Clinical research paper

Pmcid: pmc3380258how to read a clinical trial papera lesson in basic trial statisticsshail m. Medical center drive spc 5682 ann arbor, mi 48109; tel: 734-647-2964; fax: 734-763-2535; e-mail: @sniggihpauthor information ► copyright and license information ►copyright © 2012, gastro-hep communications, ctwhile the number of clinical trials performed yearly is increasing, the application of these results to individual patients is quite difficult. This article reviews key portions of the process of applying research results to clinical practice. The first step involves defining the study population and determining whether these patients are similar to the patients seen in clinical practice in terms of demographics, disease type, and disease severity. The definition of clinical response should also be scrutinized, as it may be too lenient. Clinicians should also note that statistical significance, as defined by a p-value cutoff, may be the result of a large sample size rather than a clinically significant difference. The treatment effect can be estimated by calculating the number needed to treat, which will demonstrate whether changes in clinical practice are worthwhile. Finally, this article discusses some common issues that can arise with ds: statistics, clinical trials, randomized controlled trials, outcomes, clinical researchin the last decade, the number of publications dedicated to research in gastroenterology has expanded dramatically. In parallel, the number of clinical trials has been increasing, with more than 18,000 ongoing clinical trials in the united states alone. With this rapid growth in research, clinicians find themselves trying to keep up with wave after wave of studies and trying to determine how these studies apply to their patients. As researchers learn more about disease processes, clinical trial design is also changing and becoming more complex. Medical school and subsequent clinical training provide limited education on how to evaluate these studies and incorporate their results into practice. Patients who enroll in clinical trials are usually different from the average patient with a particular disease. This trend has been well studied in oncology studies and is also a factor in gastroenterology clinical trials.

One sample was recruited from a primary care practice in the united kingdom, another was recruited from gastroenter-ologists’ offices in the united states, and the third was recruited by newspaper advertisement in the united states. 1differences in sample characteristics depend on recruitment methodin publications of clinical trials, the first table in the paper usually summarizes the characteristics of the study sample, and readers should examine this table to determine not only the age, race, and gender of the population but also the typical disease severity, disease duration, and medication history. Clinicians can only apply the results of a study to patient care if all of these factors appear to be similar to those of the patients seen in clinical happened to the subjects? This flow diagram is usually the first figure in the paper, and it shows the flow of subjects from recruitment through the end of the study (or early exit from the study). If this is the case, this finding not only validates the statistical signifi-cance of the study results but also indicates that patients consider this difference to be clinically significant. Readers may be tempted to skip the methods section of a paper, the study design should be reviewed carefully, with a particular focus on the comparator group, allocation of subjects to treatment arms, and blinding. As soon as subjects are randomized, the intention to treat them with their assigned intervention is established, even if they never receive this onally, clinical trials will be greatly damaged by a high rate of early drop out, and investigators will be tempted to present a per-protocol analysis, in which only subjects who received their assigned intervention are considered. Despite the importance of performing an itt analysis, fewer than 50% of papers in some well-regarded journals identify their analysis as an itt analysis; even among these papers, verifying that the analysis was performed correctly is difficult. Of the overlooked issues that can make a clinical trial difficult to generalize to the patients clinicians see in everyday practice is the study’s measurement of success. Clinical trials require detailed definitions of success—for example, criteria for remission or clinical response in ibd trials—and these definitions usually involve several measurements, sometimes a clinical severity index, and some form of a scale. Second issue is whether the amount of change seen in the clinical index or score is clinically meaningful to patients. Does a change of 3 points on the index presented in a published paper translate to a meaningful improvement for real-world patients? This question is important to consider, as results can be statistically significant without being clinically meaningful. Validity can have a number of meanings, but it generally includes whether the index is measuring all of the important aspects of a disease, whether it measures them accurately, whether the measurement is reproducible in subjects whose condition has not changed, and whether the instrument is responsive to small but clinically important changes.

While measuring surrogate biomarkers may appear to be an easy, inexpensive, and less invasive method of determining a clinical outcome, the validity of the surrogate markers should be scrutinized closely. Second, evidence from randomized controlled trials in other drug classes should show that improvement in the surrogate leads to an improvement in the clinical outcome. Lastly, randomized controlled trials within the same drug class should demonstrate similar improvements in the surrogate, which lead to improvements in the desired clinical outcome. For example, mucosal healing (typically defined as endoscopic healing) is often used as a surrogate marker for clinical improvement in ibd. In applying these rules, readers will notice that steroids have not led to improvements in mucosal healing despite leading to clinical improvement. However, other immunomodulators, including azathioprine, methotrexate, and infliximab (remicade, janssen biotech), have shown improvement in mucosal healing and clinical improve-ment. 17 any surrogate marker that has an inconsistent correlation with important clinical outcomes has to be viewed skeptically and should not be considered an ideal primary endpoint for clinical omous outcomes, continuous outcomes, correlations, and time-to-event endpointssome studies focus on a dichotomous outcome endpoint like clinical remission or response. For example, early studies of crohn’s disease therapies defined clinical response as a reduction in cdai score of 70 points or more, and remission was defined as an overall cdai score less than 150 points. More recently, the us food and drug administration has encouraged changing the definition of clinical response to a decrease of 100 points or more. On the other hand, when the outcome is dichotomized (hopefully into a clinically meaningful difference) and a statistically significant difference is found, these findings are more meaningful for clinical outcomes, including correlations and time-to-event endpoints (ie, time to remission), should also be treated carefully. This approach effectively counts each subject multiple times by looking at each subject at multiple time points, thus adding to the statistical power of the problem with a time-to-event analysis is that it can produce a significant p-value, but this value may not refect a clinically meaningful difference. While time-to-event analysis is considered an acceptable approach, especially in oncology, a statistically significant result with this design does not carry as much clinical weight as a statistically sig-nificant result from a t-test of a dichotomous, clinically meaningful endpoint evaluated at a single time point, given that the time-to-event analysis sets a much lower bar for enter trialsmulticenter trials offer a chance to expand the sample size in studies of rare diseases and to ensure some population diversity. Analyses of multicenter trials should always consider site as a covariate, as a few outlier sites can skew the ng target outcomessince the first gastrointestinal clinical trial, truelove and witt’s 1954 study of cortisone for the treatment of ulcer-ative colitis, target outcomes have changed and become more stringent. Called the last-observation-carried-forward approach, this method is reasonable, but it may inflate the success rates of both the primary intervention and the control arm, as a common reason patients do not return for visits is that they feel the treatment does not provide a clinical y, a third approach for addressing missing data is called imputation, in which other data are used to estimate what the missing data would have been.

Number of clinical journals and funding sources expect clinical trials to be registered on the website. Readers may also discover that some of the outcomes mentioned on the initial registration page are not reported in the published paper. A very small study will inherently have less precision, in which case a clinically meaningful effect size may be missed due to a higher p-value. The smaller study may have a larger and more clinically relevant effect, but this effect is difficult to detect with a small sample size. A meta-analysis measuring this outcome compared the clinical response in ulcerative colitis patients who were treated with 5-aminosalicylic acid drugs versus placebo, and it confirmed that the dropout rate was a powerful and intuitive way to confirm clinical response from the point of view of the patient, no matter how clinical response was measured in the study. This endpoint should be generalizable to other clinical trials and is a quick and easy way to gauge the response rate from the point of view of the example, applying this endpoint to the sonic trial, in which patients with crohn’s disease were randomized to receive azathioprine, infliximab, or combination therapy, the overall exit rate was found to be lowest in the combination therapy group. Ideally, this variability should be presented by plotting all the data points or, if the data are summarized, by showing means with 95% confidence interval bars instead of standard error or standard deviation sionwhile researchers have learned a great deal from randomized controlled trials, some hypotheses cannot be tested with prospective randomized controlled trials due to cost, duration, or ethical constraints. With this point in mind, we emphasize the importance of considering study designs beyond clinical trials, as other types of studies can address important questions that are not suited to a prospective randomized controlled trial nces1. Characteristics of patients with irritable bowel syndrome recruited from three sources: implications for clinical trials. Blinded trials taken to the test: an analysis of randomized clinical trials that report tests for the success of blinding. A review of activity indices and efficacy endpoints for clinical trials of medical therapy in adults with crohn’s disease. Voting with their feet (vwf) endpoint: a meta-analysis of an alternative endpoint in clinical trials, using 5-asa induction studies in ulcerative colitis. Medicinebookshelfdatabase of genotypes and phenotypes (dbgap)genetic testing registryinfluenza virusmap vieweronline mendelian inheritance in man (omim)pubmedpubmed central (pmc)pubmed clinical queriesrefseqgeneall genetics & medicine resources... Utilitiesjournals in ncbi databasesmesh databasencbi handbookncbi help manualncbi news & blogpubmedpubmed central (pmc)pubmed clinical queriespubmed healthall literature resources...

1999 may;5(2):g a clinical research information1department of surgery, college of medicine & asir central hospital, king khalid university, abha, saudi cta well-known unwritten law in institutions of higher learning is that of "publish or perish". The duties of a university teacher, in order of priority are teaching, research and service. Reasons for writing clinical research papers are to get promoted, to get research grants and to make known, one's findings in order to improve patients' care. Writing papers is also a means of delivering continuous education, therefore publication is essential for any one pursuing an academic career. Research papers can be in the form of case reports, retrospective studies, prospective studies and laboratory or animal research. Two popular formats of writing papers are: the vancouver style and the harvard : 19864742 free full textsharelinkout - more resourcesfull text sourcesmedknow publications and media pvt ltdpubmed commons home. Issue : 2  |  page : g a clinical research e gbolagunte ment of surgery, college of medicine & asir central hospital, king khalid university (formerly king saud university) - abha and asir central hospital, abha, saudi here for correspondence address and of of ct a well-known unwritten law in institutions of higher learning is that of "publish or perish". Two popular formats of writing papers are: the vancouver style and the harvard to cite this article:ajao og. Review article on "writing a clinical research paper" is justified for three reasons: firstly, to renew our knowledge of the subject, to correct a previously unknown unintentional errors in writing clinical research papers and to serve as guidelines for young researchers intending to write scientific institutions of higher learning there is some justification for the phrase unwritten 'law',: "publish or perish", bearing in mind that the duties of a university teacher, in order of priority, are teaching, research and service [1] . Some think research comes before teaching, but there is a consensus that service comes last, except for emergencies. Also academic scientists need to publish in peer-reviewed journals to get research grants, to get promoted and to increase their knowledge. Scientific misconduct is commonly seen as a case of falsification of data, however failure to publish an adequate account of a well-designed clinical trial for example is also a form of scientific misconduct because what can improve patients' care and treatment [2] is being deliberately suppressed. It is just a question of preference and personal paper attempts to recount certain aspects of writing a clinical research paper. Types of research paper clinical research papers can be grouped arbitrarily into four major categories: case reports, retrospective studies, prospective studies and laboratory or animal reports, do not necessarily have to be low-keyed papers.

However, if there are no case reports we probably would not have known about crohn's disease or hirschprung's disease pective studies are relatively common in clinical practice, especially among young consultants, who are just starting their academic life. One major drawback of retrospective studies is that proper randomization is usually not possible and the degree of accuracy of such studies depends on the medical records department and how meticulous the clinical data were documented by the treating ctive studies tend to have more validity than the retrospective because the short comings of the latter are largely eliminated. It is advisable to gather more data than needed, than to find out during the writeup of the paper that some necessary data were not included initially. The clinical trials can involve a group of patients randomly selected, or using the same patients as their own controls. For example, in a clinical trial on methylprednisolone sodium succinate (solu-medrol) in the treatment of typhoid perforation, envelopes labelled "yes" for the steroids usage and "no" for without-steroids can be sealed [7] . Of course, this type of study requires approval by the ethical committee of the institution or hospital, which is responsible for preventing unethical practice in clinical research. There is no doubt that majority of laboratory and animal studies produced break-throughs in clinical medicine. Other sources such as oxford database of perinatal trials and "current contents" : clinical medicine should be sought. Study design in medical research there are certain terminologies that any medical researcher should be familiar with. In all these the studies could be laboratory experiments, epidemiologic studies or controlled clinical trials. For example, a paper on "chest trauma" will be more appropriat for a journal of "thoracic and cardiovascular system" or a journal of "trauma" than a journal of general surgery. In the initial submission of a paper, journal prestige, readership composition and relevance to the topic should all be born in mind [11],[12] . Format of manuscript with the exception of case reports and review articles, most papers have the simrdc structure [11] , that is summary, introduction, materials and methods, result, discussion and conclusion. In the body of the paper, references are indicated by numbers and references listed numerically in the order in which they are cited in the text.

Causes of paper rejection there are many reasons for rejection of a manuscript sent for publication. Usually when a reviewer detects such errors, the credibility of the whole paper is immediately called into question. 3) failure of adherence to the accepted structure of writing a research paper also mitigates against acceptance. It is not the duty of a reviewer or editor to teach the author(s) how to write a research paper. 4) typographical and grammatical errors may not lead to outright rejection of a scientific paper, but they don't enhance its acceptance either. This is one indication that the reference in question was not read, but only copied from another journals require an "abstract" to go along with the paper. This is usually a summary of the key points in the paper and usually contains no more than 250 words. How to deal with a rejected paper when a paper is rejected, in some cases, reasons for the rejection are given. In this situation, it may not be too difficult to rectify the flaws and re-write the paper. When it is outright rejection, it is better to send the revised paper to a different journal. However, in cases of "provisional acceptance subject to certain changes", the revised paper should be sent to the same journal. When a paper is rejected without any reason, it is better for the author to put the paper away for a couple of weeks. When the author goes over the paper again, certain flaws in the paper which were not obvious initially tend to become obvious. Erdos' paper on angiotesin i - converting enzyme was initially rejected before it was finally published in 1975 [3],[20] .

It is now known that this paper has given enormous contribution to our understanding of parkinson's disease. Hans krebs paper on what is now known as the krebs (or tricarboxylic acid) cycle for which he has been awarded the nobel prize, in 1953, was initially rejected by a top journal before being published by the dutch enzymologia [3]. And time consuming research projects are of no use to the scientific community if no one knows about their results. Therefore, the publication of their results should be given as much effort as the research work itself. To those whose papers "place the author at the mercy of malignant jealousy of anonymous rival" [3],[22] , i would like to quote leland clark 13 ' 22) who invented platinum electrode for the oximeter: "young people, and young at heart, take heed. Centerjob uing educationeducation ship360 cemtm centralimplementing mtm in your ing the value of zation centerapha immunization stration ndingfrequently asked in practice340b/safety net t outreach c care tment based ting research involvedparticipatehouse of practitioner meeting & federal pharmacy aphamember your corporate your apha communitieswhy join engage? Pharmacists al research paper al research paper award, offered annually, is intended to promote and encourage high quality clinical research or practice based research in the clinical sciences by recognizing an original research article in this area which has been published in the journal of the american pharmacists association (japha). The paper must represent original research and have been published in japha within two calendar years prior to the screening screening committee will evaluate papers based upon the following criteria (not in rank order):• potential of the paper to translate clinical science or practice based investigations into practice. Quality of the science (quality factors may include but are not limited to: adequate sample size, use of control groups, statistical analysis, research is not purely descriptive, research includes an evaluation component etc). The research should describe a rigorous evaluation of a well designed patient care intervention or practice based initiative. The research is original and innovative while being founded in existing literature and/or theory. The research has had or is likely to have a significant impact on practice, the profession or medication tion/screening association with the editor of japha, a screening committee comprised of members of the clinical sciences section of the apha academy of pharmaceutical research and science will screen all eligible papers published in japha in the previous two years and select and submit three (3) finalists to the apha-aprs awards committee by the screening deadline (september 15). Selection of the recipient is made by the apha-aprs awards nature of the award presented at the apha annual meeting will consist of an engraved plaque for each author of the selected paper. Whittaker, christian hyer, deb lamarche, patricia carroll, and libbey center ship360 tment based ting research an pharmacists op apha y and author resources.

Pharmacists centerjob uing educationeducation ship360 centralimplementing mtm in your ing the value of zation centerapha immunization stration ndingfrequently asked in practice340b/safety net t outreach c care tment based ting research y and author we areapha historic ance and department pharmacy professiongetting the most from your t pharmacistcurrent issue.