Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 9  |  Issue : 1  |  Page : 31-35

Brief technical guide for registration of an observational study protocol


1 Department of Physiology, Santiniketan Medical College, Bolpur, West Bengal, India
2 Department of Physiology, Raiganj Government Medical College and Hospital, Raiganj, West Bengal, India
3 Department of Physiology, Hi-Tech Medical College and Hospital, Bhubaneswar, Odisha, India

Date of Submission01-Aug-2021
Date of Acceptance05-Aug-2021
Date of Web Publication23-Mar-2022

Correspondence Address:
Himel Mondal
Department of Physiology, Santiniketan Medical College, Bolpur, West Bengal
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijves.ijves_87_21

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  Abstract 


Background: Clinical trial registration is a must for the conduct of an interventional study. The registration should be in the repositories accepted by World Health Organization (WHO) and endorsed by the International Committee of Medical Journal Editors (ICMJE). These registries allow the registration of both interventional and observational studies. However, the majority of the observational studies are not registered. Aims: We aimed to find the current share of observational studies in various registries and to provide a brief technical guide on the process of registration of an observational study in the Clinical Trials Registry – India (CTRI) and in the open science framework (OSF). Methods: We searched the WHO and ICMJE websites for the list of accepted registries. The number of interventional and observational studies in those registries was collected. Then, we described the process of registration of an observational study in CTRI and OSF. Results: The highest number (83,866) of observational studies is present in ClinicalTrials.gov. However, according to percentage, the DRKS - German Clinical Trials Register has the highest percentage (31.57%) of observational studies. The CTRI has 25.33% and ClinicalTrials.gov has 21.91% observational studies. The registration of an observational study protocol is acceptable online and free of cost in the CTRI and OSF. Conclusion: It is not mandatory to register purely observational studies. However, the registration may bring transparency in scientific reporting and help to avoid publication bias towards positive results. The technical glimpse in this article would help the novice authors in registering their observational study protocol in an open repository.

Keywords: Clinical trial, India, observational study, publication bias, registries, research


How to cite this article:
Mondal H, Mondal S, Mahapatra AK. Brief technical guide for registration of an observational study protocol. Indian J Vasc Endovasc Surg 2022;9:31-5

How to cite this URL:
Mondal H, Mondal S, Mahapatra AK. Brief technical guide for registration of an observational study protocol. Indian J Vasc Endovasc Surg [serial online] 2022 [cited 2022 May 28];9:31-5. Available from: https://www.indjvascsurg.org/text.asp?2022/9/1/31/340512




  Introduction Top


Registration of interventional research or clinical trial is mandatory for the publication. The majority of the journals only accept the clinical trials that have preregistration in accepted databases. The World Health Organization (WHO) maintains a list of “primary registries” for trials that are also endorsed by the International Committee of Medical Journal Editors (ICMJE). The list can be obtained from the WHO or ICMJE websites.[1],[2]

Clinical trials are defined as “any research study that prospectively assigns human participants or groups of humans to one or more health-related interventions to evaluate the effects on health outcomes.” Any study that comes under this definition needs a preregistration. ICMJE further suggests that “purely observational studies in which the assignment of the medical intervention is not at the discretion of the investigator” do not require registration.[2] However, observational studies are important for the progress of evidence-based medicine. If preregistration aims to reduce publication bias, maintain a high ethical standard, reduce redundant research, and maintain a permanent public record, observational studies, even if it is purely observational, are also a candidate for preregistration.[3] In an editorial published in 2010, The Lancet expressed their interest to receive observational studies with a registered protocol.[4] Although experienced researchers are well aware of the process of registering an observational study, it is rarely discussed among novice researcher peers.

With this background, we would like to explore the current status of registration of observational studies in various registries and to provide a brief technical guide for authors who would like to register their observational studies.


  Methods Top


This study involves an audit of registries available in the public domain. We used our personal computers and internet connection for browsing the websites. The audit was carried out on July 25, 2021 from 11 a.m. to 12:30 p.m. As this study does not involve any human participants, permission from the Institutional Ethics Committee (IEC) was not necessary.

We searched observational studies and interventional studies in the registries found in the WHO and ICMJE. Some of the registries do not provide details about the category of the studies and some are not in the English language. Hence, those were excluded from the analysis.

Below are brief guidelines for registration of a study, be it interventional or observational in CTRI and open science framework (OSF). The OSF can be used for registering a study that does not need or is exempted from permission from the IEC.

Registration of a study in Clinical Trials Registry – India

The registration of studies in http://ctri.nic.in is provided free of cost to the user. A brief guide is presented in [Figure 1]. The user needs to register [Figure 1]a for the first time. During the registration [Figure 1]b, a segment of the form requires details of a verifier [Figure 1]c. Provide the name of a registered user of the portal or a mentor in your institution with all the details and submit the registration form [Figure 1]c. After confirming your registration link sent on the E-mail, you can log in to the portal. After logging in, the dashboard shows the summary and an option to add a new trial [Figure 1]d. Provide all the details and keep going [Figure 1]e to finally submit the protocol.[5]
Figure 1: Process of registering a study in Clinical Trials Registry – India (a) register as a new applicant, (b) provide personal details, (c) provide verifier's details, (d) after login, on the dashboard, click on “add new trial,” (e) provide details of the study protocol and proceed for a detailed form for entering data

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Registration of a study in open science framework

Here we briefly explain how a study, be it Ethics Committee approved or exempted, can be registered on OSF. The web portal, like all other trial registries, is free for users. You need to open an account at https://osf.io/ [Figure 2]a.[6] After logging in, on the dashboard click on the “Create new project” to start registering a new project [Figure 2]b. Fill up the title, storage (default is the USA), and description, click on “Create” [Figure 2]c. Provide details about the project such as hypothesis, study type, study design, blinding (if any), randomization (if any), data collection, sample size, the rationale of sample size, variables, analysis plan, inference, etc. From the contributors tab, you may add contributors to the project [Figure 2]d. If there is an error in data input, you may delete the project without hassle [Figure 2]e. After final input, make the project public [Figure 2]f to generate a permanent digital object identifier (DOI) [Figure 2]g for the registration. In addition, there is an option to add the license type [Figure 2]g. The DOI or a permanent web link can be shared with the manuscript when the paper is sent to journals [Figure 2]h.
Figure 2: Process of registering a project or study in open science framework – (a) signup with personal details, (b) on the dashboard, click on “create new project,” (c) provide title, storage location, and description and click on “create,” (d) from “contributors” tab, a new contributor can be added, (e) an option to delete the project is also there, (f) for generating DOI, make the project public and (g) click on “create DOI,” license can also be added from here, (h) en example of DOI and permanent weblink of a registered project. DOI: Digital object identifier

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Calculation and statistical analysis

The percentages were calculated with interventional and observational studies only. In a registry, if observational studies are X, and interventional studies are Y, then the percentage of observational studies is = (X/[X + Y]) ×100. The categorical data were analyzed statistically by the Binomial test where a significant P < 0.05 indicates that the distribution did not happen due to chances. We used GraphPad Prism 6.01 (San Diego, CA, USA) for the statistical analysis.


  Results Top


A report in 2013 showed that observational studies in ClinicalTrials.gov comprised 19% (27,666/148,607) of the total records.[7] The number of interventional studies and observational studies in Clinical Trials Registry – India (CTRI), ClinicalTrials.gov, and four other databases is shown in [Figure 3]. According to the number of registries, the highest number (83,866) of observational studies is in ClinicalTrials.gov. However, according to percentage, the DRKS - German Clinical Trials Register has the highest percentage (31.57%) of observational studies. Indian CTRI has 25.33% and ClinicalTrials.gov has 21.91% observational studies. All the registries have significantly (statistical significance in Binomial test) higher number of interventional studies. In comparison with the 2013 data of ClinicalTrials.gov, there was an increment of 101.09% in clinical trial registration and a 203.14% increment of observational studies in ClinicalTrials.gov.
Figure 3: Interventional and observational studies in various registries. CTRI: Clinical Trials Registry – India, CTUSA: U. S. National Library of Medicine ClinicalTrials.gov, ANZCTR: Australian New Zealand Clinical Trails Registry, CHICTR: Chinese Clinical Trial Registry, UMIN: UMIN Clinical Trials Registry, Japan, DRKS: Deutsches Register Klinischer Studien - German Clinical Trials Register. Data collected on July 25, 2021 from 11 am to 12:30 pm

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The registration of an observational study protocol is acceptable online and free of cost in the CTRI and OSF. Some of the frequently asked questions about CTRI and OSF are presented in [Table 1].
Table 1: Some of the frequently asked questions about Clinical Trials Registry - India and open science framework

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  Discussion Top


Current status of registered observational studies

The percentage of observational studies in six registries ranges from 12.64% (in Australian New Zealand CTRI) to 31.57% (in Deutsches Register Klinischer Studien - German Clinical Trials Register). There may be multiple reasons behind the lower percentage of observational studies in comparison to interventional studies in the registries. The first reason may be the prevalent guidelines stating that purely observational studies do not require registration. Furthermore, the majority of the biomedical journals, although made the registration of interventional studies mandatory, rarely encourage authors to preregister observational studies.[8] The registration in CTRI takes time for registration and approval of the user, filling up the form meticulously, uploading an IEC approval copy, and awaiting the confirmation. These may be inhibiting factors. In addition, the details of the study are available in an open repository. Many authors may not like to make their study details in the public domain when it is not mandatory. In contrast, many authors may be interested to register their observational trial or purely observational study in permanent repositories. Hence, in this article, we described the brief process of registration in CTRI and OSF.

Why register observational studies?

“Registered reports (RR)” is a kind of research publication where the research protocol is sent to the specific journals that publish RR. The protocol is thoroughly peer-reviewed and with input from the reviewers, the amended protocol is accepted by the journal. After the conduct of the study, the report, either positive or negative, is published.[9] In this model, the editors are no more concerned about impressive results and the authors are no more pressured to impress the editor and reviewers with a positive result. Surprisingly, it was found that replicative RR does not corroborate with original studies for 66% of the cases.[10] However, very few journals publish RR. We have discussed the RR to show how a preregistration at the journal level can reduce publication bias.

If the authors start preregistration of observational studies in public repositories, it may help the editors or the reviewers to get a credible research output for the journals. With the vigor in the protocol and robust data analysis method, the question mark for negative results is answered right away. Hence, we presume that the registration of observational studies would bring transparency in science reporting. It is suggested that when you are in doubt if the study needs registration or not, always choose to register.[5] However, we suggest that if you are going to conduct a study, register before you start collecting the data.

Permission from the Ethics Committee

For registering the study on the clinical trial registry portal - CTRI, the research protocol has to be approved from the IEC. There is controversy about the “Ethics Committee approved study” and “ethically conducted study” and Committee on Publication Ethics while discussing a case in 2003, warned the journal editors that in developing countries, ethics committee approval may be merely an administrative process.[11],[12],[13] The controversy on this may continue with positive and negative input. However, a researcher needs approval for any study on human participants or animals. What if the study is not on a human or animal?

Suppose a researcher would like to audit data available in a public domain or want to conduct a bibliographic analysis, then she/he may find difficulty in registration on the websites that are concerned about the clinical trials. In those cases, the researchers can register their studies in open registries like OSF.

Limitation of open science framework

To date, WHO or ICMJE does not accept or endorse the OSF as a repository for biomedical research. The OSF can be used by any user for the creation of a project or a public registration. The project may be kept private for collaborators, but the registration is public with a DOI. The private and public versions can be deleted by the users. In comparison to meticulous checks by expert scrutinizers in CTRI, the OSF does not provide that much vigor. These may be the reasons why it is still not accepted by the organizations such as WHO or ICMJE. Dissemination of science is evolving with a preprint server that was beyond imagination a few years back.[14] We should emphasize on transparent reporting of our studies and for the transparency preregistration is one step that can prevent publication bias. Hence, although open repositories such as OSF are not accepted by WHO or ICMJE, authors may think registering their studies for proof of credible reporting.


  Conclusion Top


Observational studies may be registered in WHO-approved and ICMJE-endorsed clinical trial registry to bring transparency in scientific reporting. A publicly available permanent record of the study protocol would help the scientific community to gain knowledge about the ongoing research. Observational studies exempted from ethical clearance may also be preregistered in an open and free repository for credible and transparent reporting. The example we described in this article would help the authors disseminating and recording their study protocol in an open repository before the starting of research.

Acknowledgment

We would like to thank Sarika Mondal and Ahana Aarshi for their support during the preparation of the manuscript.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Williams RJ, Tse T, Harlan WR, Zarin DA. Registration of observational studies: Is it time? CMAJ 2010;182:1638-42.  Back to cited text no. 3
    
4.
Should protocols for observational research be registered? Lancet 2010;375:P348. Available from: https://doi.org/10.1016/S0140-6736(10) 60148-1. [Last accessed on 2021 Jul 26].  Back to cited text no. 4
    
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Foster ED, Deardorff A. Open Science Framework (OSF). J Med Libr Assoc 2017;105:203-6.  Back to cited text no. 6
    
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Bhaskar SB. Clinical trial registration: A practical perspective. Indian J Anaesth 2018;62:10-5.  Back to cited text no. 8
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Registered Reports offer recognition for rigour. Nat Commun 2020;11:3443.  Back to cited text no. 9
    
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Chambers C. What's next for registered reports? Nature 2019;573:187-9.  Back to cited text no. 10
    
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Bmj IC. India: Doctors call for investigation into allegations of ethical abuse in COVID-19 vaccine trial. BMJ 2021;372:n131.  Back to cited text no. 11
    
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“Research” without Ethics Committee Approval. Committee on Publication Ethics. Available from: https://publicationethics.org/case/%E2%80%9Cresearch%E2%80%9D-without-ethics-committee-approval. [Last accessed on 2021 Jul 26].  Back to cited text no. 12
    
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Kaiser J. Medical Preprint Server Debuts. Science. Available from: https://www.sciencemag.org/news/2019/06/medical-preprint-server-debuts. [Last accessed on 2021 Aug 03].  Back to cited text no. 13
    
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