This entry was posted by Dave Higgins on Thursday, August 10th, 2006, at 12:01 pm, and was filed in All posts, Miscellaneous. A critically important aspect of any study is determining the appropriate sample size to answer the research question. Studies should be designed to include a sufficient number of participants to adequately address the research question. The formulas presented here generate estimates of the necessary sample size(s) required based on statistical criteria. Provide examples demonstrating how the margin of error, effect size and variability of the outcome affect sample size computations.

In practice we use the sample standard deviation to estimate the population standard deviation. In planning studies, we want to determine the sample size needed to ensure that the margin of error is sufficiently small to be informative.

This formula generates the sample size, n, required to ensure that the margin of error, E, does not exceed a specified value.

E is the margin of error that the investigator specifies as important from a clinical or practical standpoint. Example 1: An investigator wants to estimate the mean systolic blood pressure in children with congenital heart disease who are between the ages of 3 and 5.

In order to ensure that the 95% confidence interval estimate of the mean systolic blood pressure in children between the ages of 3 and 5 with congenital heart disease is within 5 units of the true mean, a sample of size 62 is needed. An investigator wants to estimate the mean birth weight of infants born full term (approximately 40 weeks gestation) to mothers who are 19 years of age and under.

In order to ensure that the 95% confidence interval estimate of the proportion of freshmen who smoke is within 5% of the true proportion, a sample of size 385 is needed.

Suppose that a similar study was conducted 2 years ago and found that the prevalence of smoking was 27% among freshmen. Example 3: An investigator wants to estimate the prevalence of breast cancer among women who are between 40 and 45 years of age living in Boston. A sample of size n=16,448 will ensure that a 95% confidence interval estimate of the prevalence of breast cancer is within 0.10 (or to within 10 women per 10,000) of its true value. Thus, with n=5,000 women, a 95% confidence interval would be expected to have a margin of error of 0.0018 (or 18 per 10,000).

If data are available on variability of the outcome in each comparison group, then Sp can be computed and used in the sample size formula. Note that the formula for the sample size generates sample size estimates for samples of equal size. A major issue is determining the variability in the outcome of interest (σ), here the standard deviation of HDL cholesterol. Samples of size n1=250 and n2=250 will ensure that the 95% confidence interval for the difference in mean HDL levels will have a margin of error of no more than 3 units. Again the issue is determining the variability in the outcome of interest (σ), here the standard deviation in pounds lost over 8 weeks.

Samples of size n1=56 and n2=56 will ensure that the 95% confidence interval for the difference in weight lost between diets will have a margin of error of no more than 3 pounds.

Example 6: An investigator wants to estimate the impact of smoking during pregnancy on premature delivery.

Samples of size n1=508 women who smoked during pregnancy and n2=508 women who did not smoke during pregnancy will ensure that the 95% confidence interval for the difference in proportions who deliver prematurely will have a margin of error of no more than 4%. In the module on hypothesis testing for means and proportions, we introduced techniques for means, proportions, differences in means, and differences in proportions. Here we present formulas to determine the sample size required to ensure that a test has high power.

In designing studies most people consider power of 80% or 90% (just as we generally use 95% as the confidence level for confidence interval estimates). The effect size represents the meaningful difference in the population mean - here 95 versus 100, or 0.51 standard deviation units different. In the planned study, participants will be asked to fast overnight and to provide a blood sample for analysis of glucose levels.

We now substitute the effect size and the appropriate Z values for the selected α and power to compute the sample size.

If data are available on variability of the outcome in each comparison group, then Sp can be computed and used to generate the sample sizes. Example 9: An investigator is planning a clinical trial to evaluate the efficacy of a new drug designed to reduce systolic blood pressure. In order to compute the effect size, an estimate of the variability in systolic blood pressures is needed.

Samples of size n1=232 and n2= 232 will ensure that the test of hypothesis will have 80% power to detect a 5 unit difference in mean systolic blood pressures in patients receiving the new drug as compared to patients receiving the placebo.

The investigator must enroll 258 participants to be randomly assigned to receive either the new drug or placebo. An investigator is planning a study to assess the association between alcohol consumption and grade point average among college seniors.

An investigator wants to evaluate the efficacy of an acupuncture treatment for reducing pain in patients with chronic migraine headaches. Then substitute the effect size and the appropriate Z values for the selected α and power to compute the sample size. Samples of size n1=324 and n2=324 will ensure that the test of hypothesis will have 80% power to detect a 30% difference in the proportions of students who develop flu between those who do and do not use the athletic facilities regularly.

Determining the appropriate design of a study is more important than the statistical analysis; a poorly designed study can never be salvaged, whereas a poorly analyzed study can be re-analyzed. Ramachandran V, Sullivan LM, Wilson PW, Sempos CT, Sundstrom J, Kannel WB, Levy D, D'Agostino RB.

Objective To determine the effects of the structure of contribution disclosure forms on the number of authors not meeting criteria of the International Committee of Medical Journal Editors (ICMJE) and to analyze authors’ contributions for the same article declared first by the corresponding author and then by individual authors. Conclusions The structure of contribution disclosure forms significantly influences the number of contributions reported by authors and their compliance with ICMJE authorship criteria. Conclusions Based on this 1000-article sample, the reported use of medical writing assistance appears low (6%).

Objective To characterize the methodological and statistical advice provided by the instructions for authors of major medical journals.

Design Using citation impact factors for 2001, we identified the top 5 journals from each of 33 medical specialties and the top 15 from general and internal medicine that publish original clinical research.

Results Fewer than half the journals provided any information on statistical methods (TABLE 1).

Conclusions Journal instructions for authors provide little guidance regarding methodological and statistical issues and the advice provided may be unhelpful and at times contradictory. Objective To describe the availability of questionnaires used for research published in 3 high-circulation medical journals. Conclusions Our study shows that 6% of novel questionnaires were published, and only 54% of unpublished questionnaires could be obtained via the corresponding author. Objective We undertook this investigation to characterize the conflict of interest (COI) policies of biomedical journals with respect to authors, peer-reviewers, and editors and to ascertain what information about COI disclosures is publicly available.

Design We performed a cross-sectional survey of a convenience sample of 135 peer-reviewed biomedical journal editors. Conclusions While most journals in our sample report having an author COI policy, the disclosures are not collected or published universally. Objective To assess the added value of peer review by identifying and characterizing editorial changes made to initial submissions of manuscripts that were accepted and published. Design A prospective cohort of original research articles (n = 1107) submitted to the Annals of Internal Medicine, BMJ, and Lancet between January 2003 and April 2003. Conclusions The editorial process makes a wide variety of contributions to improve the clarity, accuracy, and reporting of results. Objective Many journals give authors the opportunity to suggest reviewers to review their paper.

Design Original research papers sent for external review at 10 participating journals between April 1, 2003, and December 31, 2003, in which the author had suggested at least 1 reviewer were included.

Conclusions Author and editor suggested reviewers of biomedical research in a range of specialties did not differ in the quality of their reviews, but ASRs tended to make more favorable recommendations for publication. Design The Journal of Investigative Dermatology is ranked first in impact factor in its clinical and basic science specialty.

Results Forty percent of submitters neither suggested nor excluded reviewers; 39% suggested only, 16% both suggested and excluded, and 5% excluded only. Conclusions Authors excluding reviewers had higher acceptance rates by univariate analysis and multivariate analysis. Objective To determine whether blind peer review, a common method for minimizing reviewer bias, affects acceptance of abstracts to scientific meetings when examined by characteristics of the authors’ institutions.

Design We used American Heart Association (AHA) data, which used open peer review from 2000 to 2001 and blind peer review from 2002 to 2004 for abstracts submitted to its annual Scientific Sessions. Conclusions Our results suggest there is bias in the open peer review process, favoring prestigious institutions within the United States. Objective There is a persistent degree of uncertainty and dissatisfaction with the peer review process around the awarding of grants, underlining the need to validate current procedures. Design Two consecutive years of a pilot project competition at a major university medical center provided the material for a series of experiments. Conclusions The lack of concordance among reviewers on the relative merits of individual research grants indicates that under the classical, small number-reviewer process, there is a risk that funding outcome will depend on who is assigned as reviewers rather than the merits of the project.

Objective Clinical journals serve many lines of communication, including scientist-to-scientist, clinician-to-scientist, scientist-to-clinician, and clinician-to-clinician. Design We developed an online clinical peer review system to identify articles of highest interest for each of a broad range of clinical disciplines. Results To date, MORE has 2015 clinical raters, with 34 974 ratings collected for 6573 articles. Conclusions A peer review system to suit the information interests of specific groups is clearly feasible. Objective While considerable attention has been directed to cases of scientific misconduct in the scientific literature, far less is known about the number and nature of unintentional research errors.

Design All retractions of publications indexed in MEDLINE between 1982 and 2002 were extracted and categorized by 2 reviewers as representing misconduct (fabrication, falsification, or plagiarism), unintentional error (mistakes in sampling or data analysis, failure to reproduce findings, or omission of information), or other causes.

Results Of a total of 395 articles retracted during the study period, only 107 (27.1%) reflected scientific misconduct. Conclusions The findings suggest that unintentional mistakes are a substantially more common cause of retractions in the biomedical literature than scientific misconduct. Objective To determine the extent to which authors cite articles identified in official reports as affected by scientific misconduct, and to characterize the nature of such citations. Design We identified 102 articles from either the National Institutes of Health (NIH) Guide for Grants and Contracts, Findings of Scientific Misconduct, or the US Office of Research Integrity annual reports between 1993 and 2001 as needing retraction or correction, and determined the type of corrigenda posted in PubMed.

Results Of the 102 articles flawed by misconduct, 4 were not indexed in PubMed; 47 were tagged in PubMed with a retraction notice, 26 with an erratum, and 12 with a comment correction. Conclusions Although most articles named in misconduct investigations have an identifiable corrigenda, few citing articles reference the corrigenda in their bibliography. Objective To describe the nature and main concerns of all cases discussed at the Committee of Publication Ethics (COPE) from its inception in April 1997 to September 2004.

Design Observational study reporting number of all cases and breakdown of main problems discussed by COPE. Conclusions Editors are confronted with a wide spectrum of suspected research and publication misconduct before and after publication and have a duty to pursue such cases. Are Authors' Financial Ties With Pharmaceutical Companies Associated With Positive Results or Conclusions in Meta-analyses on Antihypertensive Medications? Objective To determine whether authors’ financial ties with pharmaceutical companies are associated with positive results or conclusions in meta-analyses on antihypertensive medications.

Design Meta-analyses published January 1966 to June 2002 that evaluated antihypertensive medications in nonpregnant adults were included. Conclusions Preliminary data suggest that meta-analyses with and without disclosed financial ties to the pharmaceutical industry are similar in direction of results and quality.

Results One hundred seventy-five of 1596 Cochrane Reviews had a meta-analysis that compared 2 drugs.

Objective Cost-effectiveness analysis can inform policy makers about the efficient allocation of resources.

Design We reviewed published English-language cost-effectiveness analyses cited in MEDLINE between 1976 and 2001.

Conclusions The majority of published cost-effectiveness analyses report highly favorable incremental cost-effectiveness ratios. Objective To identify characteristics of submitted manuscripts that are associated with acceptance for publication at major biomedical journals. Design Prospective cohort of original research articles (n = 1107) submitted for publication January 2003-April 2003 at 3 leading biomedical journals. Conclusions We found no evidence of editorial bias favoring studies with statistically significant results.

Objective To identify new features of publication bias (ie, favorable factors associated with decision to publish) in editorial decision making. Design Cross-sectional, qualitative analysis of discussions at manuscript meetings of JAMA. Results From the list of phrases, we sorted terms such as author characteristics (eg, highly regarded), the manuscript (eg, well-written), and the topic, as well as peer reviewer opinion and scientific aspects of the work (eg, sample size).

Conclusions Studies of editorial publication decision making should assess the relative impact of factors related to scientific merit, journalistic goals, and writing, in addition to statistical significance of results. Objective To evaluate the association between statistically significant results for the primary outcome and the journal impact factor of published clinical trials. Design An existing data set from a retrospective follow-up study (1988-1989) of 3 cohorts of initiated studies evaluating publication bias was used for this analysis.

Results Journal impact factors in our cohorts of trials ranged from 0 to 21.148 (published in 1967-1989).

Conclusions Trials with statistically significant results were more likely to be published in a high-impact journal. Design Analysis of total article submission, submission of articles from countries other than Brazil, and acceptance data from 2000 through 2004.

Results There was a significant trend toward linear increase in the number of submissions along the study period (P = .009).

Conclusions These results suggest that SciELO and MEDLINE indexing contributed to increased manuscript submission to Jornal de Pediatria. Objective Articles published in print journals with limited circulation are cited less frequently than those printed in journals with larger circulations.

Results Of the 553 articles published between 1990 through 1999, 327 articles received 893 citations between 1990 and 2004 (TABLE 6).

Conclusions Open access was associated with an increase in the number of citations received by the articles. Design Retrospective analysis of impact factor data from Institute for Scientific Information (ISI) Journal Citation Reports, Science Edition, 1994 to 2004, and interviews with the 10 editors-in-chief of these journals (except Med J Aust) who had served between 1999 and 2004, conducted from November 2004 to February 2005.

Objective To examine Internet address and uniform resource locator (URL) citation characteristics in medical subspecialty literature using dermatology journals as a case study. Design An automated computer program systematically extracted and analyzed Internet addresses cited in the 3 dermatology journals rated highest for scientific impact: Journal of Investigative Dermatology, Archives of Dermatology, and Journal of the American Academy of Dermatology, published between January 1999 and September 2004.

Results Overall, 7337 journal articles contained 1113 URL citations, of which 18% were inaccessible. Conclusions Internet citations increasingly used and lost in dermatology journals likely reflect URL use and loss across all medical subspecialty literature.

Objective To examine whether reviewers’ assessments of manuscripts are influenced by citations to their own work. Design The International Journal of Epidemiology receives about 700 manuscripts each year, of which about 30% are sent out to reviewers. Conclusions There may be truth in the old professor’s adage that you should cite the work of likely reviewers in your papers.

Objective Scientific meeting presentations garner new media attention, despite the fact that the underlying research is often preliminary and has undergone limited peer review. Conclusions News stories about scientific meeting research presentations often omit basic study facts and caveats.

Objective This research examines the quality of health-related reporting published in the top 100 US consumer magazines, using a validated index of the quality of written consumer health information.

Design The authors purchased and reviewed consumer publications published in August 2003 and likely to include health-related information from the Audit Bureau of Circulations top 100 magazine rankings based on average paid circulation figures. Results Thirty-two magazines, with a combined number of more than 100 million subscribers, met the inclusion criteria and 57 articles were deemed eligible for review. Conclusions Health articles as found in top consumer magazines fail to meet basic quality criteria and could mislead the public. Objective To assess the need for a better reporting standard (such as a mini-CONSORT) for trials reported in abstracts.

Design A total of 209 randomized trials were identified from the proceeding of the American Society of Clinical Oncology conference in 1992. Results Some aspects of trials were well-reported in the conference abstract and full publication abstract: 92% (n = 33) of study Objectives, 94% (n = 34) of participant eligibility, 100% (n = 36) of trial interventions, and 89% (n = 32) of primary outcomes were the same in both abstracts (TABLE 9).

Conclusions Previous research has shown that trials presented as conference abstracts are poorly reported. Results The first result in the abstract was reported to be statistically significant in 70% of randomized controlled trials, 84% of cohort studies, and 84% of case-control studies (TABLE 10). Conclusions Significant results in abstracts are exceedingly common but are often misleading because of erroneous calculations and probably also repetitive trawling of the data. Objective To determine the rate at which abstracts describing results of randomized or controlled clinical trials are subsequently published in full and to investigate study factors associated with full publication. Design Systematic review, searching MEDLINE, Embase, and the Cochrane Library from the start of each database until May 2005 for reports of bibliographic follow-up studies examining the subsequent full publication of randomized or controlled clinical trial results initially presented in abstract or summary form. Results In 23 reports (published 1990-2004) there were follow-up data of 3946 controlled clinical trial abstracts from a wide range of biomedical disciplines. Conclusions Results from almost half of all randomized and controlled clinical trials initially presented at biomedical meetings were not made accessible to researchers through full publication. Objective Although crossover trials enjoy wide use, standards for analysis and reporting have not been established. Design We searched MEDLINE for December 2000 and identified all randomized crossover trials. Results We identified 526 randomized controlled trials, of which 116 were crossover trials.

Conclusions Reports of crossover trials frequently omit important methodological issues in design, analysis, and presentation. Catherine Jane Walter,1 Walter Jo Dumville,2 Catherine Hewitt,2 David Torgerson,2 Philip Drew,1 and John R.

Objective Surgical randomized controlled trials (RCTs) have previously been criticized for using weak methodology. Design All surgical RCTs published in the BMJ, JAMA, Lancet, and New England Journal of Medicine from 1998 to 2004 were identified.

The standard error of the mean is is the value we would expect if we took several samples, and computed all their means, and then took the standard deviation of those means. Eighty percent (80%) of the respondents agreed with the statement that social secirity benefits should not be taxed and 20% said they should be taxed. The larger your sample, the more likely the sample represents the population as a whole, and the more confident you can be about the mean. This module will focus on formulas that can be used to estimate the sample size needed to produce a confidence interval estimate with a specified margin of error (precision) or to ensure that a test of hypothesis has a high probability of detecting a meaningful difference in the parameter. Studies that have either an inadequate number of participants or an excessively large number of participants are both wasteful in terms of participant and investigator time, resources to conduct the assessments, analytic efforts and so on. However, in many studies, the sample size is determined by financial or logistical constraints. Note that there is an alternative formula for estimating the mean of a continuous outcome in a single population, and it is used when the sample size is small (n<30).

When we use the sample size formula above (or one of the other formulas that we will present in the sections that follow), we are planning a study to estimate the unknown mean of a particular outcome variable in a population. The mean birth weight of infants born full-term to mothers 20 years of age and older is 3,510 grams with a standard deviation of 385 grams.

How many freshmen should be involved in the study to ensure that a 95% confidence interval estimate of the proportion of freshmen who smoke is within 5% of the true proportion?

If the investigator believes that this is a reasonable estimate of prevalence 2 years later, it can be used to plan the next study. This is a situation where investigators might decide that a sample of this size is not feasible. The investigators must decide if this would be sufficiently precise to answer the research question. If a study is planned where different numbers of patients will be assigned or different numbers of patients will comprise the comparison groups, then alternative formulas can be used. The plan is to enroll participants and to randomly assign them to receive either the new drug or a placebo. Before presenting the formulas to determine the sample sizes required to ensure high power in a test, we will first discuss power from a conceptual point of view.

The figure below shows the distributions of the sample mean under the null and alternative hypotheses. A statistical test is much more likely to reject the null hypothesis in favor of the alternative if the true mean is 98 than if the true mean is 94. The inputs for the sample size formulas include the desired power, the level of significance and the effect size.

A cross-sectional study is planned to assess the mean fasting blood glucose levels in people who drink at least two cups of coffee per day. Based on prior experience, the investigators hypothesize that 10% of the participants will fail to fast or will refuse to follow the study protocol.

How many patients should be studied to ensure that the power of the test is 90% to detect a 5% difference in the proportion with elevated LDL cholesterol? During the manufacturing process, approximately 10% of the stents are deemed to be defective. If a study is planned where different numbers of patients will be assigned or different numbers of patients will comprise the comparison groups, then alternative formulas can be used (see Howell3 for more details).

Analysis of data from the Framingham Heart Study showed that the standard deviation of systolic blood pressure was 19.0. However, the investigators hypothesized a 10% attrition rate (in both groups), and to ensure a total sample size of 232 they need to allow for attrition.

The plan is to categorize students as heavy drinkers or not using 5 or more drinks on a typical drinking day as the criterion for heavy drinking. The formulas are organized by the proposed analysis, a confidence interval estimate or a test of hypothesis. C-reactive protein, the metabolic syndrome and prediction of cardiovascular events in the Framingham Offspring Study.

Relative importance of borderline and elevated levels of coronary heart disease risk factors. Main outcome measure was the number of authors not satisfying ICMJE criteria (honorary authors). Discrepancy between what corresponding authors declare on 2 separate occasions about their own contributions to the same manuscript indicate that recall bias may be one of the confounding factors of responsible authorship practices.

Good Publication Practice Guidelines for pharmaceutical companies encourage authors to acknowledge medical writing assistance. The sample comprised 100 consecutive articles published up to January 2005 from each of 10 high-ranking (impact factor–based), international, peer-reviewed medical journals from different therapeutic areas. In the pharmaceutical-sponsored studies subset (n = 102 articles), assistance was declared in 10 articles (10%). The final sample of 166 journals was obtained after examining 232 journals (some journals represent more than 1 specialty). General journals were more likely to refer to reporting guidelines but less likely to include advice about statistical issues. Studies using nonnovel questionnaire instruments (eg, CAGE, Behavioral Risk Factor Surveillance Survey) were excluded. Reforms, such as mandatory publication or deposition in an open access archive, are needed to guarantee access to the fundamentally indispensable component of questionnaire research, the questionnaire.

We included a broad range of North American and European, general and specialty medical journals that publish original, clinical research topics, based on impact factor, and the recommendations of experts in the field. Journals less frequently reported COI policies for peer reviewers and editors, and even less commonly publish those disclosures. Experimental and observational studies, systematic reviews, and qualitative, ethnographic, or nonhuman studies were included. Authors often do not disclose potential conflicts of interest or the role of the funding source in submitted manuscripts. We report a study comparing author-suggested reviewers (ASRs) and editor-suggested reviewers (ESRs) of 10 biomedical journals in a range of specialties to investigate differences in review quality, timeliness, and recommendation for publication. Editors were instructed to make decisions about their choice of reviewers in their usual manner. Review quality and timeliness did not differ significantly between ASRs and ESRs (TABLE 3). A total of 228 consecutive submissions of original articles, representing one third of 2003 annual submissions, were analyzed for the effect of authors’ suggestions concerning reviewers on peer review outcome. During the first year of the competition, 11 reviewers rated 32 applications; during the second year, 15 reviewers rated 23 applications.

Depending on the pairings, the top rated project in each stream would have failed the funding cutoff with a frequency of 9% and 35%, respectively. Prior RANKING appears to be a way of harnessing the collective wisdom and producing some stability in funding decisions across time. Practicing clinicians are recruited to the McMaster Online Rating of Evidence (MORE) system and register according to their clinical discipline. Preliminary findings show that it differentiates between clinical disciplines and stimulates the users of the services it creates to use more evidence-based resources, such as original and systematic review articles. To better understand this issue, we examined the characteristics of retracted articles indexed in MEDLINE, focusing on comparisons between misconduct and mistakes. Our analyses compared the characteristics of the retracted article with the timing of the subsequent notification of retraction between articles that were retracted due to unintentional error and scientific misconduct. Substantial differences exist between these 2 categories in publication characteristics, authorship, and reporting. Ten articles only had a link to the NIH Guide Findings of Scientific Misconduct and 3 articles had no corrigendum whatsoever. Analysis of cases as published in COPE reports and, for 2004, from COPE committee meeting minutes.

The most frequent problem presented was duplicate or redundant publication or submission (58 cases), followed by authorship issues (26 cases), lack of ethics committee approval (25 cases), no or inadequate informed consent (22 cases), falsification or fabrication (19 cases), plagiarism (17 cases), unethical research or clinical malpractice (15 cases), and undeclared conflict of interest (8 cases). COPE provides a forum for discussion and advice among editors and a repository of cases for educational purposes. But those with financial ties have a higher proportion of positive conclusions in favor of the study drug.

Data extraction and quality assessment were performed independently by 2 observers using a validated scale to judge the scientific quality of the reviews and a binary scale to grade conclusions.

We found 24 paper-based meta-analyses that matched the Cochrane Reviews; 8 were industry-sponsored, 9 had unknown support, and 7 had no support or were supported by nonindustry sources.

Incremental cost-effectiveness ratios are used commonly to quantify the value of a diagnostic test or therapy. Awareness of potentially influential factors can enable health journal editors as well as policy makers to better judge cost-effectiveness analyses. Studies of experimental and observational design, systematic reviews, and qualitative, ethnographic, or nonhuman studies were included. Submitted manuscripts with randomized, controlled study design or systematic reviews, analyses using descriptive or qualitative methods, sample sizes of 73 or more, and disclosure of the funding source were more likely to be published. We determined that most discussion could be categorized into 3 broad categories: scientific features, journalistic goals, and writing. Only trials with full publication (defined as an article with ≥3 pages) after study enrollment had been completed, at the time of the follow-up, were included (n = 219). The numbers of journals in each journal impact factor quartile were 45 (first quartile), 35 (second quartile), 26 (third quartile), and 13 (fourth quartile). Since there were no changes in the editorial board or in the methods of manuscript submission during this period, 3 events were considered as having a potential impact on submission rates: launch of the bilingual Web site, indexing in the SciELO, and MEDLINE indexing.

The numbers of manuscripts submitted in stages I through IV were 184, 240, 297, and 482, respectively.

SciELO indexing was associated with an increase in Brazilian submissions, whereas MEDLINE indexing led to an increase in both Brazilian and international submissions.

Open access has been shown to improve citation rates in the fields of physics, mathematics, and astronomy. However, the relative changes in impact factors (averaged over 11 years) ranged from 6% to 172% per year.

This phenomenon was perceived by editors-in-chief to occur for various reasons, sometimes including editorial policy. Corresponding authors of articles with inaccessible URLs were contacted regarding the content and importance of the inaccessible information.

Policy changes are needed to stem the loss of cited Internet information in scientific publications. Reviewers are asked to make a decision using 4 categories (accept as is, minor revision, major revision, and reject).

The median number of reviewers per manuscript was 2.6 (interquartile range [IQR], 2-3) and the median number of citations in manuscripts was 28 (IQR, 22-39). We examined whether media stories report basic study facts and caveats, specifically regarding the preliminary nature of the research. Consequently, the public may be misled about the validity and relevance of the science presented.

Articles were included if they made overt claims about the effect of interventions of any kind on health outcomes. Only 2% of the articles dated the source of information quoted, 7% provided references for each claim made, and 14% gave additional contact information for sources. Publishers of consumer magazines are missing an opportunity to increase the current low levels of functional health literacy of the public, at little or no cost. Full publications were identified for 125 trials by searching The Cochrane Central Register of Controlled Trials and PubMed (median time to publication 27 months; interquartile range, 15-43). However, this study suggests that they may contain as much or more useful information than the abstract of a full publication.

For comparison, random samples of 130 abstracts from cohort studies and 130 abstracts from case-control studies were selected. We identified additional reports through citations (Science Citation Index), and reference lists of included reports, author files, and by verbal communication.

Furthermore, we found evidence for publication bias in the controlled clinical trials that investigators did publish in full. We reviewed methodological aspects and quality of reporting in a representative sample of published crossover trials. We abstracted data independently, in duplicate, on 14 design criteria, 13 analysis criteria, and 14 criteria assessing the data presentation.

Guidelines for the conduct and reporting of crossover trials might improve the conduct and reporting of studies using this important trial design. For each surgical RCT included, a nonsurgical RCT, matched for journal and publication year, was also randomly selected. So a P value, interpreted correctly, can tell us about the strength of evidence against the null hypothesis. This gives me (an undergraduate, BioStats student) enough information to understand the concept and enough explanation to practically apply. An illustration: If we sample the height of a billion people, the standard deviation will still be there (as it would if we measured absolutely everybody), but we would start being very confident about the average height of the human being.

These situations can also be viewed as unethical as participants may have been put at risk as part of a study that was unable to answer an important question. For example, suppose a study is proposed to evaluate a new screening test for Down Syndrome. It involves a value from the t distribution, as opposed to one from the standard normal distribution, to reflect the desired level of confidence. We conduct a study and generate a 95% confidence interval as follows 125 + 40 pounds, or 85 to 165 pounds.

The formula above gives the number of participants needed with complete data to ensure that the margin of error in the confidence interval does not exceed E. The investigator plans on using a 95% confidence interval (so Z=1.96) and wants a margin of error of 5 units. Because the estimates of the standard deviation were derived from studies of children with other cardiac defects, it would be advisable to use the larger standard deviation and plan for a study with 62 children.

How many women 19 years of age and under must be enrolled in the study to ensure that a 95% confidence interval estimate of the mean birth weight of their infants has a margin of error not exceeding 100 grams?

Here we are planning a study to generate a 95% confidence interval for the unknown population proportion, p. Using this estimate of p, what sample size is needed (assuming that again a 95% confidence interval will be used and we want the same level of precision)? Suppose that the investigators thought a sample of size 5,000 would be reasonable from a practical point of view. Note that the above is based on the assumption that the prevalence of breast cancer in Boston is similar to that reported nationally. HDL cholesterol will be measured in each participant after 12 weeks on the assigned treatment. Suppose one such study compared the same diets in adults and involved 100 participants in each diet group.

How many women should be enrolled in the study to ensure that the 95% confidence interval for the difference in proportions has a margin of error of no more than 4%?

The effect size is the difference in the parameter of interest that represents a clinically meaningful difference.

To facilitate interpretation, we will continue this discussion with as opposed to Z. Notice also in this case that there is little overlap in the distributions under the null and alternative hypotheses. The effect size is selected to represent a clinically meaningful or practically important difference in the parameter of interest, as we will illustrate. The formulas shown below produce the number of participants needed with complete data, and we will illustrate how attrition is addressed in planning studies. Similar to the issue we faced when planning studies to estimate confidence intervals, it can sometimes be difficult to estimate the standard deviation. Therefore, a total of 35 participants will be enrolled in the study to ensure that 31 are available for analysis (see below). The manufacturer wants to test whether the proportion of defective stents is more than 10%. Recall from the module on Hypothesis Testing that, when we performed tests of hypothesis comparing the means of two independent groups, we used Sp, the pooled estimate of the common standard deviation, as a measure of variability in the outcome. Systolic blood pressures will be measured in each participant after 12 weeks on the assigned treatment.

Mean grade point averages will be compared between students classified as heavy drinkers versus not using a two independent samples test of means. Each will be asked to rate the severity of the pain they experience with their next migraine before any treatment is administered.

Each student will be asked if they used the athletic facility regularly over the past 6 months and whether or not they had the flu.

The sample size must be large enough to adequately answer the research question, yet not too large so as to involve too many patients when fewer would have sufficed.

Gestational weight gain and pregnancy outcome in terms of gestation at delivery and infant birth weight: a comparison between adolescents under 16 and adult women.

In a separate study, corresponding authors of 201 submitted articles, representing 919 authors, received contribution disclosure forms with 11 possible contribution choices to declare contributions of all authors. Journal editors should be aware of the cognitive aspects of survey methodology when they construct self-reports about behavior, such as contribution disclosure forms. The objectives of this study were to determine the proportion of articles from international, high-ranking, peer-reviewed journals that declared medical writing assistance and to explore the association between pharmaceutical sponsorship and medical writing assistance in terms of time to manuscript acceptance.

The proportion of articles declaring pharmaceutical sponsorship and medical writing assistance, and the time interval between manuscript submission and acceptance were calculated.

For pharmaceutical-sponsored studies, the time to publication may be faster when medical writers are used. We obtained the online instructions for authors for each journal between January and May 2003 and identified all material relating to 15 methodological and statistical topics. For inclusion, 2 investigators independently judged that the results of a questionnaire constituted the main outcome of the study. The following other responses were provided: no access to the questionnaire (n = 3), questionnaire only given to collaborators (n = 2), referred to questionnaire description in the article (n = 2), change in job status (n = 1), no structured questionnaire used (n = 1), returned a questionnaire unrelated to the paper (n = 1), returned partial questionnaire (n = 1), and correct e-mail or postal address unavailable (n = 1).

We reviewed each journal’s Web page to identify the editors, and each editor in our sample represented a single journal only.

Ten (11%) journals restrict author submissions based on COI (eg, drug company authors’ papers on their products are not accepted). Specific policies to restrict authorship, or peer-review and editing, were uncommonly reported in our sample.

Extreme variability in the editorial process was observed ranging from near-verbatim publication of submitted manuscripts to extensive additions and deletions of data or text and revised statistical analyses with new tables and figures. Odds ratios (ORs) were calculated with STATA version 7 and are presented with the 95% confidence intervals (CIs). The advantage for authors of excluding reviewers requires processes to eliminate bias during peer review. The US institutions were scored for prestige, combining total National Institutes of Health (NIH) awards (0-2 points) and US News Heart & Heart Surgery hospital ranking (0-2 points), and subsequently categorized as more (3-4 points) or less (0-2 points) prestigious. Four of the top 10 projects identified by RANKING had a greater than 50% of not being funded by the CLASSIC ranking. Research staff reviewed more than 110 clinical journals to select each article that meets critical appraisal criteria for diagnosis, treatment, cause, course, and economics of health care problems.

A stratified random sample of 604 was drawn from the population of 5164 citing articles for a content analysis to determine how the affected articles were used by subsequent researchers. Most problem articles were basic science studies (68% in vitro and 7% animal) and 25% were clinical studies. Reports of outcomes suggest that, in many cases, investigations take a long time and a substantial number of cases cannot be adequately resolved. Meta-analyses were identified by electronically searching PubMed and the Cochrane Database and by hand-searching the reference lists of identified meta-analyses. We found no difference between meta-analyses with or without financial ties in the proportion of positive results. We studied whether Cochrane Reviews and industry-sponsored meta-analyses of the same drugs differed in methodological quality and conclusions.

We investigated whether published studies tend to report favorable cost-effectiveness ratios (less than $20 000, $50 000, and $100 000 per quality-adjusted life year [QALY] gained) and evaluated study characteristics associated with this phenomenon. We revised our classification system iteratively, using internal discussion and peer input until we established 27 subgroups. Results for primary outcomes and publication history of the trials were based on investigator interviews. Citations for the articles published between 1990 through 1999 during these 2 periods were compared using the unpaired t test or Mann-Whitney test. For every volume studied (1990 through 1999), the maximum number of citations per year was received after 2001.

For smaller biomedical journals, open access could be one of the means for improving visibility and thus citation rates. The impact factor is calculated yearly by dividing the number of citations that year to any article published by that journal in the previous 2 years (the numerator) by the number of eligible articles published by that journal in the previous 2 years (the denominator). However, all considered the impact factor a mixed blessing—attractive to researchers but not the best measure of clinical impact. We examined whether the reviewers’ decision was influenced by the number of citations to their work or other manuscript characteristics by abstracting data using a standardized proforma.

The final analysis, which will be based on a larger number of manuscripts and reviewer reports, will provide more robust evidence.

Among the 124 stories covering studies other than randomized trials, 85% failed to mention (explicitly mention or imply) any relevant study limitation (eg, imprecision of small studies, no comparison group in case series, confounding in observational studies).

Most articles failed to acknowledge uncertainty about the participant interventions (74%), risks associated with the interventions (74%), or other possible treatment choices (56%). There is an opportunity for peer-reviewed biomedical publications to provide support to, and help define standards for, the lay press, thereby protecting the public. A sample of 40 trials was selected within a specific area of cancer; 4 trials were later excluded. Likewise, 69% (n = 25) of conference abstracts and 44% (n = 16) of full publication abstracts reported number of participants analyzed, and these numbers were the same only 11% (n = 4) of the time. The quality of reporting of trials in abstracts, both in the proceedings of scientific meetings and in journals, needs to be improved because this may be the only accessible information to which someone appraising a trial has access. I noted the P value for the first relative risk or odds ratio that was mentioned, or calculated it if it was not reported. We excluded reports with less than 2 years of follow-up after the meeting or without information on numbers of abstracts examined or followed. For systematic reviews on efficacy and harm of treatment, authors cannot rely solely on results from fully published controlled clinical trials. So for example, if you specify a mean value of a random sample of a population, a 95% CI of the mean indicates how confident we can be that the true population mean lies within the calculated confidence interval. These data are communicated by a CI, and are important in determining the clinical significance of effects which we observe which we have decided are likely to be real ones.

Studies that are much larger than they need to be to answer the research questions are also wasteful. In sample size computations, investigators often use a value for the standard deviation from a previous study or a study done in a different, but comparable, population.

We will illustrate how attrition is addressed in planning studies through examples in the following sections. The standard deviation of systolic blood pressure is unknown, but the investigators conduct a literature search and find that the standard deviation of systolic blood pressures in children with other cardiac defects is between 15 and 20. The equation to determine the sample size for determining p seems to require knowledge of p, but this is obviously this is a circular argument, because if we knew the proportion of successes in the population, then a study would not be necessary! The standard deviation of the outcome variable measured in patients assigned to the placebo, control or unexposed group can be used to plan a future trial, as illustrated below. In order to ensure that the total sample size of 500 is available at 12 weeks, the investigator needs to recruit more participants to allow for attrition. Each child will then be randomly assigned to either the low fat or the low carbohydrate diet. In order to ensure that the total sample size of 112 is available at 8 weeks, the investigator needs to recruit more participants to allow for attrition. The first is called a Type I error and refers to the situation where we incorrectly reject H0 when in fact it is true.

Similar to the margin of error in confidence interval applications, the effect size is determined based on clinical or practical criteria and not statistical criteria. We compute the sample mean and then must decide whether the sample mean provides evidence to support the alternative hypothesis or not. The figure below shows the same components for the situation where the mean under the alternative hypothesis is 98.

If a sample mean of 97 or higher is observed it is very unlikely that it came from a distribution whose mean is 90. In sample size computations, investigators often use a value for the standard deviation from a previous study or a study performed in a different but comparable population. How many patients should be enrolled in the study to ensure that the power of the test is 80% to detect this difference? If the process produces more than 15% defective stents, then corrective action must be taken.

The standard deviation of the outcome variable measured in patients assigned to the placebo, control or unexposed group can be used to plan a future trial, as illustrated. Based on prior experience with similar trials, the investigator expects that 10% of all participants will be lost to follow up or will drop out of the study.

Pain will be recorded on a scale of 1-100 with higher scores indicative of more severe pain. A test of hypothesis will be conducted to compare the proportion of students who used the athletic facility regularly and got flu with the proportion of students who did not and got flu. The determination of the appropriate sample size involves statistical criteria as well as clinical or practical considerations. Most honorary authors (39.9%) lacked only the third ICMJE criterion (final approval of manuscript). Analysis of variance was used to explore associations between sponsorship, writing assistance, and manuscript acceptance time. Assessments were performed by reading the instructions for authors and validated by text searches for relevant words. For qualifying studies with duplicate corresponding authors, 1 study was randomly selected for inclusion. While 77% report collecting COI information on all author submissions, only 57% publish all author disclosures. Most changes were minor consisting of simple word modifications, statements, and clarifications. Review quality was rated independently using the validated Review Quality Instrument by 2 raters blind to reviewer identity and status. There was no evidence that the effect of reviewer status on review quality, timeliness, and recommendation to accept and recommendation to accept or resubmit varied across journals. Ten reviewers provided optimal consistency for the RANKING method in the first sample but this was not repeated in the second sample. An automated system assigns each qualifying article to 4 clinical raters for each pertinent discipline, and records their online assessments of the article’s relevance and newsworthiness. A total of 132 cases (63%) were relating to papers before publication and 72 (34%) to papers that had already been published; in 8 cases, the question or concern was not related to a particular paper. In contrast, conclusions in meta-analyses with financial ties were positive in 91%, unclear in 4%, neutral in 4%, and negative in none, whereas conclusions in meta-analyses without financial ties were positive in 72%, unclear in 2%, neutral in 17%, and negative in 8%.

Compared with industry-sponsored reviews, more Cochrane Reviews had stated their search methods, had comprehensive search strategies, used more sources to identify studies, made an effort to avoid bias in the selection of studies, reported criteria for assessing the validity of the studies, used appropriate criteria, and described methods of allocation concealment, excluded patients, and excluded studies. Journal impact factor of published trials was assessed using the 1988 Science Citation Index (impact factors of 0 were assigned to journals not in the Science Citation Index). Simple regression was used for trend analysis, 1-way ANOVA was used on rank-transformed data with the Duncan post hoc test to compare the number of submissions in each period, and the Fisher exact test with Finner-Bonferroni P value adjustment was used to compare submissions from countries other than Brazil in the 4 periods. The variation in mean monthly submissions became more pronounced in stages III and IV (TABLE 5). We assessed the influence of open access on citation rates for the Journal of Postgraduate Medicine, a small, multidisciplinary journal that adopted open access without article submission or article access fee.

None of the articles published during 1990 through 1999 received any citation in the year of publication.

In general, the numerator for most journals tended to rise over this period while the denominators tended to drop. The URL inaccessibility was highest in the Journal of Investigative Dermatology (22%) and lowest in Archives of Dermatology (15%) (P = .03). Data were analyzed with logistic regression, accounting for the clustered nature of the data. Among the 61 stories reporting on animal studies, case series, or studies with fewer than 30 people, 67% did not highlight their limited relevance to human health. The first eligible article in each section of each publication was reviewed to ensure consistency. A checklist (based on CONSORT) was used to compare information reported in the 36 conference abstracts with that reported in the corresponding abstract of the subsequent full publications. Additonally, by stating a CI, the P value can be roughly determined even if it is not explicitly stated. If the P value is higher (above our arbitrary threshold of say, 0.05), the evidence against the null hypothesis is poor, and we fail to reject it. To be informative, an investigator might want the margin of error to be no more than 5 or 10 pounds (meaning that the 95% confidence interval would have a width (lower limit to upper limit) of 10 or 20 pounds).

The sample size computation is not an application of statistical inference and therefore it is reasonable to use an appropriate estimate for the standard deviation. Suppose the investigator wants the estimate to be within 10 per 10,000 women with 95% confidence. This is done by computing a test statistic and comparing the test statistic to an appropriate critical value. Therefore, the manufacturer wants the test to have 90% power to detect a difference in proportions of this magnitude. If the new drug shows a 5 unit reduction in mean systolic blood pressure, this would represent a clinically meaningful reduction. How many college seniors should be enrolled in the study to ensure that the power of the test is 80% to detect a 0.25 unit difference in mean grade point averages? Sample size determination involves teamwork; biostatisticians must work closely with clinical investigators to determine the sample size that will address the research question of interest with adequate precision or power to produce results that are clinically meaningful. The survey included questions about the presence of specific policies for authors, peer-reviewers, and editors, any specific restrictions on authors, peer-reviewers, and editors based on COI, and the public availability of these disclosures. Major changes often included toning down the original Conclusions, emphasizing study limitations, or revising statistical analyses. Timeliness was calculated as the interval between dates when reviews were solicited and completed.

There were only 3 statistically significant positive associations among the 105 pairings of the 15 raters, and there were many negative correlations, some quite strongly negative.

Rated articles are transferred to a database that is used to select articles for 3 evidence-based journals and to feed online alerting services: McMaster PLUS and BMJUPDATES+. There were no differences in types of retractions based on the date of publication (before or after 1991) or the type of research (human subjects vs basic research). The problem article was embedded in a string of references in 61% of citing articles; there was specific reference to the problem article in 39%. In the majority of cases (n = 159 [75%]), the committee felt that there were sufficient grounds to pursue cases further. Phrases relating to the journalistic goals (readership needs, timeliness) were nearly as common, followed by phrases related to the writing. We used the journal impact factor of the first full publication after study enrollment was completed for all analyses. In contrast, articles published in 2002, 2003, and 2004 received 3, 7, and 22 citations, respectively, in the year of publication itself. When standardized for the denominator, the average relative changes fell naturally into 2 groups: those that remained constant (ie, increases in crude impact factors were due largely to rises in numerators) and those that did not (ie, increase in crude impact factors were due largely to falls in denominators) (TABLE 7). Archives of Dermatology was the only journal of the 3 examined with a stated Internet referencing policy in the instructions for authors.

TABLE 8 shows the reviewers’ verdicts on manuscripts according to citations to their own work. Articles were evaluated individually by all 3 authors using 7 questions of the DISCERN evaluation tool that address factual information. Lack of information was a major problem in assessing trial quality; 0% of conference abstracts and 3% (n=1) of full publication abstracts reported method of allocation concealment, 11% (n = 4) of conference abstracts and 8% (n = 3) of full publication abstracts reported intention-to-treat analyses. Study factors associated with publication included positive results, higher sample size, industry funding, higher quality of abstract reporting, and multicenter status (TABLE 11).

For example, if your 95% CI does not include zero (or if not zero, the value stated in the null hypothesis), then your P value will be less than 0.05.

The amniocentesis is included as the gold standard and the plan is to compare the results of the screening test to the results of the amniocentesis.

In order to determine the sample size needed, the investigator must specify the desired margin of error. The estimate can be derived from a different study that was reported in the literature; some investigators perform a small pilot study to estimate the standard deviation.

The research team, with input from clinical investigators and biostatisticians, must carefully evaluate the implications of selecting a sample of size n = 5,000, n = 16,448 or any size in between. Because we purposely select a small value for α , we control the probability of committing a Type I error. If the null hypothesis is true (μ=90), then we are likely to select a sample whose mean is close in value to 90. While a better test is one with higher power, it is not advisable to increase α as a means to increase power.

How many patients should be enrolled in the trial to ensure that the power of the test is 80% to detect this difference? On their next migraine (post-treatment), each patient will again be asked to rate the severity of the pain. The investigators feel that a 30% increase in flu among those who used the athletic facility regularly would be clinically meaningful. Disclosure forms filled out twice by corresponding authors for the same manuscript disagreed in 140 cases (69.3%). We contacted the journal editor’s with a minimum of 3 requests, to improve response rate, and provided a written version of the survey for those unable to access the Web site.

Minor changes were classified as additions or deletions of words that improved the clarity, readability, or accuracy of reporting. Disclosure of potential conflicts of interest, any funding source, and its role in the design, conduct, and publication process improved in the final publication.

Recommendation was calculated for 6 journals as proportion recommending acceptance (including minor revision), resubmission, or rejection.

Compared with the CLASSIC method, the RANKING resulted in 18 of 23 projects (78%) changing their rank by more than 3 places; however, disagreement on funding status occurred for only 4 of the projects (17%). Users of these services receive alerts and can search the database according to peer ratings for their own discipline.

Few citing articles (9%) used the problem article as direct support or contrast, 54% used it as indirect support or contrast, and 33% did not address invalid information in the problem article.

Financial ties were defined as author affiliation and funding source, as disclosed in the article. We will perform multiple logistic regression analyses to determine whether other factors are associated with positive conclusions. Reviews with unknown support and reviews with not-for-profit support or no support also had cautious conclusions. Although statistical significance of study findings was rarely explicitly discussed, terms related to the concept of strength and direction of findings were relatively frequent.

If more than 1 article was published in the same year, the best journal impact factor was used. For all years, URL accessibility was significantly associated with top-level domain and directory depth but not associated with the presence of an accession date or a tilde in the URL. Each question was answered in terms of whether the article met or did not meet specific criteria.

The 4 nonsignificant results were all correct, whereas 17 of the 23 significant results (74%) appeared to be wrong (11 of the 17 were easy to verify, because the authors used Fisher exact test, and 6 were highly doubtful). Dichotomous data for study factors were analyzed using relative risk and a random effects model. Only 14% of trials reported a sample size calculation and only 38% of these considered pairing of data in the calculation. Usually, the t look-up tables which are used correspond with two-tailed probability P (when the real value you want to estimate can go in either direction—up or down). Suppose that the collection and processing of the blood sample costs $250 per participant and that the amniocentesis costs $900 per participant. It is important to note that this is not a statistical issue, but a clinical or a practical one. Based on data reported from diet trials in adults, the investigator expects that 20% of all children will not complete the study. The second type of error is called a Type II error and it is defined as the probability we do not reject H0 when it is false.

However, it is also possible to select a sample whose mean is much larger or much smaller than 90. How many students should be enrolled in the study to ensure that the power of the test is 80% to detect this difference in the proportions? In June 2004, corresponding authors of the remaining 82 articles were asked via written correspondence to provide a copy of the questionnaire used in their study.

Major changes were classified as additions or deletions of data, new or revised statistical analyses, or statements affecting the interpretation of results or conclusions.

RE-RANKing during committee discussion resulted in a change of funding status for 2 of the 23 previously ranked projects (<9%). In 16 cases (20%), authors were exonerated, 15 (19%) could not be resolved satisfactorily, and in 23 (29%), the authors’ institution was asked to investigate. The association between journal impact factor and statistical significance of the primary results was examined using the odds ratio. Recalculation was rarely possible for observational studies because the presented results had been adjusted for confounders.

These financial constraints alone might substantially limit the number of women that can be enrolled. For example, suppose we want to estimate the mean birth weight of infants born to mothers who smoke cigarettes during pregnancy. Data from the participants in the pilot study can be used to compute a sample standard deviation, which serves as a good estimate for σ in the sample size formula. Consequently, if there is no information available to approximate p, then p=0.5 can be used to generate the most conservative, or largest, sample size.

A 95% confidence interval will be estimated to quantify the difference in weight lost between the two diets and the investigator would like the margin of error to be no more than 3 pounds. We also documented changes in authorship and disclosure of any funding soure (including its role) or potential conflicts of interest.

The data extraction tool was pretested, and the quality of each meta-analysis was assessed using a validated instrument.

Just as it is important to consider both statistical and clinical significance when interpreting results of a statistical analysis, it is also important to weigh both statistical and logistical issues in determining the sample size for a study. Birth weights in infants clearly have a much more restricted range than weights of female college students.

How many patients should be involved in the study to ensure that the test has 80% power to detect a difference of 10 units on the pain scale? A pilot study demonstrated good reliability between the 3 authors in data extraction and quality assessment. Results from surveying authors regarding inaccessible URL content and importance will be reported. Therefore, we would probably want to generate a confidence interval for the mean birth weight that has a margin of error not exceeding 1 or 2 pounds.

No significant difference (t test) was found in the time-to-first decision for either group. Only 28% (95% CI, 21%-36%) presented CIs or SE so that data could be entered into a meta-analysis. Concerns about the accuracy of ISI counting for the impact factor denominator prompted a few editors to routinely check their impact factor data with ISI.

Just 3% (95% CI, 1%-8%) of trials provided a participant flow diagram and 44% (95% CI, 37%-54%) of trials did not account for all participants in the analysis.

If that is unsuccessful, the infection has been treated by switching to another antibiotic. There have been sporadic reports of successful treatment by infusing feces from healthy donors into the duodenum of patients suffering from C. The efficacy of this approach was tested in a randomized clinical trial reported in the New England Journal of Medicine (Jan. In order to estimate the sample size that would be needed, the investigators assumed that the feces infusion would be successful 90% of the time, and antibiotic therapy would be successful in 60% of cases. How many subjects will be needed in each group to ensure that the power of the study is 80% with a level of significance α = 0.05?

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