Analysis of Clinical Trials in Children Registered in the

Clinical Trials Registry of India

S. Manikandan*, M. Jayanthi*, B. Gitanjali**

and G. Sivagnanam* *Indira Gandhi Medical College & Research Institute, Pondicherry, India;

** WHO-SEARO, New Delhi

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Introduction

World Health Organization (WHO) established International Clinical Trials Registry Platform (ICTRP) in 2005

20 items are listed as Trial Registration Data Set (TRDS) which is the minimum amount of information necessary for a given trial to be considered fully registered.

India launched ‘Clinical Trials Registry-India’ (CTRI) in July 2007 to enhance transparency and accountability of trial reporting from India.

The quality of information in the registry should be good in order to satisfy the three main stakeholders, i.e., health care professionals, policy makers and trial participants.

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Introduction

1. Srivastava JS. Need for ethical oversight of clinical trials in India. Curr Sci. 2010;99:1505-7.

2. Moja LP et al. Compliance of clinical trial registries with the World Health Organization minimum data set: a survey. Trials. 2009;10:52.

Concerns about the conduct of clinical trials in India are growing.1

Information provided in the trial registries is insufficient and not current; hence benefits of registries are undermined.2

Paediatric trials are scarce due to difficulties involved in conducting them.

The need for ethical oversight of trials in India has been emphasized.1

Hence the information in registries gains more significance with reference to trials in children.

Objectives

To critically analyze the information on paediatric clinical

trials in Clinical Trials Registry – India (CTRI) in terms of:

information - completeness, transparency, currency and

compliance with WHO’s International Clinical Trial Registry

Platform (ICTRP) data set, i.e., Trial Registration Data Set

(TRDS).

To suggest measures to improve the quality of CTRI.

4http://www.ctri.nic.in

Methods

A cross-sectional study of paediatric clinical trials registered in CTRI.

Clinical trials in children < 18 years retrieved (as on 15 Aug 2010) by the keyword ‘children’ from CTRI website.

Two independent observers scored the response for each item, which was verified by a third person.

Method of scoring was defined a priori. The completeness of reporting, appropriateness and degree

of compliance of CTRI data with WHO- ICTRP items (WHO items) and CTRI-specific items were analyzed. 

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88 trials retrieved

7 adult studies

81 trials analyzed

Results

Completeness of Information 20 (25%) trials were completed; only 2 provided

the results; 2 provided conclusions .Fax number and affiliation of the Principal

Investigator were not given in ~ 90% of trials.Many participant countries have been left out.Duration and frequency of drug administration

was missing in 27% of trials.6

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Incomplete information - A few examples

Name of Institute ?

Reproduced from CTRI. Comments of authors are in red.

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Incomplete information - a few examples

??

Placebo has same constituents as test

drug

Reproduced from CTRI. Comments of authors are in red.

ResultsTransparency of information 3 (4%) trials have not disclosed the sources of

monetary & material support.41 trials needed regulatory approval, but only 32

have obtained it. Inconsistencies in the no. of sites, blinding etc.

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Reproduced from CTRI. Comments of authors are in red.

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CTRI No.Source undisclosed

Type Name

2009/091/000750

Pharma Co. GSK

2009/091/001059

Research Foundation

FABB, Italy

2010/091/000177

Pharma Co. Zydus, Roche

Lack of transparency - examples

Reproduced from CTRI.

Comments of authors are in

red.

Results

Currency of information 31 (38%) trials were updated after registration

whereas 7(9%) were not.Remaining 43 (53%), the date of last update is

prior to the date of registration.

11Reproduced from CTRI.

Comments of authors are in red.

Results

Compliance with WHO items (n=20) in CTRI

Compliance %

No. of items Items

100 6Trial No; Registration date; Secondary Sponsor; Scientific Title; Health condition; Recruitment status

80-99 8

Support source; Primary Sponsor; Study -Type; Countries; first enrollment date; sample size; outcome – Primary, secondary

60-79 3Public Title; Secondary Identifying No; Inclusion & Exclusion Criteria

<60 3 Contact -public query; Scientific query; Intervention

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Results

Compliance with CTRI-specific items (n=13)

Compliance %

No. of items Items

100 3 CTRI No. & Date; Contact details; No. of sites

80-99 6

Site details; ethics committee approval; random sequence generation; blinding and masking; phase of trial; estimated duration of trial

60-79 1 Regulatory approval

<60 3 Principal investigator’s details; allocation concealment; summary

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ResultsUnethical use of placebo in registered trials

Health condition studied Reason to state use of placebo is unethical

Bronchial asthma Standard drug (bronchodilator) not used as comparator

Bipolar depression Placebo for 8 weeks instead of standard therapy (antidepressants)

Mild to moderate iron deficiency anemia

Placebo (unfortified rice) for 7 months without iron therapy

Rotaviral/ cryptosporidial gastroenteritis

Only probiotic (test drug) / placebo used. Rehydration with ORS not given

Active ulcerative colitis Placebo for 10 weeks, when disease process is active

Acute migraine Placebo instead of an analgesic in acute migraine14

Discussion

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Though the quantum of compliance is satisfactory in CTRI, the quality is found wanting.

Suggestions to improve CTRI Regular reminder to the registrants to update results and

information on completion of trial. Errors in the date of update can be rectified through

changes in the software. Ethical issues like the inappropriate use of a placebo

should be taken up with the principal investigators before registering the trial.

Summary of the clinical trials should be in English as well as vernacular – to help participants.

Separate link to be provided for children’s trials.

Conclusion

The information on children’s clinical trials in the CTRI is incomplete, not current, not regularly updated, and at times misleading.

The use of placebo is not justified in one third of the placebo-controlled trials in children.

The quality of information in CTRI may be improved by modifying the registry and making it user friendly and by providing assistance for registration.

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