This article was originally published in Japanese in Japanese Journal of Breast Cancer 2013; 28(6):

575–580. The English version of this article has been reproduced with permission from the Japanese Journal of Breast Cancer.

WRITING A CLINICAL MANUSCRIPT IN ENGLISH THAT HAS IMPACT

Amanda Hindle, BSc*†, Jeffrey Robens, PhD*, Daniel McGowan, PhD*

Edanz Group Japan, Edanz Bldg. 2-12-13 Minato, Chuo-ku, Fukuoka 810-0075, Japan

*All authors contributed equally to this article

†Corresponding author:

Amanda Hindle

Edanz Group Japan, Edanz Bldg. 2-12-13 Minato, Chuo-ku, Fukuoka 810-0075, Japan

Tel: +81 92 715 7208

Fax: +81 92 715 7204

Email: ahindle@edanzgroup.com

SUMMARY

Writing a clinical manuscript that has impact and relevance to your intended

audience is crucial for publication success. Furthermore, publishing in English will

increase the visibility of your research worldwide. However, effectively

communicating the clinical relevance of your research in English is particularly

challenging if it is not your native language. In this article, we focus on the essentials

of what makes a high-quality clinical manuscript. Understanding these essentials will

assist you in writing a well-structured, ethically sound, and highly readable

manuscript that clearly expresses the clinical relevance of your findings. Using these

approaches, you can be confident that your work adheres to the standards of

international English language journals, and improve your chances of publication

success.

Keywords: clinical relevance, manuscript structure, medical writing

This article was originally published in Japanese in Japanese Journal of Breast Cancer 2013; 28(6):

575–580. The English version of this article has been reproduced with permission from the Japanese Journal of Breast Cancer.

INTRODUCTION

As a clinician, you may have treated a patient with a unique presentation, or you may

have been involved in a clinical trial to investigate a novel intervention. Either way,

sharing your findings with the medical community is an important way to improve clinical

practice both regionally and internationally. The most effective way to reach the greatest

number of clinicians is through publishing your findings in a peer-reviewed journal.

One important choice you will need to make as an author is in what language to publish

your findings. Publishing in your native language is one option; however, the best way to

reach international clinicians in your field is to publish in English. Even if your findings

have a regional focus, they are likely to have broad relevance to clinicians worldwide, as

observations about the effects of a drug tested in Japan will be of direct interest to

clinicians in other countries treating patients of Japanese ethnicity.

Before writing, however, it is important to understand what journal editors are looking for

when evaluating manuscripts. Because the goal of the journal editor is to increase the

status of their journal in their field, they are interested in high-quality research. This is

research that is original and novel and has important clinical relevance. They are looking

for manuscripts that will be interesting for their readers and will be highly cited. They also

want manuscripts that are written in clear and concise English. This does not simply

mean good spelling and grammar, but rather manuscripts that clearly and effectively

communicate the ideas and findings of the authors. In this paper, we expand on each of

these topics to ensure you have all the essentials to prepare a clinical manuscript for

publication in an English journal.

ELEMENTS OF A GOOD CLINICAL MANUSCRIPT

Clinical relevance

Although there are journals that will accept articles simply based on well-executed

research, other journals (especially those with a higher impact factor) will place a greater

emphasis on the significance of the findings presented. But what does this “significance”

actually encompass? Broadly, it is an indication of the importance of an article’s findings,

which for the purposes of this review can be divided into three components: novelty,

relevance, and appeal.

It is essential to perform and honest and objective evaluation of your findings and to

clearly communicate the novelty, relevance and appeal of your findings in the manuscript

This article was originally published in Japanese in Japanese Journal of Breast Cancer 2013; 28(6):

575–580. The English version of this article has been reproduced with permission from the Japanese Journal of Breast Cancer.

text. Whilst one should not overuse terms like “for the first time” and “never before”, if

your findings represent a conceptual advance in the field, you should emphasize the

novelty of your findings to ensure readers are aware of this advance. However, if your

findings represent a smaller advance in the field, you should focus more on how they will

help improve current practice or inform the next steps in a research path.

With respect to the relevance of your findings, you should consider whether they have

implications for only a restricted geographical location or ethnic group, or whether there

are potential implications for broader regions and populations. The broader the

relevance of the findings, the greater the significance and impact worldwide. However,

regardless of whether you publish in an international or regional journal, you should still

publish in English to make your findings available to an international audience.

It is important to remember that journal editors want to publish research that will be

widely read and achieve a high number of citations. In an age of blogs, newsfeeds, and

social networks, research that has a high level of popular appeal will likely achieve

greater numbers of citations simply because more people will be made aware of the

publication. Therefore, it is important to identify important research questions and

emphasize the clinical applications of your research in your manuscript.

Figure 1. Novelty, relevance and appeal in a good-quality oncology manuscript. The selected article [1] was

among the journal’s “most viewed” in the month of publication. The reason for this, we believe, is that it

contained all of the components of significance discussed herein (novelty, relevance and appeal) and these

were clearly pointed out in the manuscript text.

This article was originally published in Japanese in Japanese Journal of Breast Cancer 2013; 28(6):

575–580. The English version of this article has been reproduced with permission from the Japanese Journal of Breast Cancer.

While all three of these components of significance are clearly inter-related, each should

be considered independently and emphasized in the manuscript to ensure that the

significance of the article is clearly communicated. Figure 1 illustrates how this was done

in a highly viewed article in a top-tier journal [1]. As well as containing findings that were

clearly of great significance, the article outlined in Figure 1 also contains many of the

important qualities that editors and readers look for in a medical oncology paper (Table

1). Indeed, regardless of the significance of the findings being presented and the journal

being submitted to, authors of clinical research articles should aim to include all of the

items listed in the table somewhere within their manuscript. In putting these elements

together, a really good clinical manuscript contains information that influences clinical

practice based on the most appropriate methods for the research question [2,3].

Table 1. Qualities of a good medical oncology paper

Feature Example

Accurate, objective reporting of methodology and results

Enough information in methods to replicate; clear rationale; calculation of statistical power; limited interpretation of results in the Results section

Concise illustrations and descriptions

Figures showing key outcomes such as progression-free survival, overall survival and response rates; table listing adverse events

Insightful and objective discussion Findings put in context of what is known; limited speculation, but statements are supported by evidence

Full disclosure and registered trial Registry and registration number provided

Full ethical compliance Details of institutional review board approval and informed consent provided

Multiple, complementary, well-controlled experiments

Combination of imaging, pathology and clinical work-up to tell a more convincing story

Mechanistic findings to complement clinical findings

Cellular/biochemical-level findings to support descriptions of clinical effects

Clear description of clinical implications and how the findings might influence clinical practice

What the results mean for patients and how clinical decisions might be improved on the basis of the presented findings

This article was originally published in Japanese in Japanese Journal of Breast Cancer 2013; 28(6):

575–580. The English version of this article has been reproduced with permission from the Japanese Journal of Breast Cancer.

Clear writing

Good science alone, however, is not enough to make a good manuscript. Effective

writing is also needed to clearly communicate your ideas. If your ideas are not expressed

clearly, even experts in the field may not understand what you did and why, limiting the

clinical applicability of your findings.

The key element you are trying to achieve with your writing style is good readability. This

refers to the logical presentation of ideas and organization of material in places where

readers expect to find it. It is crucial to remember that you are writing for the reader; the

purpose of a manuscript is to share your work with others, not simply create a personal

record of your results.

Without realizing it, readers expect certain information to appear in certain places within

a text. By considering these reader expectations in your writing, you can enhance the

readability of your manuscript as readers can easily find the information they are looking

for. Gopen and Swan proposed a methodological approach for constructing the ideas

within a manuscript that would provide the reader with the important clues and cues to

properly interpret an author’s meaning [4]. The key concepts they outlined included

logically connecting ideas together with the use of topic sentences and reference back to

previous ideas, emphasizing shorter sentences, and keeping subjects and verbs close

together. They also encouraged good use of what are known as the topic position

(beginning) and stress position (end) of a sentence to introduce the reader to the next

concept and emphasize the important message, respectively.

However, a well-constructed paragraph can still have poor readability if you do not also

consider the language being used. Many researchers think that complicated language

makes their writing appear more sophisticated. Unfortunately, use of unnecessarily long

words and technical jargon actually make your work harder to understand. Editors are

not impressed with complicated language; they are concerned primarily with the science

behind it. It is also important to consider that many of your readers might not be native

English speakers. Therefore, to maximize the accessibility of your findings and ideas,

simple, unambiguous language should be used.

Manuscript structure and flow

Equally important to the clear communication of your ideas and results in terms of

language, is the logical presentation of those ideas. The sections and order of a research

This article was originally published in Japanese in Japanese Journal of Breast Cancer 2013; 28(6):

575–580. The English version of this article has been reproduced with permission from the Japanese Journal of Breast Cancer.

paper allow your readers to logically move from an overview of your research (Abstract),

to why the study was conducted (Introduction), to how your results were obtained

(Methods), to the significance of your findings (Results), and finally, to the implications

your results have for the field (Discussion). Figure 2 illustrates this basic structure of a

manuscript and how these sections relate to one another.

Figure 2. Manuscript structure and flow. Logically presenting your findings and showing how they fit into the

context of current knowledge is essential to a highly readable and well-organized manuscript. This figure

illustrates how to arrange your ideas from a broad introduction (upper funnel) down to the specifics of your

objectives and methods (narrow center), and finally back to the broader clinical relevance of your findings

(bottom triangle), producing an hourglass-type shape. To the left, the corresponding sections of the

manuscript are noted. Arrows indicate the important areas where ideas should be linked back to each other

to create flow and strengthen the logical presentation of your work.

The first impression that the Abstract provides is part of what makes it the most important

section of your manuscript. Readers are also busy with their own work, so they will use

the Abstract to determine which articles to read. Thus, a well-written and

well-communicated Abstract has the potential to increase the number of people who

read your article, leading to more citations, and ultimately, your research having a

greater impact in the field.

Although Abstract structure can vary based on the journal guidelines, they generally

follow a similar format. Abstracts distill the most important parts of each section of the

manuscript into one concise summary, so you can consider it to be a mini version of your

manuscript. However, it is important to emphasize the clinical impact of your study, as

that is often what will convince a reader that your research is relevant to them.

This article was originally published in Japanese in Japanese Journal of Breast Cancer 2013; 28(6):

575–580. The English version of this article has been reproduced with permission from the Japanese Journal of Breast Cancer.

As the start of your primary manuscript, the Introduction section should concisely present

the topic being investigated and the related problem clinicians are currently facing

(Figure 2). Essentially, the Introduction puts your study into context. For example, if your

research evaluated the efficacy of a treatment for triple-negative breast cancer (TNBC)

liver metastasis, you would briefly introduce TNBC, incidences of metastasis, and the

efficacy of current treatments. Next, you should highlight an important problem in the

field; in this example, the limited treatment options for TNBC that has metastasized to the

liver. This will then lead to your objectives—how does your study aim to address this

problem? A properly structured Introduction will make it clear to the reader why your

study needed to be done and why your study is clinically relevant.

During peer review, one of the most critically evaluated sections of your manuscript is the

Methods section. Therefore, it is important to objectively and accurately describe patient

information and enrollment details, your study design (including controls), interventions

used, and statistical analyses applied. Poor descriptions of these elements will usually

lead to the reviewers returning the manuscript to you for clarification.

Presenting your results in a logical manner is essential. If you conducted a randomized

clinical trial (RCT), including a flowchart that illustrates the flow of patients through the

trial, such as that provided by CONSORT (Consolidated Standards of Reporting Trials)

[5], is helpful in making an informed analysis of the course of treatment. Next, the key

findings of your study should be objectively described—treatment outcomes, efficacy,

and adverse events. You should emphasize the significance of your findings and include

relevant data (e.g., p-values, confidence intervals, and odds ratios) to support these

findings.

Finally, and one of the biggest challenges for many authors, is writing a good Discussion.

Readers will often look ahead to the Discussion to obtain a summary of the findings, their

relevance for the field, and their clinical implications. The Discussion section should be

both concise and objective. After stating your major conclusion, you should then support

it by summarizing the key findings from your study and interpreting them in the context of

previously published work. This demonstrates the relevance of your findings to the

current state of knowledge. Your Discussion and ultimate conclusion should be based

only on the evidence presented, and address any alternative explanations of the data if

they exist. It is important to not be too speculative in your interpretations and to focus on

This article was originally published in Japanese in Japanese Journal of Breast Cancer 2013; 28(6):

575–580. The English version of this article has been reproduced with permission from the Japanese Journal of Breast Cancer.

the outcome based on your initial objectives. Finally, include any clinical implications and

future directions for study suggested by your research.

ETHICAL CONSIDERATIONS

In addition to the structural components of a manuscript, adherence to research and

publication ethics is crucial to your publication success. To ensure that you are

conducting your research and writing your manuscripts in accordance with the most

up-to-date ethical guidelines, there are three primary resources worth keeping on hand.

The International Committee of Medical Journal Editors (ICMJE) produces the

industry-standard guidelines for publication ethics [6]. The Good Publication Practices

(or GPP2) document [7], which provides recommendations for authors working on

company-sponsored research, should also be consulted. Finally, the Committee on

Publication Ethics (or COPE) forum [8], which provides resources and case examples for

ethical publication issues, rounds out a solid set of resources for use when preparing

studies for publication.

CONSORT and STROBE

Many journals will also ask clinical authors to submit a checklist from CONSORT [5] or

STROBE [9] upon submission of their manuscript. CONSORT is used for RCTs, while

STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) is

used for observational studies. These checklists cover the essential points needed by

journal editors and readers to properly assess your results and ethical compliance

throughout the course of the study. Even if a journal does not require that a CONSORT

or STROBE checklist is submitted, they can be a highly useful resource in manuscript

preparation and to anticipate questions that reviewers might ask. How patients were

chosen to participate in the study and what consideration was given to participants that

might be particularly susceptible to harm are issues of concern no matter what the type

of study, so working in accordance with these checklists will demonstrate that you have

followed good clinical practice for working with human subjects.

Clinical trial registration

For authors involved in clinical trials, trial registration is required as a condition of

publication for many journals. The ICMJE defines a clinical trial as “any research project

that prospectively assigns human subjects to intervention and comparison groups to

study the cause-and-effect relationship between a medical intervention and a health

outcome”, which is supported by the World Health Organization as the world standard

This article was originally published in Japanese in Japanese Journal of Breast Cancer 2013; 28(6):

575–580. The English version of this article has been reproduced with permission from the Japanese Journal of Breast Cancer.

[10,11]. Trial registration has become the standard practice in clinical research as it

allows open sharing of potentially critical data with researchers, clinicians, and patients,

and helps reduce the issue of selective reporting. The implementation of registration

requirements means that all Phase II and III trials that started enrolling patients on or

after July 1, 2005, and all Phase I studies started on or after July 1, 2008, should be

prospectively registered before publication [10,12].

Clinical trial registration needs to be done in a public database, of which popular options

include Clinicaltrials.gov (http://clinicaltrials.gov/), JAPIC (http://www.japic.or.jp/), and

UMIN (http://www.umin.ac.jp/ctr/). Most medical journals follow the ICMJE guidelines,

and thus are very strict about only accepting trials for publication that have been

prospectively registered [13]. However, many still do accept retrospective registration in

certain cases, so if your trial is not yet registered, it is worth enquiring whether your target

journal will accept late registration and if a rationale for the delay is required [14].

Plagiarism

Finally, with the strong increase in recent years of rejections and retractions for

plagiarism [15], close analysis of the use of references and your own previously

published work is needed. Copying of any previously published material, whether it is

your own work or unintentional, is considered unethical, and with the increase in number

of journals now using plagiarism detection software such as iThenticate (CrossCheck), it

is unlikely to go unnoticed.

CONCLUSION

In summary, sharing your work with an international audience and having your results

published in the most appropriate journal are the primary goals of manuscript publication.

To do so effectively, it is essential as an author to be aware of the structural and content

requirements for your manuscript, as well as the ethical guidelines underlying your

research and how it is shared with the public. Active involvement and awareness of the

publishing process will ensure you end up with a well-written and ethically sound

manuscript that has a greater chance of acceptance.

This article was originally published in Japanese in Japanese Journal of Breast Cancer 2013; 28(6):

575–580. The English version of this article has been reproduced with permission from the Japanese Journal of Breast Cancer.

REFERENCES

1. Verma S, Miles D, Gianni L, et al: Trastuzumab emtansine for HER2-positive advanced

breast cancer. N Engl J Med 367:1783-1791, 2012.

2. Mayor S: BMJ and Lancet rank among the most clinically relevant medical journals. BMJ

329:592.6, 2004.

3. McKibbon KA, Wilczynski NL, Haynes RB: What do evidence-based secondary journals tell

us about the publication of clinically important articles in primary healthcare journals? BMC

Med 2:33, 2004.

4. Gopen GD, Swan JA: The science of scientific writing. Am Scientist 78:550-558, 1990.

5. Schulz KF, Altman DG, Moher D, for the CONSORT Group: CONSORT 2010 Statement:

updated guidelines for reporting parallel group randomized trials. BMJ 340:c332, 2010.

6. International Committee of Medical Journal Editors. Recommendations for the conduct,

reporting, editing, and publication of scholarly work in medical journals. Updated August 2013.

http://www.icmje.org/urm_main.html. Accessed September 24, 2013.

7. Graf C, Battisti WP, Bridges D, et al: Good publication practice for communicating company

sponsored medical research: the GPP2 guidelines. BMJ 339:b4330, 2009.

8. Committee on Publication Ethics: http://publicationethics.org/. Accessed September 24,

2013.

9. von Elm E, Altman DG, Egger M, et al; STROBE Initiative: The strengthening the reporting of

observational studies in epidemiology (STROBE) statement: guidelines for reporting

observational studies. J Clin Epidemiol 61:344-349, 2008.

10. International Committee of Medical Journal Editors: Clinical trial registration: A statement

from the International Committee of Medical Journal Editors. [Editorial]. September 2004.

11. World Health Organization: International Clinical Trials Registry Platform.

http://www.who.int/ictrp/about/details/en/index.html. Accessed September 24, 2013.

12. International Committee of Medical Journal Editors. Clinical trial registration: Looking back

and moving ahead. June 2007. http://www.icmje.org/update_june07.html. Accessed

September 24, 2013.

13. Haller DG: Clinical trials registration: Will your study be publishable? J Clin Oncol 27:1, 2009.

14. Barbour V: Full Registration and reporting of all trials at PLOS Medicine. PLOS Blogs August

13, 2013.

http://blogs.plos.org/speakingofmedicine/2013/08/13/full-registration-and-reporting-of-all-trial

s-at-plos-medicine/. Accessed September 24, 2013.

15. iThenticate. Rising tide of plagiarism and misconduct in medical research. 2013 iThenticate

Paper.