomised, controlled trials. Ann Intern Med 2001;134;361-9. [3] Moayyedi P, Deeks J, Tallet N, Delaney B, Forman D. An update of the Cochrane systematic review of Helicobacter pylori eradication therapy in non –ulcer dyspepsia: resolving the discrepancy between systematic reviews. Am J Gastroenterol 2003;98;2621-6. [4] Lane JA, Noble S, Donovan JL, Murray LJ, Egger M, et al. Impact of Helicobacter pylori eradication on dyspepsia, health resource use, and quality of life in the Bristol helicobacter project: randomised controlled trial. BMJ 2006;332;199-202. [5] Pylorid, H. pylori and peptic ulcer. Drug & Therapeutics Bulletin 1996;34(No 9);69-70. [6] Penston JG, McColl KEL. Eradication of Helicobacter pylori: an objective assessment of current therapies. Br J Clin Pharmacol 1997;43;223 -243. [7] Harvey RF, Lane JA, Murray LJ, Harvey IM, Donnvan LJ, Nair P. Randomised controlled trial of effects of Helicobacter pylori infection and its eradication on heartburn and gastro-oesophageal reflux: Bristol helicobacter project. BMJ 2004;328;1417-19. Competing interests: None declared |
|||
|
|
|||
|
Guduru Gopal Rao, Consultant Microbiologist University Hospital Lewisham, London, SE13 6LH, John O'Donohue, Giles Walker
Send response to journal:
|
We would like to highlight another dimension that has to taken into account when discussing a 'test and treat' strategy for non ulcer dyspepsia associated with Helicobacter pylori. Neither this study nor the editorial have commented on the emergence of resistance in the commensal oral and bowel flora of the patient following treatment.1 If this resistance then spreads to pathogenic bacteria, these antibiotics will cease to be useful in a variety of infections.2 In the past decade, there has been a substantial increase in resistance to macrolides including clarithromycin and amoxicillin (currently used for treatment of H.pylori) among the respiratory pathogens such as Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis.3 In deciding whether H.pylori should be eradicated for treatment of non ulcer dyspepsia, we urge the researchers to consider the impact of antibiotic treatment on microbial resistance both at individual and global levels. In sum, using antibiotics is like squeezing the balloon- you squeeze on one side, it pops out on another side. One has to think hard whether it is worth squeezing at all! References: 1.Adamsson I, Nord CE, Lundquist P, Sjostedt S, Edlund C. Comparative effects of omeprazole, amoxycillin plus metronidazole versus omeprazole, clarithromycin plus metronidazole on oral, gastric and intestinal microflora of Helicobacter pylori infected patients. J Antimicrob Chemother 1999; 44: 629-640 2.G Gopal Rao, J O'Donohue, C S Mahankali Rao, H Fidler, Treatment of Helicobacter pylori infection BMJ, Jun 2000; 320: 1540. (letter) 3.Hoban D, Felmingham D. The PROTEKT surveillance study: antimicrobial susceptibility of Haemophilus influenzae and Moraxella catarrhalis from community-acquired respiratory tract infections. J Antimicrob Chemother. 2002 Sep;50 Suppl S1:49-59 Competing interests: None declared |
|||
|
|
|||
|
Brian S. Alper, Editor-in-Chief www.DynamicMedical.com
Send response to journal:
|
This trial found a 3.3% absolute difference in the proportion of patients consulting primary care physicians for dyspepsia over 2 years following H. pylori eradication. There was a 2.3% absolute difference in the baseline rates of dyspepsia symptoms -- 24.3% of intervention patients and 26.6% fo placebo patients. This could account for much of the difference in the primary outcome. Could the authors provide subgroup analyses of results in patients with dyspepsia symptoms at baseline and for patients without dyspepsia symptoms at baseline? This might suggest whether the screening could be limited to symptomatic patients without reducing efficacy. Competing interests: None declared |
|||
|
|
|||
|
J Athene Lane, Research Fellow in Health Services Research Department of Social Medicine, University of Bristol Bristol, BS8 2PR, UK, Liam J Murray, Sian Noble, Matthias Egger, Ian M Harvey, Jenny L Donovan, Prakash Nair, Richard F Harvey
Send response to journal:
|
Editor We thank the correspondents who have responded to our paper (1) on population screening and treatment for Helicobacter pylori infection. They raise a number of interesting points. A screening and eradication programme in the community has, however, a very different aim from a ‘test and treat’ approach. Participants in a community study who already have H pylori-related symptoms will benefit from H pylori screening and eradication or a ‘test and treat’ programme (which only includes dyspeptic patients) equally, as they would in clinical practice [as described by Holland (2)], but in a community study potentially greater numbers will benefit by treatment prior to symptom development. The ‘test and treat’ subgroup analysis that Alper (3) proposed examining those participants with dyspepsia symptoms at baseline showed no difference in the consultation rate for dyspepsia two years following eradication therapy compared to the ITT analysis (odds ratio 0.69 95% CI 0.41 to 1.11). Duodenal ulcer symptoms can occur at any age in H pylori-infected individuals and in these the annual ulcer incidence is about 1 to 3/1000 people.(4,5) Population screening and eradication of H pylori in early adult life would prevent the later development of virtually all non-NSAID duodenal ulcers but only modest benefits would be observed by two years of follow-up. We agree with Ford and colleagues (6) that a longer follow-up may, therefore, show progressive savings in resource use and reductions in gastric cancer incidence. We concur with Rao (7) that the potential problems associated with a widespread use of antibiotics is a policy implication of a H pylori screening programme. Penston’s opinion that the Bristol Helicobacter Project is a ‘thinly disguised marketing ploy’ (8) echoes his views that large-scale randomised trials are vehicles whereby the ‘powerful vested interests’ of the pharmaceutical industry hope to gain ‘enormous profits to be made from the long-term treatment of chronic diseases’ (9). This study was jointly funded by the NHS R&D programme and GWUK with independent review prior to commissioning. The authors also retained full control over data collection, analysis and publication. When the study began in 1996 there was no randomised trial evidence on the impact of H pylori screening in the community or its role in conditions other than peptic ulcer. We wish to correct his factual errors: 1) Reductions in dyspepsia consultations and symptoms following H pylori
eradication are beneficial to patients.
J Athene Lane1
1Department of Social Medicine, University of Bristol, Bristol, UK.
References 1. Lane J A, Murray LJ, Noble S, Egger M, Harvey IM, Donovan JL, Nair P, Harvey RF. Impact of Helicobacter pylori eradication on dyspepsia, health resource use, and quality of life in the Bristol Helicobacter Project: randomised controlled trial. Br Med J 332: 199-204; 2006. 2. Holland DD Helicobacter pylori eradication. BMJ. Rapid response 25.1.2006. 3. Alper BS. Screening vs testing symptomatic patients. BMJ. Rapid response 5.2.2006 4. Doll R, Avery Jones F, Buckatzsch M. Occupational factors in the aetiology of gastric and duodenal ulcers. Spec Rep Ser Med Res Counc Lond No 276; 1951. 5. Harvey RF, Spence RW, Lane JA, Nair P, Murray LJ, Harvey IM, Donovan J. Relationship between the birth cohort pattern of Helicobacter pylori infection and the epidemiology of duodenal ulcer. QJM 95: 19-25; 2002. 6. Ford AC, Forman D, Bailey AG, Axon ATR, Moayyedi P. Population screening and treatment for Helicobacter pylori. BMJ. Rapid response 3.2.2006. 7. Rao GG. Squeezing the balloon. BMJ Rapid response 5.2.2006. 8. Penston J. A marketing ploy in the guise of clinical research? BMJ. Rapid response 4.2.2006. 9. Penston J. Large-scale randomised trials – a misguided approach to clinical research. Med Hypotheses 64: 651-7; 2005. 10. Peterson WL, Ciociola AA, Sykes DL, McSorley DJ, Webb DD. Ranitidine bismuth citrate plus clarithromycin is effective for healing duodenal ulcers, eradicating H. pylori and reducing ulcer recurrence. RBC H pylori Study Group. Aliment Pharmacol Ther 10: 251-261, 1996. 11. Axon AT, Ireland A, Smith MJ, Rooprams PD. Ranitidine bismuth citrate and clarithromycin twice daily in the eradication of Helicobacter pylori. Aliment Pharmacol Ther 11:81-87; 1997. 12. Moayyedi P, Feltbower R, Brown J, Mason S, Mason J, Nathan J, et al. Effect of population screening and treatment for Helicobacter pylori on dyspepsia and quality of life in the community: a randomised controlled trial. Leeds HELP Study Group. Lancet 2000;355:1665-1669. Competing interests JAL and RFH were funded to attend the AGA meeting in 2000 by GWUK. Competing interests: JAL and RFH were funded to attend the AGA meeting in 2000 by GWUK. |
|||
|
|
|||
|
Brian S. Alper, Editor-in-Chief www.DynamicMedical.com
Send response to journal:
|
Can you please provide the subgroup analysis for asymptomatic patients (patients without dyspepsia at baseline)? And for that subgroup, can you report the percentage who consulted for dyspepsia in primary care in in the intervention and control groups? Competing interests: None declared |
|||
|
|
|||
|
James Penston, Consultant Physician/Gastroenterologist Scunthorpe General Hospital, Cliff Gardens, Scunthorpe, North Lincolnshire DN15 7BH
Send response to journal:
|
Sir, Whilst I am, of course, grateful to Lane et al. [1] for drawing attention to the consistency of my views concerning large-scale randomised trials, [2] [3] there is little else in their letter with which I am in agreement. They clearly believe that their study [4] shows that eradication of H. pylori is beneficial to large groups of mostly asymptomatic individuals. However, if they set aside their pre-occupation with relative risk reductions and focus instead on the absolute difference between the treatment groups, they may realise that the apparent benefits are trivial. Indeed, there is increasing evidence to indicate that such small differences are regarded by patients – and, for that matter, by doctors and other health care professionals – as being insufficient to warrant treatment. With regard to the choice of eradication therapy, Lane et al.[1] ignore the fact that the only data for ranitidine bismuth citrate-based eradication regimens available when their study was designed were those relating to the extensive research programme leading up to the launch of Pylorid in 1995. By September 1995, it was known that the original analysis of the data from these trials was flawed and that the results in fact showed that ranitidine bismuth citrate-based eradication therapies were much less effective that other established regimens. As for the failure to use an intention-to-treat analysis for reporting the eradication rates and the high spontaneous clearance of H. pylori in the placebo group, the authors’ reply tends to support the conclusion that these problems would lead to a falsely inflated eradication rate. It is difficult to accept the claim that the results would not have been available for the promotion of ranitidine bismuth citrate. Had this drug been a marketing success, the Bristol study would surely have been widely disseminated in advertisements and promotional materials – moreover, the publication would probably not, as it turned out, have been delayed for five years after the completion of data collection. Was the Bristol study “a marketing ploy in the guise of clinical research”? [2] The authors have not argued their case against this proposition successfully. References [1] Lane JA, Egger M, Harvey IM, et al. The impact of H. pylori eradication on dyspepsia, health resource use and quality of life in the Bristol Helicobacter Project. Authors’ reply. BMJ, rapid response letters 24th February 2006. [2] Penston J. A marketing ploy in the guise of clinical research? BMJ rapid response letters, 4th February 2006. [3] Penston J. Large-scale randomised trials – a misguided approach to clinical research. Med Hypotheses 2005;64;651-7. [4] Lane JA, Noble S, Donovan JL, Murray LJ, Egger M, et al. Impact of Helicobacter pylori eradication on dyspepsia, health resource use, and quality of life in the Bristol helicobacter project: randomised controlled trial. BMJ 2006;332;199-202. Competing interests: None declared |
|||