
==== Front
Interv Pain Med
Interv Pain Med
Interventional Pain Medicine
2772-5944
Elsevier

S2772-5944(22)00125-X
10.1016/j.inpm.2022.100129
100129
Article
Research registration guidelines
Chow Robert Robert.chow@yale.edu
∗
Rajput Kanishka
Yale New Haven Hospital, Department of Anesthesiology, New Haven, CT, USA
∗ Corresponding author. Department of Anesthesiology, Yale New Haven Hospital, 333 Cedars Street, TMP 3, New Haven, CT, 06519, USA. Robert.chow@yale.edu
15 8 2022
2022
15 8 2022
1 Suppl 2 10012928 6 2022
8 7 2022
© 2022 The Authors
2022
https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Keywords

Educational supplement
Registering research
Research guidelines
Registering guidelines
Clinical trials
Randomized controlled trials
Systematic reviews
CONSORT
PRISMA
==== Body
pmcResearch is the crux of what becomes the clinical application of science. As the pool of research grows, there is greater potential for overlapping efforts. Without a central location for these various studies, it is difficult to ensure that redundancies are minimized. In addition, there is the possibility of selective reporting of research when the outcome is undesired or inconclusive, particularly in the realm of clinical trials [1].

To address this problem, research registries were developed. Registering one's research places it in a database that can then be searched and reviewed, allowing for access to the available body of evidence. Given the growing trend of research registration, there are now numerous registries available for many different types of studies.

The purpose of this educational supplement is to serve as a guide for registering your research. In particular, registries for two main study types, randomized trials and systematic reviews, will be covered.

1 Randomized trials – CONSORT

Although the majority clinical research is now being registered, it is sometimes done in a retrospective fashion prior to submission [2]. Ideally, however it should be done in a prospective manner to facilitate proper reporting and to reduce bias [3].

Fortunately, with the CONSORT Statement the guidelines for registering one's randomized trial is very straightforward. CONSORT stands for Consolidated Standards of Reporting Trials and the CONSORT group developed a series of recommendations for reporting randomized trials.

The following is a list of the 25 elements that comprise the CONSORT Statement [4]:1. Title and Abstracta. Title – identification as a randomized trial

b. Abstract – Structured summary of trial design, methods, results and conclusions

2. Introductiona. Background – Scientific background and explanation of rationale

b. Objectives – Specific objectives or hypothesis

1.1 Methods

3. Trial designa. Description of trial design including allocation ratio

b. Important changes

4. Participants and Study settinga. Eligibility criteria for participants

b. Settings and locations where the data were collected

5. Interventions – The interventions for each group with sufficient details to allow replication, including how and when they were actually administered

6. Outcomesa. Completely defined pre-specified primary and secondary outcome measures including how and when they were assessed

b. Any changes to trial outcomes after the trial commenced, with reasons

7. Sample size and Interim analyses and stopping guidelinesa. How sample size was determined

b. When applicable, explanation of any interim analyses and stopping guidelines

8. Randomizationa. Sequence generation – Method used to generate the random allocation sequence

b. Type – details of any restriction

9. Randomization allocation concealment mechanism – Mechanism used to implement the random allocation sequence, describing any steps taken to conceal the sequence

10. Randomization implementation – Who generated the allocation sequence, who enrolled participants and who assigned the participants to interventions

11. Blinding and Similarity of interventionsa. If done, who was blinded after assignment to interventions and how

b. If relevant, description of the similarity of interventions

12. Statistics and Analysesa. Statistical methods used to compare groups for primary and secondary outcomes

b. Methods for additional analyses, such as subgroup analyses and adjusted analyses

1.2 Results

13. Participant flow and Losses and exclusionsa. For each group, the number of participants who were randomly assigned, received intended treatment, and were analyzed for the primary outcome

b. For each group, losses and exclusions after randomization, together with reasons

14. Recruitment and Reason for stopped triala. Dates defining the periods of recruitment and follow-up

b. Why the trial was ended or was stopped

15. Baseline data – A table showing baseline demographic and clinic characteristics for each group

16. Numbers analyzed – For each group, number of participants (denominator) included in each analysis and whether the analysis was by original assigned groups

17. Outcomesa. Outcome and estimation – For each primary and secondary outcome, results in each group and the estimated effect size and its precision

b. Binary outcomes – For binary outcomes, presentation of both absolute and relative effect sizes is recommended

18. Ancillary analyses – Results of any other analyses performed, including subgroup analyses and adjusted analyses, distinguishing pre-specified from exploratory

19. Harms – All important harms or unintended effects in each group

1.3 Discussion

20. Limitations – Trial limitations, addressing sources of potential bias, imprecision, and, if relevant, multiplicity of analyses

21. Generalizability – Generalizability of the trial findings

22. Interpretation – Interpretation consistent with results, balancing benefits and harms, and considering relevant evidence

1.4 Other information

23. Registration – Registration number and name of trial registry

24. Protocol – Where the full trial protocol can be accessed, if available

25. Funding – Sources of funding and other support, role of funders

After the guidelines are appropriately met, registry of the clinical trial can begin. The clinical trials registry (https://www.clinicaltrials.gov) utilizes the Protocol Registration and Results System (PRS) to register a clinical study. One must first apply for a PRS account (https://www.clinicaltrials.gov/ct2/manage-recs/how-apply) prior to beginning the registration process. The definitions for the registration data elements are also readily available (https://prsinfo.clinicaltrials.gov/definitions.html).

Currently, registration submission is via 13 different modules [5]:1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions

7. Study Design

8. Arms/Groups and Interventions

9. Outcome Measures

10. Eligibility

11. Contacts/Locations

12. IPD Sharing Statement

13. References

CONSORT Group Flow Diagram (4): Image 1

2 Systematic reviews – PRISMA

The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement was developed to facilitate transparent and complete reporting of systematic reviews and has been updated (to PRISMA 2020) to reflect recent advances in systematic review methodology and terminology. PRISMA primarily focuses on the reporting of reviews evaluating the effects of interventions, but can also be used as a basis for reporting systematic reviews with objectives other than evaluating interventions (e.g. evaluating etiology, prevalence, diagnosis or prognosis). Helpful for both authors and peer reviewers, PRISMA helps improve the reporting of systematic reviews and meta-analyses, and for critical appraisal of published systematic reviews, although it is not a quality assessment instrument to gauge the quality of a systematic review. The PRISMA 2020 statement includes a checklist of 27 items to guide reporting of systematic reviews [6].

The PRISMA 2020 statement provides updated reporting guidance for systematic reviews that reflects advances in methods to identify, select, appraise, and synthesize studies.

The PRISMA 2020 statement consists of a 27-item checklist, an expanded checklist that details reporting recommendations for each item, the PRISMA 2020 abstract checklist, and revised flow diagrams for original and updated reviews.

The following table is the most updated 2020 checklist.Section and Topic	Item #	Checklist item	Location where item is reported	
TITLE		
Title	1	Identify the report as a systematic review.		
ABSTRACT		
Abstract	2	See the PRISMA 2020 for Abstracts checklist.		
INTRODUCTION		
Rationale	3	Describe the rationale for the review in the context of existing knowledge.		
Objectives	4	Provide an explicit statement of the objective(s) or question(s) the review addresses.		
METHODS		
Eligibility criteria	5	Specify the inclusion and exclusion criteria for the review and how studies were grouped for the syntheses.		
Information sources	6	Specify all databases, registers, websites, organisations, reference lists and other sources searched or consulted to identify studies. Specify the date when each source was last searched or consulted.		
Search strategy	7	Present the full search strategies for all databases, registers and websites, including any filters and limits used.		
Selection process	8	Specify the methods used to decide whether a study met the inclusion criteria of the review, including how many reviewers screened each record and each report retrieved, whether they worked independently, and if applicable, details of automation tools used in the process.		
Data collection process	9	Specify the methods used to collect data from reports, including how many reviewers collected data from each report, whether they worked independently, any processes for obtaining or confirming data from study investigators, and if applicable, details of automation tools used in the process.		
Data items	10a	List and define all outcomes for which data were sought. Specify whether all results that were compatible with each outcome domain in each study were sought (e.g. for all measures, time points, analyses), and if not, the methods used to decide which results to collect.		
10b	List and define all other variables for which data were sought (e.g. participant and intervention characteristics, funding sources). Describe any assumptions made about any missing or unclear information.		
Study risk of bias assessment	11	Specify the methods used to assess risk of bias in the included studies, including details of the tool(s) used, how many reviewers assessed each study and whether they worked independently, and if applicable, details of automation tools used in the process.		
Effect measures	12	Specify for each outcome the effect measure(s) (e.g. risk ratio, mean difference) used in the synthesis or presentation of results.		
Synthesis methods	13a	Describe the processes used to decide which studies were eligible for each synthesis (e.g. tabulating the study intervention characteristics and comparing against the planned groups for each synthesis (item #5)).		
13b	Describe any methods required to prepare the data for presentation or synthesis, such as handling of missing summary statistics, or data conversions.		
13c	Describe any methods used to tabulate or visually display results of individual studies and syntheses.		
13d	Describe any methods used to synthesize results and provide a rationale for the choice(s). If meta-analysis was performed, describe the model(s), method(s) to identify the presence and extent of statistical heterogeneity, and software package(s) used.		
13e	Describe any methods used to explore possible causes of heterogeneity among study results (e.g. subgroup analysis, meta-regression).		
13f	Describe any sensitivity analyses conducted to assess robustness of the synthesized results.		
Reporting bias assessment	14	Describe any methods used to assess risk of bias due to missing results in a synthesis (arising from reporting biases).		
Certainty assessment	15	Describe any methods used to assess certainty (or confidence) in the body of evidence for an outcome.		
RESULTS		
Study selection	16a	Describe the results of the search and selection process, from the number of records identified in the search to the number of studies included in the review, ideally using a flow diagram.		
16b	Cite studies that might appear to meet the inclusion criteria, but which were excluded, and explain why they were excluded.		
Study characteristics	17	Cite each included study and present its characteristics.		
Risk of bias in studies	18	Present assessments of risk of bias for each included study.		
Results of individual studies	19	For all outcomes, present, for each study: (a) summary statistics for each group (where appropriate) and (b) an effect estimate and its precision (e.g. confidence/credible interval), ideally using structured tables or plots.		
Results of syntheses	20a	For each synthesis, briefly summarise the characteristics and risk of bias among contributing studies.		
20b	Present results of all statistical syntheses conducted. If meta-analysis was done, present for each the summary estimate and its precision (e.g. confidence/credible interval) and measures of statistical heterogeneity. If comparing groups, describe the direction of the effect.		
20c	Present results of all investigations of possible causes of heterogeneity among study results.		
20d	Present results of all sensitivity analyses conducted to assess the robustness of the synthesized results.		
Reporting biases	21	Present assessments of risk of bias due to missing results (arising from reporting biases) for each synthesis assessed.		
Certainty of evidence	22	Present assessments of certainty (or confidence) in the body of evidence for each outcome assessed.		
DISCUSSION		
Discussion	23a	Provide a general interpretation of the results in the context of other evidence.		
23b	Discuss any limitations of the evidence included in the review.		
23c	Discuss any limitations of the review processes used.		
23d	Discuss implications of the results for practice, policy, and future research.		
OTHER INFORMATION		
Registration and protocol	24a	Provide registration information for the review, including register name and registration number, or state that the review was not registered.		
24b	Indicate where the review protocol can be accessed, or state that a protocol was not prepared.		
24c	Describe and explain any amendments to information provided at registration or in the protocol.		
Support	25	Describe sources of financial or non-financial support for the review, and the role of the funders or sponsors in the review.		
Competing interests	26	Declare any competing interests of review authors.		
Availability of data, code and other materials	27	Report which of the following are publicly available and where they can be found: template data collection forms; data extracted from included studies; data used for all analyses; analytic code; any other materials used in the review.		

From: Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021; 372:n71. https://doi.org/10.1136/bmj.n71.

For more information, visit: http://www.prisma-statement.org/

PRISMA Flow Diagram:

PRISMA flow diagrams are one of the most employed tools to explain research methodology while performing a systematic review or meta-analysis.

The flow diagram depicts the flow of information through the different phases of a systematic review. It maps out the number of records identified, included and excluded, and the reasons for exclusions. Different templates are available depending on the type of review (new or updated) and sources used to identify studies [7].

A template is included below:Image 2

∗Consider, if feasible to do so, reporting the number of records identified from each database or register searched (rather than the total number across all databases/registers).

∗∗If automation tools were used, indicate how many records were excluded by a human and how many were excluded by automation tools.

From: Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021; 372:n71. https://doi.org/10.1136/bmj.n71.

For more information, visit: http://www.prisma-statement.org/

Additional Resources.

ICMJE accepted registries [8]:ICMJE Accepted Registries	
Registry Name	Resource Location	
Australia New Zealand Clinical Trials Registry	https://www.anzctr.org.au/	
The National Institutes of Health	https://www.clinicaltrials.gov/	
ISRCTN Registry	https://www.isrctn.com/	
UMIN Clinical Trials Registry	https://www.umin.ac.jp/ctr/index/htm/	
EudraCT	https://eudract.ema.europa.eu/	

Additional guidelines by study type [9]:Guidlines by Study Type	
Study Type	Guidelines	Resource Location	
Observational Study	STROBE	https://www.strobe-statement.org/	
Case Reports	CARE	https://www.care-statement.org/	
Clinical Practice Guidelines	AGREE	https://www.agreetrust.org/practice-guidelines/	
Qualitative Research	SRQR	https://pubmed.ncbi.nlm.nih.gov/24979285/	
Quality Improvement Studies	SQUIRE	http://www.squire-statement.org/	
Economic Evaluations	CHEERS	https://www.ispor.org/heor-resources/good-practices/cheers	

NIH Clinical Research Trials List of Registries:

https://www.nih.gov/health-information/nih-clinical-research-trials-you/list-registries.

Systematic Review Protocols and Protocol Registries

https://www.nihlibrary.nih.gov/services/systematic-review-service/systematic-review-protocols-and-protocol-registries.

Declaration of competing interests

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
==== Refs
References

1 De Angelis C. Clinical trial registration: a statement from the international committee of medical journal editors Lancet 364 2004 Sep 911 912 15364170
2 El-Boghdadly K. Adherence to guidance on registration of randomized controlled trials published in Anaesthesia Anaesthesia 73 2018 556 563 29292498
3 Harriman S. When are clinical trials registered? An analysis of prospective versus retrospective registration Trials 17 2016 187 27079379
4 CONSORT Group. Consolidated Standards of Reporting Trials (CONSORT) Statement. http://www.consort-statement.org/(accessed 06/23/2022).
5 Clinicaltrials.gov. PRS Guided Tutorials. https://prsinfo.clinicaltrials.gov/tutorial/content/index.html#/(accessed 06/23/2022).
6 Page M.J. McKenzie J.E. Bossuyt P.M. Boutron I. Hoffmann T.C. Mulrow C.D. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews BMJ 372 2021 n71 33782057
7 PRISMA PRISMA TRANSPARENT REPORTING of SYSTEMATIC REVIEWSand META-ANALYSES 2020 https://prisma-statementorg/
8 International Committee of Medical Journal Editors. Clinical Trials Registration. https://www.icmje.org/about-icmje/faqs/clinical-trials-registration/(accessed 06/23/2022).
9 Equator Network. Enhancing the QUAlity and transparency of health research. https://www.equator-network.org/reporting-guidelines/(accessed 06/23/2022).
