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A Guide for Clinical Research

Version December 9, 2011

Jerrold H. Levy, MD, FAHA
Professor and Deputy Chair for Research
EmoryUniversitySchool of Medicine
Emory Healthcare Atlanta, Georgia

I.    Defining Your Study Idea

Developing a study idea that is destined for success is based on two important steps: 1) generating the study idea and 2) refining the study question(s). This step will discuss these concepts allowing you to develop a plan that you can apply to the case scenarios in this portal or to your individual study idea.

a.    Refining your study idea
b.    Literature Search
c.    Sample Size
d.    Research Team
e.    Funding Mechanisms
f.    Timeline
g.    Scope
h.    Ethical considerations
i.    Summary

The first step in conducting a research study is to take an idea and narrow it down to a concrete, researchable issue. In determining if your initial research idea is answerable, you must ask yourself the question, “Is my research idea doable the way I’m currently proposing it”. Put another way, you might ask, “Can I force a square peg through this round hole?” In order to make progress, this question must be honestly answered. Bouncing ideas off mentors and colleagues best facilitates this. Walt Disney was a very successful facilitator of creative ideas.

There are four main factors to consider when generating the study idea or clinical question. A simple way to help you frame a clinical question is to use the acronym PICO (Patients, Intervention, Comparison, and Outcome) as noted below.
 
Summary of PICO



Method
Therapeutic
Prognostic
Diagnostic

Patients
What patient group?
What patient group?
What patient group?

Intervention or procedure    What surgical procedure or implant?    What factors might influence outcome?    What diagnostic procedure?
Comparison
What treatment is being compared?    What factors might influence outcome?
Is there a gold standard?

Outcomes
In what outcomes are you interested?    In what outcomes are you interested?    Are you interested in validity, reliability, or both?

1) Patients
It is important to define the patient population of interest not only to perform an efficient literature search, but also to arrive at the appropriate answers. Specifically, one must consider patient characteristics that may affect outcome such as:

Intervention or procedure
Treatment
Sex
Age
General Health
Medical History
Concomitant Medications

2) Intervention or procedure
How you include this factor in your clinical question depends on what you are interested in:
1.    Therapy (treatment)- define the intervention in which you are interested (e.g. a new implant or new surgical technique)
2.    Prognosis (the ability to predict an outcome) – define factors that may influence outcome (e.g. smoking status or age)
3.    Diagnosis (the value of a diagnostic test) – define the diagnostic procedure of interest (e.g. a new technology)

3) Comparison group(s)
You must define the “control” group to which the intervention group will be compared. Some times your question will not have a control group, such as in the case where you are interested in safety or handling characteristics of new implant or procedure.

4) Outcome(s)
Here you must decide on what outcomes are important to your question. Here it is good to be specific and to aim for the most important outcomes. Examples include nonunion, major complications, repeat surgery, quality-of-life, or death.

a. Refining your study idea
The key to a successful clinical study is to ask an answerable question. This seems obvious but all too often one develops a great hypothesis or idea that cannot be answered. Once a research idea has been developed, it needs to be translated into an appropriate study question. It is important to consider the novelty, feasibility, and ethics of the study question early in the stages of development to ensure that the project will succeed. Several important considerations are outlined in table 1 and described in more detail below.






Table 1.1  Important issues to consider when refining your study question.


Consideration
Ways to address it
Ways to deal with it

Is this study novel?
Conduct a literature search of your topic in PUBMED, and search the CRISP database for NIH funded grants (or other governmental database) in your topic area.    Modify the study question to include some novel aspect.

Can I enroll enough willing, consenting participants meeting my inclusion criteria to make meaningful inferences?    Analyze data from (or critically review results of) previous studies for participations rates and prevalence of outcomes and treatments of interest. Also, do sample size calculations     Broaden inclusion criteria or length of enrollment to increase sample size.
Does my team of collaborators have adequate expertise to carry out this research?    Schedule meetings with study collaborators during the early stages of study planning to identify potential gaps in knowledge or skills.
Seek outside consulting.
Do I have enough financial support to address this study question adequately?    Draft a budget plan.
Apply for funding.

Do I have the time to see this study from start to finish?    Draft a timeline.
Consider an alternative study design.

Is the scope of this study manageable?    Write down and discuss your specific aims with study collaborators.
Modify the aims, retains those that are most significant.
Is this study ethical?
Discuss with your collaborators, and submit an application to the human subjects review board at your institution.    Modify the study question, or study design.


b. Literature Search
An important first step in developing the study question is to conduct a critical review of the pertinent literature. Special attention should be given to identify gaps in the literature that the incipient study will attempt to fill. PUBMED is a search engine containing titles and citations on most health-related literature published in many U.S. based and international journals. The majority of these include abstracts and links to full text articles. In addition to keyword searches, publication date, journal title, contributing author(s), study design, and more [Pubmed.com] can limit PUBMED searches.

In addition to identifying novel aspects of a study question, a review of the pertinent literature may also help the investigator to identify factors, which may confound or complicate the study question. This information may play a role in selecting the type of study design (matched versus unmatched, simple randomization versus block-randomized, etc.), study population, and in the development of study instruments such as questionnaires. For example, if one is interested in studying the functional outcomes associated with amputation versus lower limb reconstruction for high energy tibial fractures in a non-randomized study, it may be advisable to restrict the population under study to patients of a certain class of injury, since the literature indicates that injury severity often dictates the type of treatment for these fractures and is clearly linked to functional outcomes.

c. Sample Size
Sample size is an important consideration at this stage of study development, and will depend on factors such as the study design, the prevalence of the outcome and treatment of interest, and the estimated size of effect. It is advisable to at least do some rough calculations this early in the process to try and determine the potential size of your study and how that might influence refining your study questions.

d. Research Team
Depending on the scope of the project, the research team can be small (consisting of the investigator and a mentor) or relatively large (consisting of additional collaborators from other disciplines such as biostatistics and medical specialties). In addition to the key collaborators, the research team may also incorporate study staff such as a study manager, interviewer, data analyst, and fiscal administrator.

e. Funding Mechanisms

There are four main mechanisms for obtaining funding for a research study:

•    Intramural support from your own institution
•    Governmental agencies
•    Not-for-profit institutions
•    Industry sponsors
•    Intramural support

If you determine that additional funding is needed to address the study question, you should begin by inquiring about any intramural support available, but we can discuss that. There are applications procedures for small starter grants.

Governmental agencies

A good starting place to investigate sources of governmental funding for research is your country’s department of public health or ministry of health. In some cases, these institutes provide research funding; in other cases they provide links for such funding mechanisms.

The National Institutes of Health (NIH) is a governmental institute that funds the greatest amount of health-related research in the U.S. The 27 centers and institutes that comprise the NIH focus on a variety of health topics. The NIH offers several types of grants, and applications are due at specific times in the year. Some common investigator initiated grants include the R01 and R03, which can be applied to the widest variety of research topics. Requests for applications (RFAs) and requests for proposals (RFPs) are initiated by the NIH for specific topic areas that the agency determines to be important at the time they were initiated.

Other sources for funding include companies that may be interested in the device or pharmacologic agent you wish to investigate. If so, it would be worthwhile to contact the sponsor to inquire about funding, something that I can help you with. You may have contact through a sales representative but that is not necessary. The key to getting funding from a sponsor is a well-developed study protocol that will gain their confidence and get them interested. However, it is worthwhile to make initial contact to seek interest prior to completing the protocol. Funding can be as small as monies sufficient to purchase some capital equipment like a computer or as large as is necessary to hire research assistants and additional consultants to complete a large prospective study.

f. Timeline
Before beginning a study, it is important to create an estimated and realistic timeline, which outlines the important aspects of the study that is agreed upon by all collaborators involved. Sufficient time should be allotted for pre-study preparations, data collection, laboratory analysis (if any), and data analysis. It will be important to stay on target during the study, particularly when the funding period is defined and limited (such as with most grants). A more detailed look at timeline necessary for study protocol development will be presented in the next section.

g.Scope
Once your study question has been refined, the final step in developing your study idea is to write the specific aims. The aims of a study should be specific and hypothesis driven. It is common for a study to have between 2 and 4 specific aims, which are components of an overarching research question.  It is common to have one or two primary questions that you would like to answer and another one or two secondary questions you would be interested in exploring.  Those questions that are of primary interest are commonly considered primary aims.  The rest of your protocol is centered on your primary aims including your sample size calculations and data analysis. It will be necessary that you have adequate power (i.e. a large enough sample size) to answer the primary aims. On the other hand, you do not necessarily need to power your study to answer your secondary aims. Therefore, it is recommended that questions that are of secondary interest or may require a sample size that you can’t obtain should be secondary aims.

The secondary aims are designed to assess long-term outcomes, or other secondary endpoints.




h. Ethical considerations
Several ethical considerations should be made in the early stages of developing the study question. For a randomized control trial, several obvious questions should be asked including:

•    Is there reason to believe that the treatment under study will be more effective compared with standard care, yet reasonably uncertain to justify the study?
•    Is it ethical to randomize patients to their treatment, or are there other considerations that should play a role in their treatment choice?
•    Is it ethical to blind a patient or health care provider from his/her treatment?
•    Less obvious ethical questions exist for observational studies. As with all studies, it is important to protect the privacy of the study participants with respect to health records. The number of study staff accessing personal identifying information should be kept to a minimum.
•    At this early stage of the study, it is important to discuss these ethical issues, but as the study begins to develop and a more concrete study plan takes form, a formal application will need to be submitted to the Institutional Review Board (IRB) at your institution. The IRB exists to protect participants involved in research. A more detailed description of the IRB process is provided in Step 2.

j.    Summary
The preceding paragraphs describe the key points in developing a study idea. Briefly, the study idea often results from dialogue with mentors and colleagues facilitated through several types of organized discussion sessions. At this early stage of development, it is also important to begin to identify the type of study question you are interested in answering (i.e. diagnostic, therapeutic, prognostic, or economic), as well as the patient group, comparison of interest, and outcome of interest for your study. Once this basic groundwork has been laid, more deeply considering the novelty, feasibility, and ethics of the study best facilitates refining the study question. This is where you should begin to think about such things as conducting a detailed literature search, doing some initial sample size calculations, creating a team of collaborators, applying for funding, drafting a timeline, writing a draft of your specific aims, and when you will submit an application to the IRB. The final step in developing the study idea is to finalize the specific aims of your study. These aims will provide the cornerstone for your study plan.

II.    Stages of development

A.    Developing the study plan

Once the study question and specific aims have been established, you can begin developing your study plan. The study plan is best developed in three stages with each subsequent stage increasing in complexity as outlined below.
Stage 1
Stage 2
Stage 3

Study Outline
Study Protocol
Study operations manual

 
A.    Stage 1: Study outline or letter of intent (LOI)
The purpose is to provide an outline of the basic elements of the proposed study, and should be one to two pages in length. The basic components for this outline are listed below (Table 2.1):

Table 2.1. Checklist for LOI

1
Research Question
X

2
Background and Significance
X

3
Expected outcomes
X

4
Time frame
X

5
Methods and brief research plan
Study design
Subject inclusion and exclusion criteria
Demographic, predictor, and outcome variables
Statistical issues (hypotheses, sample size, basic analysis plan)    X

6
Participants
X

7
Resources and budget
X

8
Research site
X

 
The study plan and one- to two-page outline should be written out at an early stage using the checklist. Putting ideas on paper is an important step in facilitating discussions and advice from colleagues or mentors. For many, this is a challenge as it is easier to talk about an idea than to write it down; however, it will certainly lead to a faster start and improved study.  Table 2.2 provides an example of a study outline.

Table 2.2. Example outline of a study (LOI).

Element
Example

1.    Research Question    Can recombinant activated Factor VIIa (rFVIIa)-induced facilitation of thrombin generation acutely reverse Clopidogrel in vitro? Or what is the in vitro effect….
2.    Background and Significance   
Antiplatelet therapy with Plavix (Clopidogrel) is an integral part of therapy in patients in the cardiac catheterization laboratory and for long-term management of atherosclerotic cardiovascular disease. The effects of antiplatelet agents are, in part, attributed to the reduction of thrombin formation in diseased coronary lesionsThis can pose a problem of excessive bleeding if a patient on Clopidogrel therapy presents for cardiac surgery,Currently, there are no pharmacological agents available for the attenuation of Clopidogrel antiplatelet effectsRecombinant factor VIIa (FVIIa- NovoSeven) is an activated coagulation factor that is FDA approved for the treatment of hemophilia.4FVIIa dose binds to the surface of activated platelets increasing thrombin generation.Preliminary laboratory data from our lab suggest FVIIa offers a potential mechanism to reverse most platelet disorders.

3.    Expected outcomes   
Unknown? Or it is anticipated that rFVIIa induced facilitation of thrombin generation CAN acutely reverse Clopidogrel.
Few comparison studies with sound study methods exist making this comparison.
4.    Time frame   
3-month ramp up.
12-month recruitment, follow-up, and data collection.
3-month closeout.
Methods and brief research plan
Study design

5.    Subject inclusion and exclusion criteria
Demographic, predictor, and outcome variables
Statistical issues (hypotheses, sample size, basic analysis plan)    Design:
Single site, prospective in-vitro study
Subject criteria:
20 Male and female adult patients undergoing PCI,on Clopidogrel therapy

18 years or older, able to provide informed consent; excluded if known preexisting hemostatic abnormality, pregnancy, concurrent participation in a trial of investigational drug or device

 20 ml blood samples will be collected from 20 consented patients To evaluate the effects of Clopidogrel and Novo Seven on thrombin generation in PRP, a calibrated automated thrombography system will be used (Biodis, Signes, France). Thrombin generation parameters, i.e. lag time, peak thrombin and endogenous thrombin potential will be determined utilizing the Thrombinoscope software (ThrombinoscopeTM , Maastricht, The Netherlands).Statistical issues: analysis will be conducted with SPSS 15.0 using the paired t-test or the repeated measures analysis of variance, followed by paired t-test with the Bonferroni correction

6.    Participants    List co-investigators andcollaborators involved in the study.

7.    Resources and budget    An estimate of costs for study personnel, laboratory supplies, institutional costs, subject payments, data analysis, publishing and consulting costs if applicable.
8.    Research site    Explanation of institution(s) where patients will be recruited and primary data will be collected and managed.
 

B.    Stage 2: Study protocol

This is an extended version of the outline, which should contain as much detail as possible, Table 2.3. This protocol provides the main framework for the study justification and operations. It will be submitted to the institutional review board (IRB) and any sponsor or future grant applications if applicable. A copy will be maintained in the study operations manual.

Table 2.3 Outline for a study protocol.
Element
PURPOSE

1. Specific aim (s)
What aims will the study address?

2. Background and significance    What is known about the subject and why are these aims important?

3. Methods


a. Study design
What study design will best answer the question given the various limitations?
b. Subjects
 Selection criteria
 Sampling    Who are the subjects that are to be included?
How will the subjects be selected & recruited?
c. Intervention
What is the treatment or intervention?

d. Patient enrollment and data
 collection    How will patients be recruited and enrolled?
How will data be collected?
e. Measurements
    Predictor variables
    Potential confounding
    variables
    Outcome variables    Explanation of institution(s) where patients will be recruited and primary data will be collected and managed.
f. Quality control and data
    management
    Compliance
    Follow-up    Explanation of institution(s) where patients will be recruited and primary data will be collected and managed.
4. Statistical Issues
Sample size
What analysis will I do?    How large will the study need to be?
How will the data be analyzed?
5. Timetables and organization    What is the timeframe for starting and finishing the clinical trial?

6. Ethical considerations
Safety, privacy & confidentiality
Informed Consent/Institutional Review
    How will safety, privacy and confidentiality be handled?

Writing the Protocol INTRODUCTION:
You can borrow from your Background and Significance section of your protocol when you write this section. It will be important to be relatively brief, likely far fewer characters than your protocol. The key is to inform the reader as to why your topic is important. It is not necessary to spend a tremendous amount of effort reiterating what others have already discussed in previous studies on your topic. Try to make it novel and to the point. The introduction should end with a clear and concise description of your study purpose. If you had more than one purpose or a secondary purpose, list them separately.

C.    Stage 3. Keeping Records: Study Operations Manual (Regulatory Binder)

When performing a company sponsored clinical trial, there are a series of documents that you are required to keep as will be described in subsequent comments.  If you are performing an investigator sponsored trial, then you should plan on storing your own documents for evaluation purposes, and in case there are issues at a later time, particulary if you are trying to publish your results.

The Study Operations Manual (Regulatory Binder)These documents serve to demonstrate compliance with standards of Good Clinical Practice and with all applicable regulatory requirements. The purpose is to also provide detailed instructions for all study procedures. This manual should include the step-by-step process for enrolling and following patients, entering and managing data, and monitoring the process.  Copies of all study materials, including study protocol, consent forms, questionnaires, etc, should also be included in the manual. The Regulatory Binder is often the first document reviewed during pharmaceutical company and/or FDA audits and inspections (see link http://www.fda.gov/ICECI/Inspections/InspectionGuides/default.htm).  Procedures for maintaining confidentiality and quality assurance and control should also be covered, and information can be found at http://www.fda.gov/downloads/regulatoryinformation/guidances/ucm129515.pdf.

III.    Study Analysis and Reporting

Once you have developed your study idea, developed your study plan, and executed your study successfully, the fun part begins! Now is the time to discover the truth behind your study questions. Is treatment A better than treatment B? Does it depend on what group of patients received the treatment (e.g., young versus old)? Are patients really better off receiving this new plate or surgical technique? Is it possible that the old way is the best way? Is it possible that it doesn’t matter what technique you use? Finding out these answers is the motivating force behind performing a clinical study. If you paid attention to detail in your study planning and worked hard in ensuring the quality and validity of your data collection methods, there is no reason these questions cannot be answered, at least in your study population.
Many investigators reach this point in the study so exhausted that they put the data aside and forget about it for a while. It’s not uncommon to leave such a tremendous effort behind by not getting to the data analysis.  Discipline in sticking to the effort until the end is paramount for this phase of your study. Unfortunately, we cannot just push a button and all our results, tables, and figures pop up on our computer screen. Performing the data analysis takes a combination of expertise, discipline, and patience in carefully handling the data in accordance with the data analysis plan you set forth in the study protocol. This goes back to assembling a complete research team. Though resources may limit you, it pays to get an epidemiologist or biostatistician involved in this phase of your study, if even as a consultant. Ideally, this person was involved in helping you develop the analysis plan in the protocol. They can help you with basic elements of the data analysis to be sure you are handling your data in an efficient and effective manner.  Furthermore, if available to you, they can perform the whole analysis in a complete and robust manner, which will get the best out of your hard efforts up to this point. On the other hand, some investigators enjoy analyzing their own data and have the expertise to do it. If so, go for it! If not, you can learn a lot by working along side a person who does the analysis for or with you.

Like we did previously where we discussed study design principles following the outline of a protocol, we will discuss data analysis and reporting principles following the outline of a study report or manuscript for publication. Keep in mind that each sponsor (if applicable) and journal may have different requirements and therefore the outline may change slightly; however, these basic elements should be included in any study report or manuscript for publication.


There is a tendency to change your objectives based on findings you have become aware of since the study. Be careful with this. It is OK to report secondary findings that you did not anticipate, but it is important that they are reported in their context and not as primary objectives. Bottom line - list the objectives you set out to answer. They should be consistent with the specific aims from your protocol. Statistically non-significant findings are still “significant”!

Methods
This is where you tell your reader what study design you chose to use to answer your primary and secondary objectives. It also gives you the opportunity to describe the institution(s) in which you recruited your subjects.  You get to tell your story of how you identified and recruited subjects, the characteristics of these subjects, how many participated and how many you lost to follow-up.

Study design
This section is short and to the point. Here you tell the reader whether your study was a randomized or quasi-randomized controlled trial, cohort study, case-control study, case-series and whether you used additional methods such as matching, block randomization, stratified randomization, etc.

Subjects
It is very important to clearly and thoroughly describe your study populations. Readers need to know if your results and conclusions may be generalized to their population. Additionally, it is important to place your study in time. Technological advances, changes in patient care procedures, and differences in reporting practices at different times can affect the outcomes and interpretation of your study1. The following items should be included in this section:

•    Explanation of inclusion and exclusion criteria.
•    Institutions in which you identified and recruited your patients.
•    Time period in which you collected your data.
•    For retrospective studies, give the dates during which the data were originally collected as opposed to when you abstracted them from the study.

Data collection
It is important in this section to describe clearly and concisely the process by which you identified and recruited subjects and whether they finished the study. Full accountability of every subject should be attempted. When possible, provide a schematic summary of the study showing the number and disposition of participants at each stage, Figure 11.1.

The schematic summary should include:
•    The total number of subjects approached.
•    The total number of subjects found eligible and ineligible.
•    The number of subjects who agreed to participate and signed informed consent.
•    The number of subjects who did not complete the study (e.g., lost to follow-up, withdrew, died).
•    The number of subjects who completed the study and whose data are included in the final analysis.
Make every attempt to describe the following subjects:
•    Those evaluated who did not meet the study criteria.
•    Those subjects who were approached but declined to participate.
•    Those subjects who were enrolled but were withdrawn or “dropped out”.
•    Those subjects who were enrolled but were lost to follow-up.
•    Those subjects who were enrolled and completed the study.

Subjects who agree to participate may differ in important ways than those who decline to participate. For example, they may be more likely to take risks or more motivated to get better and comply with the treatment protocol.  Patients may be withdrawn or “drop out” willingly for various reasons, some of which may bias the interpretation of the results. Subjects who are lost to follow-up may be those subjects who are least satisfied with the results of their treatment or may be doing so well they do not feel they need to be evaluated any longer. Either scenario could bias the results. Studies with low follow-up rates (i.e., <90%) should be interpreted cautiously for this reason. Finally, the final sample should be described completely. This is generally done in the results section.

Describe the nature and duration of follow-up effort. This should come directly from your protocol assuming you followed these procedures. For example, you may state something like this:
Upon study entry, we obtained the following:
•    Patients mailing address, telephone number, and E-mail address.
•    The name and address of their primary care physician.
•    The name, address and phone number of three people at different addresses with whom the patient does not live who are likely to be aware of the patient’s location.
•    Study personnel called patients to remind them of upcoming study visits and patients were contacted no less frequently than once every three months to maintain contact and planned change in residence.

Finally, describe the baseline prognostic factors and outcome measures that were collected. If special instruments were used to define these, identify them, provide any background info as to their validity, reliability, and responsiveness, and if possible provide a copy of the instrument in the paper. A clear description of the instrument’s content, scale, and interpretation with appropriate references should be included whether you provide an actual copy of the instrument or not.

Data analysis

The Uniform Requirements for Manuscripts Submitted to Biomedical Journals summarizes the overall intent of statistical reporting: “Describe statistical methods with enough detail to enable a knowledgeable reader with access to the original data to verify the reported results”2.

The statistical comparisons you make here are the same as the ones you specified in your protocol before any data were collected1. Therefore, this section should restate what that plan was. Assuming you followed that plan, this section can be a mirror image of the protocol’s section with some slight edits as needed. It is understandable that the choice of specific statistical tests may depend on the quality of the data in the end (e.g., whether continuous data were normally distributed or not), so the specific test often cannot be stated in advance. In the end, this section should provide a clear and concise description of how you analyzed your data so that someone could repeat it. If you performed a randomized controlled trial, you should be clear as to whether the statistical analysis was on the basis of intent-to-treat. Furthermore, it is a good idea to reiterate you power calculations so as to validate whether or not you achieved the necessary number of patients in your study that you had planned for. Finally, identify the statistical package or program (with its corresponding reference) used to analyze the data. Results may very slightly from package to package due to discrepancies in validation and updating.

Results
The results section should be quick and to the point. In other words, there should not be too much explaining or justifying the findings. This is left for the discussion. The flow of the results section should begin with descriptive statistics of study groups, findings with respect to measured risk factors or outcomes (analytical statistics) and accompanying tables and figures as necessary.

Descriptive statistics
The presentation of descriptive data on the study population is important for the following reasons:
It enables you to determine the comparability of study groups at baseline and evaluate the likelihood of any selection bias or confounding.
The baseline characteristics of the study population can help in determining the generalizability of the results of study population to other study populations.

IV.    Submitting For Publication

You have come to the end of a long journey. The study was conceived, planned, executed, analyzed and reports have been written. You have spent a significant amount of time writing your reports in a typical journal manuscript format. Now it is time to select a journal and submit your manuscript for publication. It is only through publication that you will be able to help change or improve the way orthopedic surgery is performed today. Whether your results are what you expected or wanted, publishing is very important. Avoid the temptation to not submit results that are negative or counter to your hypothesis. This is known as publication bias.

Before submitting for publication, it is important to have your peers review your manuscript. In fact, it is not a bad idea to have multiple people review it as you develop it. For example, you may want to have your methods section reviewed before you write up the results. Changes in your methods section will undoubtedly affect the way you report the results. Expect this process to be lengthy. Time spent having your colleagues review your paper is time saved when you submit it to a journal. It may even be the difference between acceptance and rejection. An important point to make along these lines: if you are asking colleagues to review your manuscripts (whether they are co-authors or not), be sure to return the favor.

The following are some important principles that you should consider when submitting your manuscript for publications:
1. Select a journal that is most appropriate for the audience you want to reach.
This may be intuitive to you if you are comfortable with the literature.
You may want to look at past journals tables of contents and visit the website of specific journals to determine their mission and interests.
2. Consider writing to the editor of one or more journals to determine whether or not they are interested in publishing your topic.
This is not a requirement and you may not get an answer; however, it doesn’t hurt to try and may save you some time in the long run.
3. Make sure that you adhere strictly to the guidelines of formatting and submission of the selected journal.
Every journal is different. Sometimes the differences are obvious and other times subtle.
Print the guidelines from the website and use it as a checklist. Go over it several times.
4. If rejected, don’t be discouraged.
Your clinical question may not meet the interests or needs of the journal you are submitting to. In these cases, it doesn’t matter how good your manuscript is.
If you are not given the opportunity to re-submit, accept this decision and move on to another journal.
5. Expect criticism and improve your paper accordingly.
No manuscript is returned without criticism and editing.
It is not uncommon to receive lots of criticism and even be asked to re-analyze your data a different way.
Be objective, talk to colleagues, and decide if the criticisms are warranted. Most of the time they are. Try and appease the reviewer; however, don’t compromise the intent of your study.
6. Don’t be afraid to argue your case.
It is not uncommon for a reviewer to misinterpret or misunderstand your findings. After all, they are humans too.
If you feel this has happened, just respond with a clear and concise explanation. You may need to augment your argument with more data or slight adjustments to your manuscript for clarification.
7. Persevere and be patient.
The time that elapses from when you submit your manuscript to when it is actually printed may be several months.
Consider this part of the process and continue on with more research!

References
Vance M and D D: Ideation techniques: Think Out of the Box. FranklinLakes, NJ, Career Press, 1995, pp 155-170.
Koepsell TD and WeissNS: Overview of Study Designs: In: Epidemiologic Methods: Studying the Occurrence of Illness. New York, Oxford University Press, Inc., 2003, pp 93-115.
Koepsell TD and WeissNS: Randomized Trials: In: Epidemiologic Methods: Studying the Occurrence of Illness. New York, Oxford University Press, Inc., 2003, pp 308-45.
Koepsell TD and WeissNS: Cohort Studies: In: Epidemiologic Methods: Studying the Occurrence of Illness. New York, Oxford University Press, Inc., 2003, pp 346-73.
Hulley SB, Cummings SR, Browner WS, Grady Deborah, Hearst N and TB N: DesigningClinical Research. Philadelphia, PA, Lippincott Williams and Wilkins, 2001, pp 336.
Slevin ML, Plant H, Lynch D, Drinkwater J and Gregory WM: Who should measure quality of life, the doctor or the patient? Br J Cancer. 57: 109-12, 1988.
Byrne M: Cancer chemotherapy and quality of life. Bmj. 304: 1523-4, 1992.
Norris D: Clinical Research Coordinator Handbook. Medford, New Jersey, Plexus Publishing, Inc., 2001.

Last updated on Tue, 17 Jan 2012