Clinical research original article: How to write an article and get it published in European Urology Shahrokh F. Shariat, MD Chair and Professor, Medical University of Vienna, Vienna, AUT Adjunct Professor, Weill Cornell Medical University and New York Presbyterian Hospital, New York, USA Adjunct Professor of Urology, UT Southwestern, Dallas, Texas, USA

Remember the purpose of your manuscript …is to inform Introduction Materials & Methods Results Discussion Conclusions

Introduction Materials & Methods Results Discussion Conclusions A single piece of work Keep it joined together One section should flow into the next NO SURPRISES

Clearly and simply explain –what the research question is –why it is relevant, why it is original –very briefly how it will be answered Introduction section

Summarize other relevant papers in orderly fashion (logic) to set the background –Not be an in-depth literature review Introduction section

An excellent study has an obviously important and original question, and therefore needs only brief introduction. –Make it short: words, ~3-4 paragraphs, 1 page Introduction section

1 st paragraph: brief background in present tense to establish context, relevance, or nature of the problem, question, or purpose (what we know) 2 nd paragraph: importance of the problem and unclear issues (what we do not know - gap in knowledge - why it is important to fill that gap) 3 rd paragraph: rationale, hypothesis, main objective, or purpose (why the study was done - hypothesis for how you will fill that gap in knowledge). Introduction section

1 st paragraph: brief background on radical cystectomy and role of lymph node dissection

Introduction section 2 nd paragraph: importance of the problem and unclear issues (minimal number of LN to remove, anatomical extent of LND, role of pT stage as predictor of LN involvement) 3 rd paragraph: rationale, hypothesis, main objective

Usually not easy for inexperienced authors Writing intro last can prevent writer’s block and is easier Introduction section

M&M section is the core of each paper Describes - study design, - how it was performed, and - data analysis Provides all elements to allow others to reproduce the study Easiest part of manuscript Writing this section of the paper in the most complete way before starting the study can help to discover methodological biases in a moment when they are easily fixed! Methods section

Period of enrolment/evaluation Type of study (retrospective; prospective; controlled; randomized) Inclusion criteria / patient selection Exclusion criteria / reasons to exclude patients Details on used materials or technique - report in detail original methods/techniques - cite (and reference) known methods Ethical issues What methods section should include

Methods section in RCT – Consolidated Standards of Reporting Trials (CONSORT) statement

Methods section in RCT – CONSORT statement

Methods section IRB approval Quality control Inclusion/exclusion criteria Description of pathology procedure Clinical setting TNM staging system

Study results - by definition, they go in the “Results” section Comments - on patients characteristics, indications, inclusion and exclusion criteria  they go in the “Discussion” section What methods section should NOT include

Results Describe final population Patient details Describe intervention Treatments Observations Describe outcomes Survival Disease related Toxicities Others

Discussion Summarize your main findings Compare your data with previous reports Describe & explain discrepancies Where do your findings sit in our world Where are they going to take us What next …. Limitations and concerns Final conclusions The discussion should place your findings into the scientific literature

Results: General design Patient population(s) Treatment(s) received Outcomes in each group Good and Bad findings Comparisons between groups Analysis of each factor/predictive features

Results – Using figures and tables Text Tables Figures

Text Tables Figures They should integrate together Need all three components to understand the paper But … a reader should be able to follow paper using just tables and figures So … make the legends descriptive and include all necessary findings Results – Using figures and tables

Results Be clear about your study ….. what is it? Observational Retrospective or prospective Single or Multi-institutional Data quality Screening Randomized or other Whilst Result organization is broadly similar... each may require different reporting details

Results CONSORT Guidelines = A good place to start - Participant flow Initial participants Final participants Typically Table 1. = Details of participants Figure 1. = Flow chart - What time period? Consecutive or selected patients Filtered cases or “all comers” - Institutions –How many from each? Why excluded?

Table 1. Details of patients and treatments The purpose of this table is to allow a reader to use your data: Clinicians: 1.Do the cases represent the disease? 2.Are the patients the same as mine? 3.Can I identify how to treat a patient in clinic? Researchers: 1.Can I use your data to compare with my results 2.Can I incorporate these into a meta-analysis 3.Can I use these data for new research? Patients: 1.Have I been treated correctly? 2.Is there a better doctor for me?

How to report data? Continuous data e.g. Age, PSA …. Show range, distribution and variability Mean and standard deviation, if normally distributed Median and ranges (25th and 75th centiles), if not Ordinal or nominal data e.g. stage or grade Treat as individuals (not as continuous data) Shown number and proportions for each Compare populations, if relevant Are the patients or the disease the same in each arm?

Figure 1. Flow chart of patients/studies/interventions Keep it as simple as possible

Results: Outcomes - reporting and analysis In general: -The results should match the primary and secondary outcomes (as stated in M&M) -Use paragraphs/sections for each outcome -Intention to treat analysis is more robust (as it avoids bias of losses or excluded cases)

Methods Results

Methods Results

Results: Outcomes - reporting and analysis Report outcomes for each arm/population Table 2. typically report appropriate details (mean/median & St. Dev or Ranges) Use confidence intervals (95% CI)

Results – Survival outcomes Be precise …. 1.Are you describing death or survival Disease specific survival vs. Disease specific mortality 2.What are you describing? Overall survival (death all causes) vs. Non-disease specific survival (death from other causes) or competing mortality vs. disease specific survival

Results – Treatment outcomes Be precise …. in your terminology 1.Bladder cancer behavior Recurrence, Progression, Relapse …. 2.Prostate cancer treatment PSA recurrence – Post surgery, Post ADT, Post radiotherapy 3.Incontinence outcomes Pads, further treatment, QOL outcomes 4.etc.

Results – Treatment outcomes Be precise …. Use Objective measures where possible use of another treatment (salvage radiotherapy) worsening radiology or pathology Try to avoid clinician based outcomes “progression” or “failure” with no supporting data Use blinded outcomes where possible

Results – Treatment outcomes Be precise …. Use Important outcomes (to the patient, clinician, researcher, society, healthcare provider … )

Results – Treatment outcomes Be precise …. Use Realistic outcomes

Results – Compare outcomes: Specifics Use the appropriate test For the Data: Distribution: Normal or not Data: Continuous or interval outcomes Binary or many intervals Nominal data Beware of too few cases

Results – Compare outcomes: Specifics Use the appropriate test For the Outcome: Inter group comparisons Relative and absolute outcomes Survival analysis Competing mortality Numbers needed to treat Adjustments for trial design

Results – Compare outcomes: Specifics Use the appropriate test For the Context: Univarbiable vs. Multivariable Prognostic vs. Predictive

Results – Compare outcomes: General concepts

Statistical vs. clinical significance

Results: Further analysis Typical to look at sub-group analysis or analysis of variables in later sections Maybe the most interesting findings Again … be realistic with your data Present analyses clearly and logically Do not look for analysis where the data are missing Do not perform analysis that are not justified Keep the reader with you

Discussion Briefly summarize your findings Answer your initial question Briefly mention previous reports and compare your data these reports Explain differences – you may both be right! Place your findings into the field How important are they? How strong can your conclusions be? How does this change patient care/treatments etc.? Where next with this field/work …. Limitations and shortcomings: Be critical and open with limitations … it makes the data more believable and the paper stronger

Discussion: Common issues and faults Too long Too many points addressed Too many comparisons and in too much detail Incoherent or illogical organization Poor flow, changing directions, back and forth …. Write on paper a plan and stick to it Discussion that is not supported by the data Not addressing major inconstancies with the field Too limited discussion of weaknesses etc.

The final check 1.Do you clearly state/explain and answer your main question? 2.Have you explained the novelty and importance of this work? Is it clear for someone outside the field? 3.Rigor and presentation: We are trusting that you have done this work/reported the outcomes If you can not be bothered to present/edit/check the paper properly …. then have you really treated 2,500 men consistently ? 4.Consistency: Abstract vs. main body Tables & figures vs. main text 5.Are your conclusions justified?