Questions are being raised across the world on a new research article of Tata Memorial Hospital (TMH). It has been claimed in this article that pills containing papaya leaf extract help in increasing platelet count in patients undergoing chemotherapy.
‘Journal of Global Oncology’ – a peer-reviewed medical journal had published TMH’s paper a few days ago. Now investigating this study. Kochi-based hepatologist Dr Cyriac AB Phillips is famous as ‘The Liver Doc’ on social media. He is known for exposing pseudoscience, and requested the journal to conduct an internal review.
A disclaimer has now been added to the online version of the research paper. It says that the journal has been informed about some concerns regarding the results and clinical interpretation of the points mentioned in this article and this is currently under investigation. Readers should interpret this carefully.
Study started with 219 patients
The study started with 219 patients, but after removing some people, researchers reduced the final number to 198, including 69 people in the placebo group. They ultimately concluded that although long-term follow-up is needed, their results suggest that these pills could be an inexpensive treatment for chemotherapy-induced thrombocytopenia (low platelet count) and could help maintain the intensity of chemotherapy.
Objection to reducing the number of patients during research
Dr. Phillips has objected to this very thing. He said that in the group taking papaya pills, researchers removed patients who did not recover before drawing final results. He explained that you can see that the number of recovered patients has remained at 83, while the total number (the total number of people included in the study) has decreased from 146 to 129.
Dr. Phillips added that by simply removing the unsuccessful cases and keeping the successful cases as they were, the researchers actually increased the recovery rate of the papaya extract from about 57% to about 64% without recovering a single additional patient. Additionally, they reported that even in the placebo group, some patients who recovered were excluded from the final analysis.
Claim of experts who did the study
Dr. Vikas Ostwal, the lead author of the study, said that the journal has asked us some questions, which we are currently answering as per the standard protocol. We are confident in our research. Our patients have been receiving papaya extract tablets, and have seen a steady increase in their platelet counts by the fourth day (maybe a day or so). The medicines for the trial were provided by ‘Micro Labs Pvt Ltd’ and the study received external grants from ‘Zydus Pharma Pvt Ltd’ and ‘Lupine Pharma Pvt Ltd’. Lupine Pharma itself sells tablets containing this extract under the brand name ‘Caripapa’. Dr. Ostwal said that although the researchers were aware of the sources of funding, none of them – not even himself – knew that one of the funders’ companies sold the pills.
Dr. Phillips expressed concern
Dr. Phillips also expressed concern that the primary endpoint of the study was changed from day 7 to day 4. The main goal of the trial should be decided before the results are analyzed. He said that the main goal in the original registration and protocol was ‘platelet recovery by day 7’, but data from day 4 was used instead. Whereas the data of the fourth day was only for mid-way testing.
Question on credibility of study
A retired biostatistician from a public health institute also agreed, saying that changing the main objective after the analysis and excluding some people from both groups is a red flag, which reduces the credibility of the study. Doctors may have seen a clinical benefit and tried to fit it into the data, but on paper there is certainly a problem.
Dr Amar Jesani, one of the founders of the ‘Indian Journal of Medical Ethics’ and former member of the Ethics Committee of Tata Hospital, said there can always be differences of opinion. Science cannot exist without conflict. What is not acceptable is work done without a scientific methodology. This is what has to be proved in this case. One way forward is for Tata Memorial Hospital to release the raw and de-identified data into the public domain. Experts say that although the journal’s investigation will be important, a new clinical trial will help prove or disprove the results.