madhu sasidharan

i am a doctor specialised in gastroenterology

[Dr. Narendranathan @drm_narendran]

CLINICAL TRIAL WITH PLACEBOS IN SMALL INTESTINAL ANGIODYSPLASIA
-TUSKEGEE, REVISITED?
This post is about a clinical trial conducted on small intestinal angiodysplasias (SIA) and published in the New England Journal of Medicine (Reference 1). The study proved the efficacy of thalidomide as a treatment option in SIA. In this clinical trial fifty patients with SIA received a placebo and one hundred patients received thalidomide. The 100mg thalidomide group demonstrated a response rate of 68%, whereas the placebo group exhibited a response rate of only 16%. This was not surprising as the same group of investigators have showed the superiority of thalidomide over placebo in a study done 12 years earlier (Reference 2). The NEJM study was a replicated placebo- controlled study. To quote the authors:
“In our previously reported trial, the percentage of patients with an effective response was 71.4% in the 100-mg thalidomide group and 3.7% in the iron control group…. Thalidomide is an effective and relatively safe treatment for patients with refractory bleeding from gastrointestinal vascular malformations.”
It is widely recognized that untreated SIA can lead to morbidity and even mortality. However, in the replicated study thalidomide (proved to be effective in SIA by the same investigators) was withheld from fifty participants with the SIA and instead, placebos were administered. Is this ethical? The initial study, as per existing guidelines, is ethical. The second study done after establishing the effectiveness of the study drug violates standard ethics guidelines as fifty participants with a serious disease were denied effective treatment and were administered placebos. When this was pointed out, the response from the editor of NEJM was that “thalidomide had not been established as standard of care.” It was obvious that the justification of the duplicated placebo-controlled trial came without reviewing the literature. In my professional opinion, it is concerning that a journal committed to upholding the principles of bioethics had published this article. Do persons, who justify a clinical trial with placebos in SIA have any right to criticize the Tuskegee study (Reference 3), where the treatment was withheld from persons with syphilis?
This write up is to point out the ethics of duplicating a placebo-controlled study. It is imperative that this issue is thoroughly examined, and the ethical issues are brought to the forefront to ensure that similar studies are not repeated, and researchers are cognizant of the ethical breaches. Measures must be implemented to prevent such studies from evading the oversight of institutional review boards and journal reviewers. The ethical implications of replicating a placebo-controlled study have not been thoroughly examined in the current body of literature on ethics in human research.
I eagerly look forward to the response of the readers of this write up.
References:
1. Chen H et al: Thalidomide for recurrent bleeding due to small-intestinal angiodysplasia. New England Journal of Medicine. 2023;389(18):1649-59.
2. Ge ZZ et al: Efficacy of thalidomide for refractory gastrointestinal bleeding from vascular malformation. Gastroenterology. 2011;141(5):1629-37.
3. Curran WJ. The Tuskegee syphilis study. New England Journal of Medicine. 4;289(14):730-1.

Dr. M. Narendranathan. MD., DM,. MPH

[madhu sasidharan @drmadhus]

@ntaofficialinn it's a shame where NTA conducts a farce exam where even the first 86 ranks are decided by lucky dip 😡

[madhu sasidharan @drmadhus]

@ntaofficialinn it is ridiculous to conduct an exam where the first rank up to rank 86 is decided by lucky dip.#shameful. I guess NTA is not at all concerned about the quality of education in health care 😡

[madhu sasidharan @drmadhus]

@AshwiniVaishnaw railways cancelled train booking under PNR 4163369315. Now refusing to refund my money saying technicality of not notifying them within 72hr when railways let's me know the train is cancelled when I reach the railway station at midnight with my family ! Help 🙏

[madhu sasidharan @drmadhus]

The most horrible coaches in any rajadhani express imaginable in put on the trivandrum Nizamudeen rajadhani! @ShashiTharoor

[madhu sasidharan @drmadhus]

@MKBHD Give me one of those

[madhu sasidharan @drmadhus]

Help me win an iPhone 12 for free! https://t.co/lF7DXJGKDX

[madhu sasidharan @drmadhus]

Help me win an iPhone 12 for free! https://t.co/lF7DXJGKDX

[madhu sasidharan @drmadhus]

@nsitharaman going on increasing taxes is the stupidest thing to do. Petrol taxes @70% ridiculously pathetic

[madhu sasidharan @drmadhus]

@realpreityzinta Hi

[madhu sasidharan @drmadhus]

@narendramodi Please do something to ensure quality in medical education and ensure good medical facilities in public sector

[madhu sasidharan @drmadhus]

At IMG word Dubai

[madhu sasidharan @drmadhus]

@SushmaSwaraj madam please look in to reducing the visa fee for medical tourism

[madhu sasidharan @drmadhus]

@sureshprabhu travelling by train 16525 in first AC sleeper. Pathetic condition of toilets

[madhu sasidharan @drmadhus]

@realpreityzinta hi preity

[madhu sasidharan @drmadhus]

@realpreityzinta hi preity

[madhu sasidharan @drmadhus]

@karanjohar my daughter is 9 yrs old and big fan of yours she wants to write a letter to you.please do reply

[madhu sasidharan @drmadhus]

@realpreityzinta why up so late are you not in India thanks for the response

[madhu sasidharan @drmadhus]

@realpreityzinta hi zinta

[madhu sasidharan @drmadhus]

@realpreityzinta hi preity