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Year : 2011  |  Volume : 2  |  Issue : 1  |  Page : 42-43  

Clinical trials with poor methodological quality and inappropriate statistics: Are they ethical?

1 Department of Pharmacology, Govt. Medical College, Surat, Gujarat, India
2 Department of Community Medicine, Govt. Medical College, Surat, Gujarat, India

Date of Web Publication15-Jul-2011

Correspondence Address:
Department of Pharmacology, Govt. Medical College, Surat, Gujarat
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0976-9234.82979

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How to cite this article:
Jaykaran, Saxena D. Clinical trials with poor methodological quality and inappropriate statistics: Are they ethical?. J Pharm Negative Results 2011;2:42-3

How to cite this URL:
Jaykaran, Saxena D. Clinical trials with poor methodological quality and inappropriate statistics: Are they ethical?. J Pharm Negative Results [serial online] 2011 [cited 2020 Jul 7];2:42-3. Available from:


Clinical trials are considered as gold standard for analyzing the efficacy of new intervention. India is becoming a hub of clinical trials. [1] Many ethical concerns were raised for the clinical trials taking place in India. [2],[3] Many efforts are taken for improving the ethics of clinical trials, and one of the important steps is registry of clinical trials. [4] Editors of 12 prominent biomedical journals of India came together to announce that after Jan 2010, they will consider publication of only those clinical trials that are registered in the Clinical Trial Registry. [5] For any clinical study and, particularly clinical trial, the two important ethical parameters are: written informed consent from the participants and permission from the Institutional ethics committee. Lot of stress is given for these components in various surveys carried out for assessing the ethical reporting in the published literature. One component that is usually ignored is the methodological and statistical aspect of clinical trials. Many clinical trials published in biomedical journals are poor in methodological aspects, including statistical analysis. Not only are these clinical trials underpowered but other statistical parameters like missing data analysis, adjustment of multiple endpoints, etc. are also not reported adequately in the published literature. [6],[7],[8],[9],[10]

Clinical trials based on poor methodology and inappropriate statistical analysis cannot give a valid conclusion of research hypothesis. Therefore, data obtained by these kinds of clinical trials are "scientifically useless." [11] These faulty studies raise some important ethical issues, like - is exposure of patient to new intervention and depriving him from normal acceptable intervention justified for the study which cannot answer the hypothesis with certainty? Is it not the wasting of time and resources? Are the clinical judgments based on results of these clinical trials reliable? [12],[13] These questions are ethically very important but seem to be ignored. During the recruitment of subjects in clinical trials, it is the duty of the investigator to provide all relevant information to the participants regarding the clinical trial, including the implications of results obtained in that trial. If power analysis is not performed, then it is the duty of the investigator to inform the subjects about the limited value of the study so that they can decide whether to participate or not. Failure to share this information can also be considered as unethical. [6] The investigator may fear that sharing this information may decrease the recruitment. But, the subjects who come to get randomized in clinical trials for a noble cause have all the rights to participate in adequately powered clinical trials. [6] If the clinical trial is underpowered but has sound methodological parameters, including statistics, then the data generated in that trial can be utilized for metaanalysis and also to get an idea about the efficacy through CI. [6],[14] But, the same cannot be done with the clinical trials with poor methodological qualities, like absence of missing data analysis, no adjustment of multiple endpoints, etc. or in case of clinical trials in which inappropriate statistical tests are used for the analysis of data.

There may be various reasons for occurrence of these errors. Insufficient knowledge of the investigator about the research methodology and statistics is one important reason. Many clinical trials are conducted without involving the statistician at the design phase of the trial. [15],[16] Insufficient review of the protocol by the Institutional ethics committee and inadequate peer reviewing of the manuscript may also contribute to these errors in published articles.

The ethics committee's role is very important. Ethics should not be taken in a narrow sense and confined to informed consent. It is very important to understand that poor research is also unethical. Help from a medical statistician should be taken during reviewing of protocols. The ethics committee members should carefully read the consent form to see whether adequate information regarding the strength and limitations is going to be given to the participants or not. The ethics committee should also discuss the methodological and statistical aspects of clinical trials. Issues like statistical tests to be used for analysis, method to be used for adjustment of multiple endpoints, calculation of sample size, etc. should be asked to the investigators.

The journal editor's and peer reviewer's role is also important. All the clinical trials should be sent for statistical review before formal peer review. It is observed that still many journals do not have statisticians in their editorial board. [17] Medical statisticians should be a part of the editorial board of the journal. With the published article, a link can be provided where raw data of the study could be found so that a knowledgeable reader can apply the same statistical method as that applied by the authors and can see its replicability. Peer reviewers of journals should be trained in statistical methods. Journal editors should encourage publication of "letter to editors" for the published manuscripts so that any methodological and statistical fault present in the published manuscript that remained in peer reviewing can be discussed.

   References Top

1.Borfitz D. Lifting India's barriers to clinical trials. Center Watch 2003;10:1-9.  Back to cited text no. 1
2.Jayaraman KS. Outsourcing clinical trials to India rash and risky, critics warn. Nat Med 2004;10:440.  Back to cited text no. 2
3.Mudur G. Johns Hopkins admits scientist used Indian patients as guinea pigs. Br Med J 2001;323:1204.  Back to cited text no. 3
4.Tharyan P. Ethics committees and clinical trials registration in India: Opportunities, obligations, challenges and solutions. Indian J Med Ethics 2007;4:4none .  Back to cited text no. 4
5.Satyanarayana K, Sharma A, Ganguly NK. Indian registry for clinical trials. Indian J Med Res 2006;123:587-90.  Back to cited text no. 5
[PUBMED]  Medknow Journal  
6.Halpern SD, Karlawish JH, Berlin JA. The continuing unethical conduct of underpowered clinical trials. JAMA 2002;288:358-62.  Back to cited text no. 6
7.Karan J, Kantharia ND, Yadav P, Bhardwaj P. Reporting statistics in clinical trials published in Indian journals: A survey. Pak J Med Sci 2010;26:212-6.  Back to cited text no. 7
8.Saurabh MK, Jaykaran, Yadav P, Chavda N, Lokesh RV, Deodhare S, et al. Reporting of missing data in clinical trials published in four Indian journals: A survey. J Pharma Res 2010;3:277-9.  Back to cited text no. 8
9.Jaykaran, Saurabh MK, Gohiya S, Gohiya V, Sharma G, Chavda N. Reporting of Power, Sample Size and Confidence interval in negative clinical trials published in four Indian medical journals. J Pharma Res 2010;3:298-300.  Back to cited text no. 9
10.Jaykaran, Gohiya S, Gohiya V, Sharma G, Saurabh MK, Yadav P. Reporting of the methodological quality and ethical aspects in clinical trials published in Indian journals: A survey. J Pharma Res 2010;3:307-9.  Back to cited text no. 10
11.Altman DG. Statistics and ethics in medical research III: How large a sample? BMJ 1980;281:1336-8.  Back to cited text no. 11
12.Altman DG. Statistics and ethics in medical research: Misuse of statistics is unethical. BMJ 1980;281:1267-9.  Back to cited text no. 12
13.Altman DG. The scandal of poor medical research. BMJ 1994;308:283-4.  Back to cited text no. 13
14.Edwards SJL, Lilford RJ, Braunholtz D, Jackson J. Why "underpowered" trials are not necessarily unethical. Lancet 1997;350:804-7.  Back to cited text no. 14
15.Jaykaran, Chavda N, Yadav P. Proper reporting of statistical parameters in clinical trials published in Indian medical journals: Is inclusion of statistician play any significant role? J Young Pharma 2011;in press.  Back to cited text no. 15
16.Altman DG, Goodman SN, Schroter S. How statistical expertise is used in medical research. JAMA 2002;287:2817-20.  Back to cited text no. 16
17.Goodman SN, Altman DG, George SL. Statistical reviewing policies of medical journals: Caveat lector? J Gen Intern Med 1998;13:753-6.  Back to cited text no. 17

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