Registering clinical trials
All clinical trials started after January 1, 2006 must be registered. The ICMJE defines a clinical trial as any research project that prospectively assigns human subjects to intervention or concurrent comparison or control groups to study the cause-and-effect relationship between a medical intervention and a health outcome. Medical interventions include drugs, surgical procedures, devices, behavioural treatments, process-of-care changes and the like.
In addition to accepting registration in any of the five existing registries (for example, ClinicalTrials.gov), the ICMJE will now also accept registration of clinical trials in any of the primary registers that participate in the World Health Organization's (WHO) International Clinical Trial Registry Platform (ICTRP). It should be noted that registration in a partner register only will not suffice.
The ICMJE is expanding the definition of the types of trials that must be registered and will begin to implement the WHO definition of clinical trials for all trials that begin enrolment on or after July 1, 2008. The WHO's definition of clinical trials is: "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".
The ICMJE does not consider results posted in the same clinical trials registry in which the primary registration resides to be previous publication if the results are presented in the form of a brief (<500 words) structured abstract or table. When submitting to the ERJ, authors should specify where the clinical trial is registered and disclose all posting in registries of results of the same or closely related work.
For further details on current ICMJE policy, see ICMJE or read N Engl J Med 2007; 356: 2734-2736.
Guidelines on reporting research findings
Randomised controlled trials must conform to the CONSORT statement, which provides a set of recommendations comprising a list of items to report and a patient flow diagram.
For other study designs, authors are strongly recommended to consult the following reporting guidelines: studies of diagnostic accuracy (STARD); systematic reviews and meta-analyses (QUOROM); observational studies in epidemiology (STROBE); and meta-analyses of observational studies in epidemiology (MOOSE).
Manuscript preparation
Presentation of manuscripts should conform to the updated Uniform Requirements for Manuscripts Submitted to Biomedical Journals (see
icmje).
All manuscripts must be submitted electronically using the online submission at:
manuscriptcentral
from now on referred to as ERJ Manuscript Central. Detailed instructions of how to submit are available on the website itself and the process is self explanatory. However, if you do experience problems, please contact the Submission Helpline direct on +44 114 2672864 or contact Gill Archer, the manuscript central coordinator.
Before entering the ERJ Manuscript Central online submission area, please read and carefully follow the instructions below.
For further guidance on how to write papers, please see: Sterk PJ, Rabe KF. The joy of writing a paper. Breathe 2008; 4: 224-232.
General
- The manuscript file you submit must be saved as .rtf (rich text format) or .doc (MS Word document).
- Original articles should not exceed 3,000 words, not including abstract, references, tables and legends. However, if manuscripts do exceed this limit, please state the final word count and explicit reasons for exceeding the limit in your covering letter.
- Figures and/or tables should be limited to eight altogether.
- Abbreviations or unusual terms should be described at the first time of use.
- Symbols as defined by the ad hoc working group of the Commission of the European Communities (see Eur Respir J 1993; 6: Suppl. 16) are recommended.
- Système International (SI) units are recommended.
- Equations should be created as normal text.
Title page
- Please provide a concise and informative title, limited to 90 characters, including spaces between words.
- Include a list of all contributing authors and all of their affiliations, with a clear indication of who is associated with each institution.
- Supply the full correspondence details for the corresponding author, including e-mail address and fax number.
- Provide a short title for the manuscript, limited to 45 characters, including spaces between words.
Abstract
- Please provide an abstract of 200 words or fewer, which is easily understood without reference to the text (see Ann Intern Med 1987; 106: 598–604).
- The abstract must have four separate paragraphs, which correspond to the question of the study, materials/patients and methods, results, and the answer to the question. One or two sentences of background information can be included before the question if necessary. The question and answer should be the same as those in the text.
- Include only a few important values.
- Avoid using abbreviations and reporting statistics.
Keywords
- Please provide a list of 6 keywords or fewer.
- The keywords should be listed alphabetically.
- The keywords should be listed in full without abbreviations.
Introduction
- State the question you asked (or hypothesis to be tested) and your considerations leading to the formulation of the question.
- Give only pertinent references.
Material and methods
Study subjects or animals
- Clearly describe how the subjects or experimental animals were identified, including the control subjects when used. For animals, see Laboratory Animals 1985; 19: 106–108.
- Clearly state the eligibility criteria for cases and controls in observational studies, or for subjects in clinical trials.
- All work involving studies on human subjects is expected to have received approval from local Ethical Committees and the regulatory authority (when appropriate, for example, drug trials).
- Animal experimentation must be performed according to the Helsinki convention for the use and care of animals.
- The Editors reserve the right to refuse work which does not conform to acceptable ethical criteria.
Study design
- Clearly state the main study objective(s).
- Provide an overview of the main tests or experiments.
- Consider sample size and whether you have enough subjects to reliably address the research question.
- Papers on clinical trials should include details of the sample size calculation (i.e. the expected effect size, power, level of statistical significance and one- or two-sided test). The sample size should be reproduced independently.
Methods
- Describe the methods and apparatus in sufficient detail to allow other workers to evaluate or reproduce the tests/experiments.
- For methods that have been published before, provide only a reference or a reference and a brief description.
- Identify drugs and chemicals, including generic name, dosage and route of administration.
- Please provide manufacturer and manufacturer's address for equipment, drugs and chemicals, as necessary, but not in a separate section.
- For systematic reviews, make sure that the keywords used to search electronic medical databases cover different terminology (for example, tumour or cancer) and spelling (for example, randomised or randomized).
Analysis
- Clearly state and define the main outcome measure(s).
- Briefly state the statistical methods used during the analysis if they are standard. New methods should be described with justification.
- In the case of single- or multicentre trials with blinded intervention, the code must have been broken at the end of the study in the presence of the responsible investigator of each centre. The code and the data will then be available to each participating centre. The first author should make provisions so that if needed, the data are available to the ERJ for independent statistical analysis.
- See the Statistical Notes below for further information on analysis, presentation and interpretation
Results
- Keep the Results section brief.
- Describe the baseline characteristics or condition of patients or animals.
- Focus on the important results, i.e. those that help address the research question.
- Present most data in figures or tables, not in the text. In the text, emphasise or summarise the most important observations.
Discussion
- At the beginning of the Discussion, summarise the main results, and show how they have addressed the research question.
- Make sure that the conclusions are consistent with the results and are pertinent to the research question.
- Describe the limitations of the study and/or analysis, and discuss the possible implications on the conclusions.
- Emphasise the new and important aspects of the study.
- Try to explain contradictory or unexpected results, or discrepancies with previous findings.
Acknowledgements
- All acknowledgements should be grouped into one paragraph placed after the Discussion.
- Only acknowledge persons who have made substantial contributions to the study.
References
- Number references consecutively in the order in which they first appear in the text, using full size Arabic numerals in square brackets.
- All authors must be included in the reference list.
- For original articles, the number of references should be limited to 30.
- References should conform to the style used in Index Medicus (Vancouver Style) as shown in the following examples:
- 1. Bannerjee D, Khair OA, Honeybourne D. Impact of sputum bacteria on airway inflammation and health status in clinical stable COPD. Eur Respir J 2004; 23: 685–692.
- 2. Bourbon J, Henrion-Caude A, Gaultier C. Molecular basis of lung development. In: Gibson GJ, Geddes DM, Costable U, Sterk PJ, Corrin B, eds. Respiratory Medicine. 3rd Edn. Elsevier Science, Edinburgh/Philadelphia, 2002; pp. 64–81.
- Websites should be listed in the reference list, not in the text, and only used when an original citation is unavailable; citations should be listed as follows:
- WHO. Severe Acute Respiratory Syndrome (SARS). www.who.int/csr/sars/en/index.html. Date last updated: June 1 2004. Date last accessed: June 1 2004.
- Work which has not yet been accepted for publication and personal communications should not appear in the reference list.
- One copy of papers cited as “in press” should be uploaded onto manuscript central as supplementary material.
Tables
- Tables should be created and inserted into the text document using the “Table”, “Insert Table” function in your word processing package; DO NOT supply tables in a separate file.
- Tables should be numbered consecutively with Arabic numerals.
- Limit decimals to a sensible number.
- Large tables should be avoided due to space restrictions, and if used may be split.
- Please provide a clear footnote for all tables, making sure ALL abbreviations and symbols used are defined.
- Any references in tables should run on in numerical order from the text where the table is cited.
Figures
- Figures constitute a key element of manuscripts submitted to the ERJ. However, figures should be limited to those required to show the essential features described in the manuscript. Redundant or excessive figures will not be published due to space restrictions.
- All submitted figures must be named and numbered. If labelling is necessary, see a recent issue of the ERJ for the degree of labelling required.
- There is a charge for colour figures; however, a discounted rate is available to Members. Please contact the Publications Office for further details.
- Please attempt to keep each figure under 1 megabyte (MB). If it is over 1 MB, the upload time will be considerably increased; likewise, the download time could be significantly increased.
- Whether for images, drawings, or graphs, we recommend that no more than four components be used for a given figure (e.g. a, b, c, d).
- Images embedded in the .doc or .rtf file WILL NOT be accepted.
- The ERJ strongly discourages the use of previously published figures unless absolutely essential. Use of such figures is problematic because permission has to be obtained by yourself from the copyright owner, which is usually the publisher and NOT the original author, and this may involve a fee payable to the original publisher. Please note that some publishers will not provide permission for publication, which precludes these figures from being displayed in both the printed and the on-line version of the ERJ.
Photographic images
- All photographic images should be provided with a minimum of 300 dots per inch (dpi).
- Figures should preferably be supplied in .jpeg, .tif or .eps format.
- The image mode for colour photographic images should be cyan-magenta-yellow-black (CMYK). For black-and-white photographic images, it should be grey scale.
- An image-editing program such as Adobe Photoshop© is recommended for saving images.
- Due to space restrictions, it is essential that each submitted figure show only the areas of interest with enough surrounding area for orientation purposes.
- Radiographic images should be of high quality and combined into one array, such as posteroanterior and lateral views. They should also be sized the same to facilitate reproduction.
- Image size should be submitted as close as possible to print size; one column width is 88 mm, two-column width is 182 mm.
- When several images of a given type are being shown, please reproduce each specific type at the same magnification.
- Photomicrographs must have internal scale markers (linear scale), since the size and magnification may be altered by the publisher.
- Images should correspond in appearance to the tonal relations of the original radiograph (i.e. showing the bones white on a dark background, with the patient’s right to the observer’s left. CT scans and MR images should employ the internationally-accepted “view from below”.
- Please label your images such that all important details are clearly visible.
Guidelines for handling image data
- If an image has been enhanced electronically, please explain the alterations that have been made and send in the original image along with the enhanced one. Moreover, keep an electronic set of original images, since our Reviewers might ask you to modify their content and the display modus.
- The Council of Science Editors (CSE) has established four basic guidelines for handling image data, which authors submitting to the ERJ are urged to comply with. 1) No specific feature within an image may be enhanced, obscured, removed or introduced. 2) Adjustments of brightness, contrast or colour balance are acceptable if they are applied to the whole image and as long as they do not obscure, eliminate or misrepresent any information present in the original. 3) The grouping of images from different parts of the same gel, or from different gels, fields or exposures must be made explicit by the arrangement of the figure (e.g. dividing lines) and in the text of the figure legend. 4) If the original data cannot be produced by an author when asked to provide it, the acceptance of the manuscript may be revoked.
Legends
- Please provide a clear legend for each figure.
- Legends should be brief and nonrepetitive of information given in the text.
- They should include the imaging technique used, the body part imaged and any noteworthy details.
- ALL abbreviations should be expanded.
- Use of internal scales should always be mentioned in the legend.
Online depository
The ERJ has an online depository, which can be used to provide more detailed methodology (which does not need to be included in the Materials and Methods section of the paper), supplementary data or figures, and accompanying videos. This is an optional function and can be used at the discretion of the author and/or Editor. Documents should be uploaded as "Supplementary material".
Authors should note that their supplementary material will not be edited by the Editorial Office, and will be put online as it has been supplied.
Short Reports and Case Studies
The general presentation should follow the same pattern as full papers but the total length should not exceed 1,500 words, not including figures, tables and the reference list.
“Case Studies” should provide new knowledge on aetiology, mechanism, diagnosis or treatment of a disease.
Cases for Diagnosis
A Case for Diagnosis should be prepared as shown in the ERJ, e.g. 2001; 18: 432–435.
Submitted Case Studies or Case for Diagnosis may be accepted for either the Learning Resource Centre on the ERS website, or, in exceptional circumstances, when the Case Study or Case for Diagnosis is sufficiently novel, it may be published in the ERJ.
Correspondence
Letters to the Editor are welcomed but they should be limited to 700 words and no more than 10 references.
Rapid publications
Concise communications of significant scientific importance that deserve rapid publication in order to accelerate research in their field will be considered for rapid publication.
Only completed original studies requiring limited revision will be accepted. In the covering letter, the request for rapid publication should be stated, together with a justification.
Length should not exceed 3,000 words, including figures and tables.
Authors will be notified about the editorial decision within 4 weeks of receipt and accepted manuscripts will be published within 3 months.
If the manuscript is rejected for rapid publication, the authors may not receive detailed reviewers’ comments, but will be allowed to submit as a regular manuscript.
ERJ In press
All original articles that have been accepted are published online before they have been selected to appear in a printed issue of the ERJ. None of the additional editorial preparation, which includes copy-editing, typesetting and proofreading, has been performed at this stage. ERJ In press provides authors and readers with immediate, subscription-based access to the newest research.
Proofs and reprints
A proof will be sent by e-mail (pdf file) or fax to the corresponding author.
It should be corrected and returned to the ERJ Production Office within 48 hours by fax, email or express mail (for address and number, see below). Late return will delay publication. Modification to proofs should be limited to typographical errors only.
Statistical notes
Seek help or advice from a statistician on the appropriate methods of analyses and whether the results have been interpreted correctly.
Study design
- By clearly describing how the subjects were selected you could see whether there are any factors that could distort the results.
- Where appropriate (particularly observational studies), give reasons why many eligible patients were not included in the study.
- Meta-analyses of only a few small randomised trials, for example, 3 or 4, could be affected by publication bias, and the statistical power to detect heterogeneity is likely to be low. It might therefore be worthwhile checking whether there are large observational studies that could provide additional information.
Displaying data
- Many studies are based on relatively few subjects, for example, less than 50. A scatter plot is a good way of showing the data.
- When examining associations between two continuous variables, present scatter plots, possibly showing a regression line or curve.
- Bar charts are useful when displaying comparisons of percentages (or proportions) between several groups.
Analysis
- Check whether the variables are normally distributed (e.g. using a probability plot). If they are, the statistical methods are usually much easier to perform.
- When analysing data, be clear about what the outcome measure involves:
- Counting people or objects (binary or categorical data).
- Taking measurements on people or objects (continuous data).
- Time-to-event data (for example, survival data).
- When making comparisons between groups, provide estimates of effect sizes and the corresponding confidence interval and p-value (table 1).
Table 1. Effect sizes and common statistical tests that produce p-values
|
Counting people or objects |
Taking measurements on people or objects |
Time-to-event data |
Effect size |
- Relative risk
- Risk difference
- Percentage change in risk
|
- Difference between 2 means
- Difference between 2 medians
|
- Hazard ratio
- Risk difference at a specific time point
|
Two separate groups, 1 measurement (unpaired data) |
Chi-square test |
Unpaired or two-sample t-test if the difference between the means is normally distributed# |
Log rank test |
|
Mann-Whitney test if distribution of the difference is skewed¶ |
|
One group, 2 repeated measurements (paired data) |
McNemar’s test |
Paired t-test if the difference is normally distributed |
Not applicable |
|
Wilcoxon matched pairs test if the distribution of the difference is skewed |
|
Allow for other factors |
Multivariate logistic regression |
Multivariate linear regression+ |
Cox regression |
#: with more than two arms in the trial, the test is ANOVA; ¶: with more than two arms in the trial the test is Kruskal-Wallis ANOVA; +: outcome measure is approximately normally distributed.
All main effect sizes should be reported whether statistically significant or not, including confidence intervals and p-values.
Know which statistical method to use and when.
When many variables (or associations) are examined in the same data set (multiple testing), researchers are more likely to find a spurious effect or association. The authors should consider adjusting p-values for multiple comparisons or provide 99% confidence intervals.
When reporting statistical significance, do not present "NS" (i.e. not statistically significant), "p>0.05" or "p≤0.05". Show p-values as <0.001 or to 2 or 3 decimal places otherwise.
Be clear about repeated measures data. A study of 10 repeated measurements of a variable on 10 subjects is not the same as 1 measurement on 100 subjects; there are still only 10 subjects. Repeated measurements are likely to be correlated with each other, and this needs to be taken into account in the analysis.
Subgroup analyses tend not to produce reliable results if there are (a) too few patients or (b) too few events.
For screening or diagnostic studies use "detection rate" (sensitivity) and "false-positive rate" (1 minus specificity). The word sensitivity can sometimes be confused with the same term in laboratory studies. Using specificity to compare two tests can mask an important difference. For example, specificities of 96% versus 98% both look high. However, the corresponding false-positive rates are 4% versus 2% (one is twice as large as the other).
For screening or diagnostic tests, if the same data set is used both to derive the model and to test the model (i.e. estimate performance), the performance of the test is often over-estimated. Authors should acknowledge this in the Discussion, and recommend independent studies to confirm the findings.
Interpretation
- If a p-value is >0.05, it does NOT mean that there is no effect or association. Furthermore, a p-value of 0.06 can have a different conclusion than a p-value of 0.75. If a result is "not statistically significant", according to the conventional cut-off of 0.05, the possible reasons are:
- There really is no effect.
- There is a real effect, but by chance the sample of patients did not show this.
- There is a real effect, but the study was too small to detect it.
If a clinically important effect is observed but the p-value is, say, 0.06, it is likely that the study was not large enough. Such data are suggestive of an effect.
Where studies are hypothesis-generating or based on a small sample size, authors should make it clear that any conclusions should be tested in an independent study. The conclusions should not be strong.
Clinical trials and observational studies
- When designing and reporting trials, consider how to write them up.
- See the section Guidelines on reporting research findings for links to published guidelines associated with clinical studies.
- These guidelines provide an idea of how to structure your report and what to include.
Sources of information for statistical analyses, study design and data presentation
The Statistical Advisors of the ERJ recommend the following series of papers on the use of statistics, in particular those articles on repeatability, reproducibility, regression and correlation analyses and confidence intervals, and comparisons of means and proportions.
- Bland JM, Altman DG. Correlation, regression and repeated data. BMJ 1994; 308: 896.
- Bland JM, Altman DG. Regression towards the mean. BMJ 1994; 308: 1499.
- Altman DG, Bland JM. Diagnostic tests 1: sensitivity and specificity. BMJ 1994; 308: 1552.
- Altman DG, Bland JM. Diagnostic tests 2: predictive values. BMJ 1994; 309: 102.
- Altman DG, Bland JM. Diagnostic tests 3: receiver operating characteristic plots. BMJ 1994; 309: 188.
- Bland JM, Altman DG. One- and two-sided tests of significance. BMJ 1994; 309: 248.
- Bland JM, Altman DG. Some examples of regression towards the mean. BMJ 1994; 309: 780.
- Altman DG, Bland JM. Quartiles, quintliles, centiles, and other quantiles. BMJ 1994; 309: 996.
- Bland JM, Altman DG. Matching. BMJ 1994; 309: 1128.
- Altman DG, Bland JM. The normal distribution. BMJ 1995; 310: 298.
- Bland JM, Altman DG. Calculating correlation coefficients with repeated observations: Part 1, correlation within subjects. BMJ 1995; 310: 446.
- Bland JM, Altman DG. Calculating correlation coefficients with repeated observations: Part 2, correlation between subjects. BMJ 1995; 310: 633.
- Altman DG, Bland JM. Absence of evidence is not evidence of absence. BMJ 1995; 311: 485.
- Bland JM, Altman DG. Multiple significance tests: the Bonferroni method. BMJ 1995; 310: 170.
- Altman DG, Bland JM. Presentation of numerical data. BMJ 1996; 312: 572.
- Bland JM, Altman DG. Logarithms. BMJ 1996; 312: 700.
- Bland JM, Altman DG. Transforming data. BMJ 1996; 312: 770.
- Bland JM, Altman DG. Transformations, means and confidence intervals. BMJ 1996; 312: 1079.
- Bland JM, Altman DG. The use of transformations when comparing two means. BMJ 1996; 312: 1153.
- Altman DG, Bland JM. Comparing several groups using analysis of variance. BMJ 1996; 312: 1472–1473.
- Bland JM, Altman DG. Measurement error. BMJ 1996; 313: 744
- Bland JM, Altman DG. Measurement error and correlation coefficients. BMJ 1996; 313: 41–42.
- Bland JM, Altman DG. Measurement error proportional to the mean. BMJ 1996; 313: 106.
- Altman DG, Matthews JNS. Interaction 1: Heterogeneity of effects. BMJ 1996; 313: 486.
- Matthews JNS, Altman DG. Interaction 2: compare effect sizes not P values. BMJ 1996; 313: 808.
- Matthews JNS, Altman DG. Interaction 3: How to examine heterogeneity. BMJ 1996; 313: 862.
- Altman DG, Bland JM. Detecting skewness from summary information. BMJ 1996; 313: 1200.
- Bland JM, Altman DG. Cronbach's alpha. BMJ 1997; 314: 572.
- Altman DG, Bland JM. Units of analysis. BMJ 1997; 314: 1874.
- Bland JM, Kerry SM. Trials randomised in clusters. BMJ 1997; 315: 600.
- Kerry SM, Bland JM. Analysis of a trial randomised in clusters. BMJ 1998; 316: 54.
- Bland JM, Kerry SM. Weighted comparison of means. BMJ 1998; 316: 129.
- Kerry SM, Bland JM. Sample size in cluster randomisation. BMJ 1998; 316: 549.
- Kerry SM, Bland JM. The intra-cluster correlation coefficient in cluster randomisation. BMJ 1998; 316: 1455.
- Altman DG, Bland JM. Generalisation and extrapolation. BMJ 1998; 317: 409–410.
- Altman DG, Bland JM. Time to event (survival) data. BMJ 1998; 317: 468–469.
- Bland JM, Altman DG. Bayesians and frequentists. BMJ 1998; 317: 1151.
- Bland JM, Altman DG. Survival probabilities (the Kaplan-Meier method). BMJ 1998; 317: 1572.
- Altman DG, Bland JM. Treatment allocation in controlled trials: why randomise? BMJ 1999; 318: 1209.
- Altman DG, Bland JM. Variables and parameters. BMJ 1999; 318: 1667.
- Altman DG, Bland JM. How to randomise. BMJ 1999; 319: 703–704.
- Bland JM, Altman DG. The odds ratio. BMJ 2000; 320: 1468.
- Day SJ, Altman DG. Blinding in clinical trials and other studies. BMJ 2000; 321: 504.
- Altman DG, Schulz KF. Concealing treatment allocation in randomised trials. BMJ 2001; 323: 446–447.
- Vickers AJ, Altman DG. Analysing controlled trials with baseline and follow up measurements. BMJ 2001; 323: 1123–1124.
- Bland JM, Altman DG. Validating scales and indexes. BMJ 2002; 324: 606–607.
- Altman DG, Bland JM. Interaction revisited: the difference between two estimates. BMJ 2003; 326: 219.
- Bland JM, Altman DG. The logrank test. BMJ 2004; 328: 1073.
- Deeks JJ, Altman DG. Diagnostic tests 4: likelihood ratios. BMJ 2004; 329: 168–169.
- Altman DG, Bland JM. Treatment allocation by minimisation. BMJ 2005; 330: 843.
- Altman DG, Bland JM. Standard deviations and standard errors. BMJ 2005; 331: 903.
- Altman DG, Royston P. The cost of dichotomising continuous variables. BMJ 2006; 332: 1080.
- Altman DG, Bland JM. Missing data. BMJ 2007; 334: 424.
- Petrie A, Sabin C. Medical Statistics at a Glance. 2nd Edn. Blackwell Publishing, 2006.
- Kirkwood B, Sterne JAC. Essential Medical Statistics. 2nd Edn. Blackwell Science, 2003.
- Bland M. Introduction to Medical Statistics. 3rd Edn. Oxford University Press, 2000.
- Barker DJP, Rose G. Epidemiology in Medical Practice. 5th Edn. Elsevier, 1997.
- Rothman KJ. Epidemiology: an Introduction. Oxford University Press, 2002.
- Silman AJ, Macfarlane GJ. Epidemiological Studies: a Practical Guide. 2nd Edn. Cambridge University Press, 2002.
Links 1-53 provided with kind permission from the BMJ.
Copyright © 2008 by the European Respiratory Society.