Choice Of Study Design Research Articles

Neurophysiological Two-Channel Polysomnographic Device in the Diagnosis of Sleep Apnea

Our objective was to evaluate a portable device (Somté, Compumedics, Australia), which incorporates 2 neurophysiological channels (electroencephalography and electrooculography) with cardiorespiratory monitoring for the diagnosis of obstructive sleep apnea (OSA). Full polysomnography (PSG) and Somté recordings were simultaneously performed in 68 patients with suspected OSA. Data were analyzed blindly by 2 scorers. A good agreement between methods in sleep efficiency was observed (68.8% [18.4] with PSG vs 68% [19.1] with Somté [p: n.s.] for scorer 1, and 67.5% [19.1] vs 68.4% [18.5; p: n.s.] for scorer 2). The apnea-hypopnea index (AHI) obtained with Somté was lower than with PSG: 19 (17.8) vs 21.7 (19) (p < 0.001) for scorer 1, and 16.6 (16.7) vs 20 (18.8) (p < 0.001) for scorer 2. The sensitivity of Somté for a PSG-AHI > 5 was 91% for scorer 1 and 90% for scorer 2, while specificity was 77% and 90%, respectively. The areas under the receiver operating curve for different PSG-AHI cutoff points (≥ 5, ≥ 15, and ≥ 30) were 0.81, 0.90, and 0.86, respectively, for scorer 1, and 0.90, 0.88, and 0.83 for scorer 2. These data suggest that Somté is an effective device to identify sleep and respiratory variables in patients with suspected OSA.

Randomized controlled trials and meta-analysis in medical education: What role do they play?

Education researchers seek to understand what works, for whom, in what circumstances. Unfortunately, educational environments are complex and research itself is highly context dependent. Faced with these challenges, some have argued that qualitative methods should supplant quantitative methods such as randomized controlled trials (RCTs) and meta-analysis. I disagree. Good qualitative and mixed-methods research are complementary to, rather than exclusive of, quantitative methods. The complexity and challenges we face should not beguile us into ignoring methods that provide strong evidence. What, then, is the proper role for RCTs and meta-analysis in medical education? First, the choice of study design depends on the research question. RCTs and meta-analysis are appropriate for many, but not all, study goals. They have compelling strengths but also numerous limitations. Second, strong methods will not compensate for a pointless question. RCTs do not advance the science when they make confounded comparisons, or make comparison with no intervention. Third, clinical medicine now faces many of the same challenges we encounter in education. We can learn much from other fields about how to handle complexity in RCTs. Finally, no single study will definitively answer any research question. We need carefully planned, theory-building, programmatic research, reflecting a variety of paradigms and approaches, as we accumulate evidence to change the art and science of education.

Power Comparison of Summary Measure, Mixed Model, and Survival Analysis Methods for Analysis of Repeated-Measures Trials

In two-group repeated-measures studies, a traditional statistical approach is to base analysis directly on the observed continuous measurements, using either summary measures or a mixed linear model. In some medical studies, however, an alternate approach has been taken: Declare the occurrence of an “event” when the sequence of measurements crosses a prespecified threshold, and compare the groups with respect to time to event using the log-rank test. This approach is appealing to clinicians, but clearly involves a loss of information and therefore statistical efficiency. The aim of this article is to quantify the degree of power loss in the context of the random line model. We also compare the summary measures approach to the random line approach. In regard to the efficiency loss with the survival analysis approach, we find that the loss ranges, depending on the location of the threshold, from moderate to dramatic. Using an optimally weighted log-rank test in place of the standard log-rank test leads to minimal gain in efficiency. In regard to analysis based on the original continuous measurements, for testing the slope a weighted summary measure appears to be the best overall choice, whereas for testing the intercept the maximum likelihood (ML) approach is typically much more efficient than the summary measures approach, although the efficiency of the ML approach can be compromised in studies with a small number of observation timepoints. These results have obvious implications for the choice of study design and analysis.

Juvenile Toxicity: Are We Asking the Right Questions?

The recent increase in numbers of juvenile toxicity studies over the past few years has doubtless added to our knowledge of the development of organ systems in the young rodent, but it is perhaps rather more difficult to answer the questions as to whether this body of work has served us well in terms of assessing risk in the pediatric population. If there are shortcomings, are they the result of poor study design or poor sensitivity of the model, or are the wrong questions being posed? This article provides a superficial overview of the progress made thus far and considers which aspects of study design and model choice currently fail to adequately address the major issues surrounding pediatric toxicology.

Prospective Observational Studies to Assess Comparative Effectiveness: The ISPOR Good Research Practices Task Force Report

ObjectiveIn both the United States and Europe there has been an increased interest in using comparative effectiveness research of interventions to inform health policy decisions. Prospective observational studies will undoubtedly be conducted with increased frequency to assess the comparative effectiveness of different treatments, including as a tool for “coverage with evidence development,” “risk-sharing contracting,” or key element in a “learning health-care system.” The principle alternatives for comparative effectiveness research include retrospective observational studies, prospective observational studies, randomized clinical trials, and naturalistic (“pragmatic”) randomized clinical trials. MethodsThis report details the recommendations of a Good Research Practice Task Force on Prospective Observational Studies for comparative effectiveness research. Key issues discussed include how to decide when to do a prospective observational study in light of its advantages and disadvantages with respect to alternatives, and the report summarizes the challenges and approaches to the appropriate design, analysis, and execution of prospective observational studies to make them most valuable and relevant to health-care decision makers. RecommendationsThe task force emphasizes the need for precision and clarity in specifying the key policy questions to be addressed and that studies should be designed with a goal of drawing causal inferences whenever possible. If a study is being performed to support a policy decision, then it should be designed as hypothesis testing—this requires drafting a protocol as if subjects were to be randomized and that investigators clearly state the purpose or main hypotheses, define the treatment groups and outcomes, identify all measured and unmeasured confounders, and specify the primary analyses and required sample size. Separate from analytic and statistical approaches, study design choices may strengthen the ability to address potential biases and confounding in prospective observational studies. The use of inception cohorts, new user designs, multiple comparator groups, matching designs, and assessment of outcomes thought not to be impacted by the therapies being compared are several strategies that should be given strong consideration recognizing that there may be feasibility constraints. The reasoning behind all study design and analytic choices should be transparent and explained in study protocol. Execution of prospective observational studies is as important as their design and analysis in ensuring that results are valuable and relevant, especially capturing the target population of interest, having reasonably complete and nondifferential follow-up. Similar to the concept of the importance of declaring a prespecified hypothesis, we believe that the credibility of many prospective observational studies would be enhanced by their registration on appropriate publicly accessible sites (e.g., clinicaltrials.gov and encepp.eu) in advance of their execution.

Analytic choices in road safety evaluation: Exploring second-best approaches

Conducting rigorous before-and-after studies is essential for improving knowledge regarding the effects of road safety measures. However, state-of-the-art approaches like the empirical Bayes or fully Bayesian techniques cannot always be applied, as the data required by these approaches may be missing or unreliable. The choice facing researchers in such a situation is to either apply “second-best” approaches or abstain from doing an evaluation study. An objection to applying second-best approaches is that these approaches do not control as well for confounding factors as state-of-the-art approaches. This paper explores the implications of choice of study design by examining how the findings of several evaluation studies made in Norway depend on choices made with respect to:1.Using the empirical Bayes approach versus using simpler approaches;2.Use or non-use of a comparison group;3.The choice of comparison group when there is more than one candidate.It is found that the choices made with respect to these points can greatly influence the estimates of safety effects in before-and-after studies. Two second-best techniques (i.e. techniques other than the empirical Bayes approach) for controlling for confounding factors were tested. The techniques were found not to produce unbiased estimates of effect and their use is therefore discouraged.

Comparing treatments for idiopathic sudden sensorineural hearing loss

Comparing treatments for idiopathic sudden sensorineural hearing loss

Contaminant biomonitoring programs in the Great Lakes region: Review of approaches and critical factors

Since the 1970s, several formal biomonitoring programs have been initiated to monitor temporal and spatial trends of persistent, bioaccumulative, and (or) toxic chemicals (PBTs) in the Great Lakes. Researchers have used a variety of approaches to deal with common issues that arise in these programs and there is considerable debate in the literature as to the most appropriate methods to use. Here, we critically review factors of importance in biomonitoring programs and common methods used for dealing with them under three main categories: organism-specific factors (lipid, age, size, sex, growth and bioenergetics, diet, and chemical biotransformation), study design (choice of tissue type, compositing, replication and length of monitoring program, sampling frequency, selection of contaminants to include in monitoring programs, and use of specimen banks for retrospective studies), and data analysis (accounting for changes in analytical methodology, treat- ment of censored data, assessment of compound classes, comparison of empirical models, mechanistic models, and spatial assessments). We use data from the literature as well as longterm measurements of polychlorinated biphenyls (PCBs) in lake trout (Salvelinus namaycush) collected in Lake Ontario as part of monitoring programs run by Environment Canada, the On- tario Ministry of the Environment, and the United States Environmental Protection Agency to illustrate these factors. We find that, in general, there are several defensible methods, ranging from simple to complex, to deal with the issues consid- ered here, with each having specific advantages and disadvantages. The optimal approach depends largely on the program objectives, particularly if the results are meant for the public (understandable without a scientific background) or for re- search purposes (balance between complexity versus simplicity). Given that data analysis typically requires fewer resources compared to other aspects of monitoring programs, it may be feasible to use more than one data analysis approach to in- crease credibility of the results and to improve comparability of data among studies. The importance of conducting prelimi- nary surveys and (or) pilot studies and regular review of ongoing programs (e.g., through a power analysis) is emphasized.

Opportunities for minimization of confounding in observational research

Observational epidemiological studies are increasingly used in pharmaceutical research to evaluate the safety and effectiveness of medicines. Such studies can complement findings from randomized clinical trials by involving larger and more generalizable patient populations by accruing greater durations of follow-up and by representing what happens more typically in the clinical setting. However, the interpretation of exposure effects in observational studies is almost always complicated by non-random exposure allocation, which can result in confounding and potentially lead to misleading conclusions. Confounding occurs when an extraneous factor, related to both the exposure and the outcome of interest, partly or entirely explains the relationship observed between the study exposure and the outcome. Although randomization can eliminate confounding by distributing all such extraneous factors equally across the levels of a given exposure, methods for dealing with confounding in observational studies include a careful choice of study design and the possible use of advanced analytical methods. The aim of this paper is to introduce some of the approaches that can be used to help minimize the impact of confounding in observational research to the reader working in the pharmaceutical industry.

The Quality of Modern Cross-Sectional Ecologic Studies: A Bibliometric Review

The ecologic study design is routinely used by epidemiologists in spite of its limitations. It is presently unknown how well the challenges of the design are dealt with in epidemiologic research. The purpose of this bibliometric review was to critically evaluate the characteristics, statistical methods, and reporting of results of modern cross-sectional ecologic papers. A search through 6 major epidemiology journals identified all cross-sectional ecologic studies published since January 1, 2000. A total of 125 articles met the inclusion requirements and were assessed via common evaluative criteria. It was found that a considerable number of cross-sectional ecologic studies use unreliable methods or contain statistical oversights; most investigators who adjusted their outcomes for age or sex did so improperly (64%), statistical validity was a potential issue for 20% of regression models, and simple linear regression was the most common analytic approach (31%). Many authors omitted important information when discussing the ecologic nature of their study (31%), the choice of study design (58%), and the susceptibility of their research to the ecological fallacy (49%). These results suggest that there is a need for an international set of guidelines that standardizes reporting on ecologic studies. Additionally, greater attention should be given to the relevant biostatistical literature.

Procalcitonin for Triage of Patients with Respiratory Tract Symptoms: A Case Study in the Trial Design Process for Approval of a New Diagnostic Test for Lower Respiratory Tract Infections

Symptoms of cough, fever, chest pain, and shortness of breath are common reasons that patients seek medical care, and they can be due to a variety of medical conditions, including lower respiratory tract infection (LRTI). Only a small proportion of these patients will actually have a bacterial etiology, but many will receive antibiotic treatment because physicians cannot readily determine the etiology at the time of presentation. Current diagnostic methodologies are not sensitive or specific enough to reliably distinguish bacterial from viral or noninfectious etiologies. Procalcitonin (PCT) is a marker of host response. PCT serum levels are elevated in patients with bacterial infection, compared with levels in those with viral infections or other inflammatory pulmonary conditions. Studies have suggested that the determination of PCT levels can identify a subset of patients with LRTI symptoms who can safely avoid antibiotic treatment. As with any new test, clinical trials are necessary to demonstrate the safety and efficacy of the test to obtain U.S. Food and Drug Administration clearance. However, in the absence of standard reference methods for comparison that are reliably sensitive and specific, meeting the regulatory requirements for proof of safety and efficacy is a major challenge. Additional challenges include the choice of study design, the definition and determination of end points, and the justification of statistical analysis.

Cochrane review: Topical fluoride as a cause of dental fluorosis in children

Cochrane review: Topical fluoride as a cause of dental fluorosis in children

Issues for researchers to consider when using health-related quality of life outcomes in cancer research

Maintaining quality of life for patients with cancer is a key factor when developing services related to diagnosis, treatment, recovery and/or terminal care. This paper questions whether health-related quality of life (HRQoL) is an appropriate measure of quality of life given that it does not assess factors reported by patients as being most influential, e.g. contact with family and social/cultural interaction. Ambiguity related to the definition and understanding of anxiety, depression and distress as outcomes commonly used by clinicians and researchers when measuring HRQoL in cancer research is also addressed by this paper. The findings of many cancer studies are interpreted and presented on very broad and poorly defined concepts thus preventing the development of a coherent and true understanding of how these outcomes influence quality of life for cancer patients. The authors of this paper conclude that the documentation and clear explanation of the concepts underpinning the choice of instrument and study design is essential but also the inclusion of outcomes related to social support and interaction would provide a more accurate account of quality of life issues in cancer research.

Evaluation considerations: measures and methods

There is a pressing need to effectively evaluate safety promotion actions worldwide, to inform the skeptics and funders about the real impact of injuries on societies in hindering their development,...

Eager and delayed contract monitoring for call-by-value and call-by-name evaluation

Contracts are a proven tool in software development. They provide specifications for operations that may be statically verified or dynamically validated by contract monitoring. We investigate the properties of contract monitoring for languages with contracts and effects using a monadic semantics. We study three combinations of evaluation orders and contract monitoring styles: call-by-value and call-by-name with eager monitoring and call-by-name with delayed monitoring. In each case, an effect system ensures that contract monitoring does not change the meaning of a program and guarantees that contract monitoring is idempotent. The monadic semantics enables us to study design choices, to formalize implementations, to pinpoint the differences between contracts in the three combinations, and to verify algebraic laws.

Using a fluoridated supplement with a high fluoride concentration in children aged under 6 years may increase the risk of fluorosis

The Cochrane Oral Health Group's Trials Register, Cochrane Central Register of Controlled Trials, Medline, Embase, BIOSIS, Dissertation Abstracts and LILACS/BBO databases were searched. Also, reference lists from relevant articles and five journals (Community Dentistry and Oral Epidemiology, Caries Research, Journal of Dental Research, British Dental Journal, Journal of Public Health Dentistry) were searched by hand, and experts in the field of preventive dentistry and oral epidemiology contacted. Studies [randomised controlled trials (RCT), quasi-RCT, cohort studies, case-control studies and cross-sectional surveys] were selected if they had included children under the age of 6 years when topical fluorides were administered, and in which fluoride toothpastes, mouthrinses, gels, foams, paint-on solutions and varnishes were compared with an alternative fluoride treatment, placebo or no intervention group. Data from all selected studies were extracted by two review authors. Risk ratios (RR) for controlled, prospective studies and odds ratios (OR) for case-control studies or cross-sectional surveys were extracted or calculated. Where both adjusted and unadjusted risk ratios or OR were presented, the adjusted value was included in the meta-analysis. From 3573 identified papers, 25 studies were included: two RCT, one cohort study, six case-control studies and 16 cross-sectional surveys. Only one RCT was judged to be at low risk of bias. The other RCT and all observational studies were judged to be at moderate to high risk of bias. Studies were included in four intervention/ exposure comparisons. A statistically significant reduction in fluorosis was found if brushing of a child's teeth with fluoride toothpaste commenced after the age of 12 months [OR, 0.70; random-effects 95% confidence interval (CI) for topical fluoride, 0.57-0.88; data from observational studies]. Inconsistent but statistically significant associations were found between occurrence of fluorosis and starting use of fluoride toothpaste/ toothbrushing before or after the age of 24 months (data from observational studies). From the RCT, use of higher concentrations of fluoride was associated with an increased risk of fluorosis. No significant association between the frequency of toothbrushing or the amount of fluoride toothpaste used and fluorosis was found. There should be a balanced consideration of the benefits of topical fluorides in caries prevention and the risk of the development of fluorosis. Most of the available evidence focuses on mild fluorosis. There is weak unreliable evidence that starting the use of fluoride toothpaste in children aged <12 months may be associated with an increased risk of fluorosis. The evidence if use begins between the age of 12 and 24 months is equivocal. If the risk of fluorosis is of concern, the fluoride level of toothpaste for young children (under 6 years of age) is recommended to be lower than 1000 parts per million (ppm). More evidence from studies with low risk of bias is needed. Future trials assessing the effectiveness of different types of topical fluorides (including toothpastes, gels, varnishes and mouthrinses) or different concentrations or both should ensure that they include an adequate followup period in order to collect data on potential fluorosis. As it is unethical to propose RCT to assess fluorosis itself, further observational studies will necessarily be undertaken in this area. Attention does, however, need to be given to the choice of study design, bearing in mind that prospective, controlled studies will be less susceptible to bias than retrospective and/ or uncontrolled studies.

Topical fluoride as a cause of dental fluorosis in children.

For many years, topical use of fluorides has gained greater popularity than systemic use of fluorides. A possible adverse effect associated with the use of topical fluoride is the development of dental fluorosis due to the ingestion of excessive fluoride by young children with developing teeth. To describe the relationship between the use of topical fluorides in young children and the risk of developing dental fluorosis. Electronic search of the Cochrane Oral Health Group Trials Register, CENTRAL, MEDLINE, EMBASE, BIOSIS, Dissertation Abstracts and LILACS/BBO. Reference lists from relevant articles were searched. Date of the most recent searches: 9th March 09. Randomised controlled trials (RCTs), quasi-RCTs, cohort studies, case-control studies and cross-sectional surveys, in which fluoride toothpastes, mouthrinses, gels, foams, paint-on solutions, and varnishes were compared to an alternative fluoride treatment, placebo or no intervention group. Children under the age of 6 years at the time topical fluorides were used. Data from all included studies were extracted by two review authors. Risk ratios for controlled, prospective studies and odds ratios for case-control studies or cross-sectional surveys were extracted or calculated. Where both adjusted and unadjusted risk ratios or odds ratios were presented, the adjusted value was included in the meta-analysis. 25 studies were included: 2 RCTs, 1 cohort study, 6 case-control studies and 16 cross-sectional surveys. Only one RCT was judged to be at low risk of bias. The other RCT and all observational studies were judged to be at moderate to high risk of bias. Studies were included in four intervention/exposure comparisons. A statistically significant reduction in fluorosis was found if brushing of a child's teeth with fluoride toothpaste commenced after the age of 12 months odds ratio 0.70 (random-effects: 95% confidence interval 0.57 to 0.88) (data from observational studies). Inconsistent statistically significant associations were found between starting using fluoride toothpaste/toothbrushing before or after the age of 24 months and fluorosis (data from observational studies). From the RCTs, use of higher level of fluoride was associated with an increased risk of fluorosis. No significant association between the frequency of toothbrushing or the amount of fluoride toothpaste used and fluorosis was found. There should be a balanced consideration between the benefits of topical fluorides in caries prevention and the risk of the development of fluorosis. Most of the available evidence focuses on mild fluorosis. There is weak unreliable evidence that starting the use of fluoride toothpaste in children under 12 months of age may be associated with an increased risk of fluorosis. The evidence for its use between the age of 12 and 24 months is equivocal. If the risk of fluorosis is of concern, the fluoride level of toothpaste for young children (under 6 years of age) is recommended to be lower than 1000 parts per million (ppm).More evidence with low risk of bias is needed. Future trials assessing the effectiveness of different types of topical fluorides (including toothpastes, gels, varnishes and mouthrinses) or different concentrations or both should ensure that they include an adequate follow-up period in order to collect data on potential fluorosis. As it is unethical to propose RCTs to assess fluorosis itself, it is acknowledged that further observational studies will be undertaken in this area. However, attention needs to be given to the choice of study design, bearing in mind that prospective, controlled studies will be less susceptible to bias than retrospective and/or uncontrolled studies.

Error prevention in online forms: Use color instead of asterisks to mark required-fields

In this study, a simple but important user interface design choice is examined: when marking required-fields in online forms, should GUI designers stick with the often used asterisk that many form design guidelines cite as the de-facto web standard, or should they choose a colored background as a new design solution to visually signal which input fields are required? An experiment with 24 participants was conducted to test the hypotheses that efficiency, effectiveness and satisfaction ratings of colored required-fields exceed those of asterisk-marked required-fields. Results indicate that colored required field marking leads to fewer errors, faster form fill-in in and higher user satisfaction.

Assessment of incidence of inhibitors in patients with haemophilia

In patients with haemophilia, the development of neutralizing allo-antibodies ('inhibitors') while receiving the deficient clotting factor is relatively common during the patients' initial treatment. Among treated patients with haemophilia who do not develop inhibitors early on, the later incidence is considerably lower. Therefore, the evaluation of potential risk factors for their tendency to give rise to inhibitors is best performed separately in previously untreated and previously treated patients. We discuss potential implications of study design and analysis choices on the validity of inferences from studies assessing inhibitor incidences.

Primary Care: Too Important to Fail

The principal goals of health care reform are to improve quality, increase access, and contain costs. In this issue, Pham and colleagues calculated that a typical primary care clinician must coordi...