Nepal develops more effective drug for typhoid

[Ramri]

thanks for this info and for the replies

[Rajiv]

I agree with Dr Pandit,
it is similar in Germany. They took Gati from market here only because of its dangerous effect "possibly" in combination with oral Anti-diabetica. Other significant complaints have not been registered.

[Pal]

Originally Posted by Anil Tuladhar

I am no way trying to belittle their hardwork and effort on this study and provide cheaper drug for one of the commonest infectious disease in Nepal. It is a superb paper as far as looking into the outcome measures.

Originally Posted by anilpandit

Being the first author of the article, I would end my discussion saying that I would take gatifloxacin if I get typhoid. I would treat my brothers, father and mother with gatifloxacin if they get typhoid and don't have diabetes.

Wow, it is a wonderful discussion, thanks to Anil Tuladhar for bringing this topic into the discussion. It gives an idea that a research is not just a research but it paves the way for the clinicial to change their path.

Thanks to Prof. Basnyat and Anil Pandit for clearify the issues associated with it.

[JNUS]

Rather, it was quoted as : "Please note that due to safety reasons this trial was terminated on the 8th September 2005."

1. What was the safety reason for which this study was prematurely terminated (though not mentioned in the original paper)? Please read following link: ISRCTN75784880 - An open randomised comparison of Gatifloxacin versus Cefixime for the treatment of uncomplicated enteric fever

As the article clearly states the trial was stopped because gati was found to be so effective in comparison to cefxime that the data safety monitoring board thought it was unethical to continue the trial based on priori defined numbers. This was not for safety reasons.

Originally Posted by Anilpandit - Trails are stopped early due to various reasons. One being if a drug is found to be very very effective than other compared drug. Then the trial is stopped in the middle because the difference in out come was so huge that you dont' need to reach the target sample size to have statistically significant results.

I hope the trial registration done by Dr Jeremy Farrar, Funded by The Wellcome Trust (UK) (grant ref: 061330), and Sponsored by University of Oxford (UK), is same with the study done by Dr Pandit. Finally making me confused regarding completion of study ? and no of target trials and study population ; termination of the trial ?


What was the trial Period ? Date of starting to end , Please !

The drug company pulled the drug out in the USA whilst the trial was going on

Can we use the medicine for study / practice that has not approved for therapeutic use in nepal, or is it approved in Nepal?

Nepal Pharmacy Council - If your concern is for GatiIfloxacin than I want to inform you that this drug not yet approved for therapeutic use in Nepal.

To : Dr. Pandit

I don't know why but i am eager to know whether this particular study is the Primary interest of the 1st author (Dr. Pandit) or the interest of Funding and Sponsoring Org. or interest of non-nepalese Foreign doctor involved in this study ?

I think you are too far now to treat nepalese population but what is the final effect of your study in Patan Hospital and You ???

Are Doctors Prescribing GatiIfloxacin in Patan for Typhoid Fever ?

Are you Prescribing GatiIfloxacin in Maryland , even for a single case of Typhoid Fever there ? If Not, are you ready to prescribe it for non-diabetic american out there ?

Being the first author of the article, I would end my discussion saying that I would take gatifloxacin if I get typhoid. I would treat my brothers, father and mother with gatifloxacin if they get typhoid and don't have diabetes.

To my little knowledge Study should be based on ethics, should be harmless to patient, should be aimed to result in benifit to medicine and also are pillars of it.

I am so much excited to know the application of the study for the benifit of mankind in Medicine ....?? What is being done and happening after this study?

Are we all ready to use it ?

Are we getting approval of it or already got one ?

Final Question being a young practicionar , Shall we start prescribing it or still long way to go ?

[rbineeta]

After reading the link mentioned in Dr Tuladhar's thread I can not but feel there is something authors of this paper have chosen not to disclose as to why trial was prematurely terminated for 'safety' reason. If Gati was too good then why do you say it was terminated for safety reason. Or does it imply that Cefixime is unsafe and it license should be withdrawn for use in Typhoid.
May be I am not as clever as these authors are that I can not get my head round this.

The unfortunate gentleman who died in cefixime group entered in trial after 10 days of illness !!! One can argue that the outcome would not have been different even if he was in the Gati group.

I want to ask Oxford Reasearch Council -- How did they find it ethical to approve study of a drug which is not licensed in the UK was withdrawn from the European market.

Finally, Dr Pandit just because you were the first author and hence prepared to take Gati if you get ( God forbid) typhoid in Maryland does not mean that poor defenseless Nepalese should be exposed to its risks. Sometimes KAG REALLY TAKES KAN AWAY

[Pal]

Questions raises in the few last posts are noteworthy.. but as far as I learned that.

1. Study was prematurely terminated becasue the result was too good i.e. Gati looked good as compare to cefi - there is no use of continuing research - so lets not raise the same question as authors have already answered this questions.

2. The biggest question is yes... is Gati is being used in the Patan or Nepal or not..... if yes than research achieved its goal if not then I think the last point Anil Pandita has said is too biased towards his research

Originally Posted by Anil Pandit

I would treat my brothers, father and mother with gatifloxacin if they get typhoid and don't have diabetes.

Dr. Pandit, the intensity you showed by saying above word shows that you have done preety good in your part but don't you think its looks to bias "Mero goru ko barahai takka".

Hey please don't take it otherwise, its a academic discussion and I am not the one to say its right or its wrong the point is - was it academically sound or not.

Hundreds of research paper published in Nepalese Medical Journal and other biomedical journal but your research has got the attention its good for the author.

I read the PLOS One website and it says that....

PLoS ONE is now welcoming submission of papers reporting results of all types of clinical trials, irrespective of outcome. [Link] I think this mean they don't bother about the outcome of the research they will just publish the article no matters what it come up with except it is scientifically done and written as they have said that "PLoS ONE aims to publish all research that is ethically conducted, technically sound and properly described." [Link] further it says "PLoS Clinical Trials aims to broaden the scope of clinical trials reporting by publishing the results of all correctly conducted clinical trials, regardless of the direction of results, size or perceived importance of the trial."

It is mention in ths link - PLoS Clinical Trials : A Peer-reviewed, Open-access Journal - Journal that

PLoS Clinical Trials will be moving to the PLoS ONE publishing platform. PLoS ONE is now welcoming submission of papers reporting results of all types of clinical trials, irrespective of outcome.

By going through above words in the PLoS One website I think gati result will not change the way clinician are treating for typhoid.

Another similar study need to support it or refute it, because a single research can not can not say that this one is right.

Above all, the intention of the authors were awesome that they wanted to introduce cheaper but effective drug for typhoid, that is appreciable.

[Anil Tuladhar]

I am very glad to see so much of discussion around this topic and interest so generated by this on everyone concerned and this is how it should be. This does help in dissemination and sharing of our knowledge.

But I am deeply saddened by some of the quotes and comments from the authors. Those comments are unwarranted, unasked for and not expected from a responsible medical professional. Here, we are trying to have a healthy debate. In any research, there is always bound to be questions asked on different aspects of the study and it is the duty of the researchers to convince readers or answer the questions correctly and appropriately. This may or may not convince the individuals and it is up to the individuals to rate the study on that ground. This is what happens worldwide. The response from one of the authors is like that of someone immature who has never been criticised, never could take criticism and reflect on it nor has humility to respond and clarify the queries politely.

I was drawing attention at the side effect of Gatifloxacin, the very reason this drug came to disrepute and was given “Black Label” by USA Food and Drug Administration Agency. The investigators have ignored to look for this side effect. Have they proven that dysglycaemia is not a problem in this study; I believe the results would have been more robust. The authors tried in their defence of omitting blood sugar level by quoting another study involving children. If this study is a full description of all the safety data available, then this appears to have occurred without new data demonstrating real rather than imagined concerns about the safety of Gatifloxacin. The safety data in this study is hardly enough to conclude that Gatifloxacin is safe.

References:
Pichichero ME, Arguedas A, Dagan R, Sher L, Saez-Lorens X, et al. (2005) Safety and efficacy of gatifloxacin therapy for children with recurrent acute otitis media (AOM) and/or AOM treatment failure. Clin Infect Dis 41: 470–478.

Merchant CD. (2005) Gatifloxacin Therapy for Children: An Antibiotic Still in the "Back Room" Clin Infect Dis 41: 479-480.

The analogy of side effects of Gatifloxacin and other fluoroquinolones seemed inconceivable. We still wait to see a drug which doesn’t have any side effect. But one cannot put price on the cost of life, which we are debating in case of Gatifloxacin and compare it with any side effects leading to morbidity (like cartilage toxicity of other fluoroquinolones).

If my conviction, based on available evidence but not on experience only,tells me to encourage or discourage my patients to use or stop taking the drug, I would do so irrespective of who they are (my near or dear ones or anyone of any race, religion, caste or nationality) as expected of any medical professional.

It is quite interesting to see that there are five authors based in the UK, where Gatifloxacin is not licensed, with ethical approval for this study granted by Oxford Tropical Research Ethics Committee. I just wonder whether they would have received ethical approval to conduct any study involving Gatifloxacin in the UK. They might but not in million years on the current available evidence.

However, this paper is a very good example in demonstrating why we need to screen through all 10 points in the appraisal tool while reading an article (Refer “How to critically appraise an article?” on sticky section of Journal Club forum in the xenoMED forum).

[Anil Tuladhar]

Priori means designating the process of reasoning without reference to any particular facts or experience.

In every trial a statistical point is defined which if reached before the targetted number of recruits, the study could be discontinued. In this study they defined p<0.01 as the point if reached either way, they would terminate the study. I hope I explained what "priori defined" means.

Originally Posted by Ajay

I didnt get

Could anyone clearify this, please?

[khusidr]

here is the original article,
Click to download, in PDF format

[TIME]

Thanks to everyon who have involved in this discussion.

I learnt many aspect of research, I beleive that everyone of us who went through this discussion have benefitted a lot.