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Differences between systematic reviews and health technology assessments: a trade-off between the ideals of scientific rigor and the realities of policy making.

OBJECTIVES: To elucidate important differences between a health technology assessment (HTA) and a systematic review, using an HTA of positron emission tomography (PET) as an example. METHODS: Interviews with seventeen individuals who were authors or users of the PET HTA. RESULTS: Those interviewed identified seven areas in which HTAs often differ from traditional systematic reviews: (i) methodological standards (HTAs may include literature of relatively poor methodological quality if a topic is of importance to decision-makers), (ii) replication of previous studies (relatively common for HTAs but not systematic reviews), (iii) choice of topics (more policy oriented for HTAs, while systematic reviews tend to be driven by researcher interest), (iv) inclusion of content experts and policy-makers as authors (policy-makers more likely to be included in HTAs, although there are potential conflicts of interest), (v) inclusion of economic evaluations (more often with HTAs, although economic evaluations based upon poor clinical data may not be useful), (vi) making policy recommendations (more likely with HTAs, although this must be done with caution), and (vii) dissemination of the report (more often actively done for HTAs). CONCLUSIONS: This case study of an HTA of PET scanning confirms that HTAs are a bridge between science and policy and require a balance between the ideals of scientific rigor and the realities of policy making.

Cost-Benefit Analysis↗

Errors in NAPL volume estimates due to systematic measurement errors during partitioning tracer tests.

During moment-based analyses of partitioning tracer tests, systematic errors in volume and concentration measurements propagate to yield errors in the saturation and volume estimates for nonaqueous phase liquid (NAPL). Derived expressions could be applied to help practitioners bracket their estimates of NAPL saturation and volume obtained from such tests. In practice, many of these effects may be overshadowed by other complications experienced in the field. Errors are propagated for systematic constant (offset) volume, proportional volume, and constant (offset) concentration errors. Previous efforts to quantify the impact of these errors were predicated upon the specific assumption that nonpartitioning and partitioning masses were equal. The current work relaxes that assumption and is therefore more general in scope. Through the use of nondimensional concentration, systematic proportional concentration errors do not affect the accuracy of the method. Specific consideration needs to be given to accurate flow measurements and minimizing baseline concentration errors when performing partitioning tracer tests in order to prevent the propagation of systematic errors.

Environmental Monitoring↗

Systematic procedure for designing processes with multiple environmental objectives.

Evaluation of multiple objectives is very important in designing environmentally benign processes. It requires a systematic procedure for solving multiobjective decision-making problems due to the complex nature of the problems, the need for complex assessments, and the complicated analysis of multidimensional results. In this paper, a novel systematic procedure is presented for designing processes with multiple environmental objectives. This procedure has four steps: initialization, screening, evaluation, and visualization. The first two steps are used for systematic problem formulation based on mass and energy estimation and order of magnitude analysis. In the third step, an efficient parallel multiobjective steady-state genetic algorithm is applied to design environmentally benign and economically viable processes and to provide more accurate and uniform Pareto optimal solutions. In the last step a new visualization technique for illustrating multiple objectives and their design parameters on the same diagram is developed. Through these integrated steps the decision-maker can easily determine design alternatives with respect to his or her preferences. Most importantly, this technique is independent of the number of objectives and design parameters. As a case study, acetic acid recovery from aqueous waste mixtures is investigated by minimizing eight potential environmental impacts and maximizing total profit. After applying the systematic procedure, the most preferred design alternatives and their design parameters are easily identified.

Algorithms↗

Systematic reviews of diagnostic research. Considerations about assessment and incorporation of methodological quality.

The aim of this paper is to provide a theoretical background for performing and reading systematic reviews of diagnostic studies. We first discuss items for assessment of methodological quality in diagnostic studies and then present methods on how to incorporate these quality measures in systematic reviews. The items of internal validity determine whether the presented results of the individual studies are unbiased and can be trusted. Items of external validity determine to what extent the results are applicable outside the population in which the study was performed. The issues concern the adequacy of the study population, the performance and interpretation of the diagnostic tests and the presentation of the results. Several methods exist for incorporation of issues of methodological quality into systematic reviews, such as subgroup analyses, meta-regression analysis, and methodological scores. Publications of diagnostic studies should provide sufficient information to enable assessment of the methodological quality. Furthermore, publication of results of subgroup analyses should be promoted. Methodological criteria lists might help to improve the quality of systematic reviews of diagnostic research. With the items of methodological quality in mind the general practitioner might be better equipped to critically read and interpret diagnostic reviews.

Epidemiologic Studies↗

Assessing for violence during pregnancy using a systematic approach.

OBJECTIVES: The purpose of this study was to determine whether a systematic, multiple assessment protocol could increase reporting of prenatal violence compared with a one-time routine assessment. METHOD: In 1994, the Maternity Care Coordination (MCC) program in a health department prenatal clinic in North Carolina implemented a concise, systematic assessment protocol on all 384 women who enrolled in the program from April 1994 to April 1995. The protocol assessed for violence at three times during pregnancy using the direct question, "Have you been hit, slapped, kicked, or hurt during this pregnancy?" To determine the effectiveness of the system, we retrospectively examined the 1991-1993 MCC records (n = 1056) in which the care coordinators routinely screened all clients for violence at their first visit only. RESULTS: Compared with the routine assessment approach, the new systematic assessment protocol increased reporting of prenatal violence at the initial prenatal visit from 6.3% to 10.9% (relative risk = 1.7, 95% confidence interval = 1.2, 2.5), and the multiple assessments increased reporting of prenatal violence to 14.1% (relative risk = 2.2, 95% confidence interval = 1.6, 3.1). CONCLUSIONS: Our study suggests that a concise and systematic screening technique using direct questions combined with multiple assessments increased reporting of prenatal violence compared with a single routine assessment.

Confidence Intervals↗

Unsupervised concept learning and value systematicity: a complex whole aids learning the parts.

Ease of learning new concepts may best be understood by simultaneously considering models of learning and theories of how "good" systems of categories are organized. The authors tested the effects on learning of value systematicity, a proposed organizing principle: If 1 attribute is predictive of another, it should predict still more. This principle derives from focused sampling in the internal feedback model (D. Billman & E. Heit, 1988) of unsupervised, or observational, learning. In 3 experiments, the authors tested how the organization of structure in input (value systematicity) affected unsupervised learning of categories about alien animals. Across all experiments, learning a target rule was easier in conditions with high value systematicity, relative to several low systematicity controls. The authors compare results to predictions of several learning models and consider the links between learning and the resulting category structure.

Adult↗

Systematic reviews incorporating evidence from nonrandomized study designs: reasons for caution when estimating health effects.

Systematic reviews that include nonrandomized studies (NRS) face a number of logistical challenges. However, the greatest threat to the validity of such reviews arises from the differing susceptibility of randomized controlled trials (RCTs) and NRS to selection bias. Groups compared in NRS are unlikely to be balanced because of the reasons leading study participants to adopt different health behaviours or to be treated differentially. Researchers can try to minimize the susceptibility of NRS to selection bias both at the design stage, for example, by matching participants on key prognostic factors, and during data analysis, for example, by regression modelling. However, because of logistical difficulties in matching, imperfect knowledge about the relationships between prognostic factors and between prognostic factors and outcome, and measurement limitations, it is inevitable that estimates of effect size derived from NRS will be confounded to some extent. Researchers, reviewers and users of evidence alike need to be aware of the consequences of residual confounding. In poor quality RCTs, selection bias tends to favour the new treatment being evaluated. Selection bias need not necessarily lead to systematic bias in favour of one treatment but, even if it acts in an unpredictable way, it will still give rise to additional, nonstatistical uncertainty bias around the estimate of effect size. Systematic reviews of NRS studies run the risk of compounding these biases. Nutritional choices and uptake of health education about nutrition are very likely to be associated with potential confounding factors. Therefore, pooled estimates of the effects of nutritional exposures and their confidence intervals are likely to be misleading; reviewers need to take into account both systematic and uncertainty bias.

Bias↗

The management of established postherpetic neuralgia: a comparison of the quality and content of traditional vs. systematic reviews.

In the face of an exponential increase in published biomedical studies, dermatologists frequently turn to review articles in order to keep abreast of important developments in the treatment of skin diseases. Traditional review articles have recently been criticized on the basis of their incompleteness and susceptibility to bias. Such biases can be minimized by employing a systematic approach to gathering, combining and interpreting the evidence of treatment efficacy. Using eight predetermined quality criteria, we compared the quality of 10 traditional review with one systematic review of treatments for postherpetic neuralgia, which were identified from the Medline database for 1992-96. None of the 10 traditional review articles satisfied all eight criteria: one satisfied five, two satisfied four and the rest satisfied two or fewer criteria. There was a wide variation in the recommendations of the authors for the treatment of postherpetic neuralgia, often based on anecdotal evidence and clinical experience. On the other hand, the systematic review fulfilled seven of the eight quality criteria, failing only to discuss future directives. Furthermore, treatment recommendations were made solely on the basis of randomized controlled trials, which are considered to be the gold standard for measuring the benefits of any intervention. The variation in quality and treatment recommendations of traditional reviews is worrying. Systematic reviews should be encouraged in dermatology because they provide a summary of evidence of the effects of dermatological treatments, which has been derived using explicit methods widely accepted within science.

Herpes Zoster↗

Non-uniform systematic sampling in stereology.

Non-uniform systematic sampling designs in stereology are studied. Various methods of constructing non-uniform systematic sampling points from prior knowledge of the measurement function are presented. As an example, we consider area estimation from lengths of linear intercepts. The efficiency of two area estimators, based on non-uniform sampling of parallel lines, is compared to that of the classical 2D Cavalieri estimator, based on uniform sampling, in a sample of planar profiles from transverse sections of 41 small myelinated axons. The comparison is based on simulations. It is concluded that for profiles of this type one of the non-uniform sampling schemes is more efficient than the traditional uniform sampling scheme. Other examples where non-uniform systematic sampling may be used are in area estimation from lines emanating from a fixed point, area estimation from concentric circles or spirals and curve length estimation from sweeping lines. It is shown that proportional-to-size sampling is a special case of non-uniform systematic sampling. Finally, the effect of noise in the observations is discussed.

Axons↗

Precision of circular systematic sampling.

In design stereology, many estimators require isotropic orientation of a test probe relative to the object in order to attain unbiasedness. In such cases, systematic sampling of orientations becomes imperative on grounds of efficiency and practical applicability. For instance, the planar nucleator and the vertical rotator imply systematic sampling on the circle, whereas the Buffon-Steinhaus method to estimate curve length in the plane, or the vertical designs to estimate surface area and curve length, imply systematic sampling on the semicircle. This leads to the need for predicting the precision of systematic sampling on the circle and the semicircle from a single sample. There are two main prediction approaches, namely the classical one of G. Matheron for non-necessarily periodic measurement functions, and a recent approach based on a global symmetric model of the covariogram, more specific for periodic measurement functions. The latter approach seems at least as satisfactory as the former for small sample sizes, and it is developed here incorporating local errors. Detailed examples illustrating common stereological tools are included.

Analysis of Variance↗

Mid-trimester ultrasound prediction of gestational age: advantages and systematic errors.

OBJECTIVE: To detect possible sources of bias in ultrasound prediction of gestational age. SUBJECTS AND METHODS: Using the Swedish Medical Birth Registry, 571 617 women were identified who were delivered between 1990 and 1997 and who had obtainable information on last menstrual period and expected date of delivery according to ultrasound. RESULTS: Male fetuses were more likely than females to be judged older than the last menstrual period date suggested at early fetometry. The estimated magnitude of the systematic error by infant gender corresponded to 1.5 days. Similarly, the fetuses of young women, multiparous women, smokers and women with low educational level were at increased risk of being smaller than expected at ultrasound examination in early pregnancy. A strong association was seen between adjustments of expected date of delivery -7 days or more and small-for-gestational age according to ultrasound at birth. Compared to singleton pregnancies, twin pregnancies were more likely to be judged more progressed at ultrasound fetometry than the last menstrual period date suggested. CONCLUSIONS: Compared to last menstrual period estimates, routine ultrasound measurements to predict date of delivery are comparatively reliable but systematic errors are inherent in the method. The erroneous adjusted dates may be due to incorrect measurements or systematic bias (e.g. gender), but they are also likely to reflect early growth restriction (e.g. in the case of maternal smoking and small-for-gestational age). Further studies are needed to investigate whether the systematic errors in ultrasound prediction of gestational age could lead to suboptimal obstetric management in adjusted pregnancies.

Adolescent↗

Systematic reviews of treatment for inflammatory demyelinating neuropathy.

This review describes the progress made in preparing Cochrane systematic reviews of randomized controlled trials for Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), multifocal motor neuropathy (MMN) and the demyelinating neuropathies associated with paraproteins. The discovery of antibodies against myelin and axolemmal glycolipids and proteins has not yet replaced the clinicopathological classification on which treatment trials have been based. Systematic reviews have endorsed the equivalence of plasma exchange (PE) and intravenous immunoglobulin (IVIg) and the lack of efficacy of steroids in GBS. Systematic reviews have also endorsed the value of steroids, PE and IVIg in CIDP but randomized controlled trials have only shown benefit from IVIg in MMN. There is a paucity of evidence concerning the efficacy of treatments in paraproteinaemic demyelinating neuropathy apartment from small trials showing short-term benefit from PE or IVIg. There is a lack of good quality controlled trials of immunosuppressive agents in any of these conditions. As the number of treatment trials increases, Cochrane systematic reviews will be an increasingly valuable resource for summarizing the evidence from randomised controlled trials on which to base clinical practice. They already demonstrate major deficiencies in the existing evidence base.

Glucocorticoids↗

How relevant are the systematic reviews in the cochrane library to emergency medical practice?

STUDY OBJECTIVES: The Cochrane Database of Systematic Reviews (CDSR), one of the databases in the Cochrane Library, is a compilation of regularly updated systematic reviews with meta-analytic summary statistics. We conducted a study of the CDSR to evaluate the relevance of this database to emergency medical practice. METHODS: Using criteria that were determined a priori, 2 reviewers independently screened the titles of 795 completed reviews from the April 2000 CDSR for possible relevance to emergency medicine practice. Five reviewers independently ranked summaries of these reviews for degree of relevance. Agreement was measured using kappa statistics. Disagreements were resolved by consensus or adjudication. RESULTS: Screening of 795 completed reviews identified 136 (17%) as "possibly" and 151 (19%) as "likely" relevant (simple agreement, 74%; kappa=0.82). Further independent assessment indicated 95 (12%) of the 151 "likely" systematic reviews were directly relevant to emergency medicine practice, whereas 44 (6%) were indirectly relevant (simple agreement, 77%; kappa=0.45). Cochrane Review Groups producing the most emergency medicine-relevant systematic reviews included acute respiratory infections (14 [10%]), injuries (14 [10%]), pregnancy and childbirth (13 [10%]), stroke (12 [10%]), and airways (11 [8%]). In contrast, only 1 (0.1%) of the reviews produced by the Heart Review Group was considered directly relevant to emergency medicine practice. CONCLUSION: More than one third of CDSR reviews have some relevance, and 12% are directly relevant, to emergency medical practice or discharge planning. Although certain conditions are well covered, other key emergency medicine areas are not. Emergency physicians should consider the Cochrane Library an important evidence-based resource for emergency medicine therapeutic interventions and should examine ways of increasing the number of reviews relevant to emergency medicine.

Databases, Factual↗

Effectiveness of systematized hepatectomy with Glisson's pedicle transection at the hepatic hilus for small nodular hepatocellular carcinoma: retrospective analysis.

BACKGROUND: The effectiveness of systematized hepatectomy with transection of Glisson's pedicle at the hepatic hilus in patients with small nodular hepatocellular carcinoma (HCC) has not been confirmed. METHODS: Surgical outcomes were reviewed in 204 patients with single nodular HCCs less than 5 cm in greatest diameter, including 68 patients with tumors that showed extranodular growth and 136 patients with tumors that did not, who had undergone curative hepatectomy (partial hepatic resection, n = 114; systematized hepatectomy, n = 90) from 1990 through 1994. RESULTS: The rates of microscopic vascular invasion and intrahepatic metastasis were significantly higher in patients who had single nodular HCCs with extranodular growth (34% and 49%) than in patients who had single nodular HCCs without extranodular growth (13%, P =.001, and 4%, P <.001). The 5-year survival rate in patients who had single nodular HCCs with extranodular growth was significantly greater after systematized hepatectomy (67%) than after partial hepatic resection (21%, P =.0002). Multivariate analysis showed that the type of operation was an independent prognostic factor in patients with single nodular HCCs with extranodular growth (P =.0008). CONCLUSIONS: Systematized hepatectomy with Glisson's pedicle transection at the hepatic hilus should be performed in patients who have single small nodular HCCs with extranodular growth because these tumors often invade within the liver sector containing the tumor.

Aged↗

Systematic versus selective stent placement after superficial femoral artery balloon angioplasty: a multicenter prospective randomized study.

PURPOSE: Outcome with selective or systematic stenting with the Palmaz vascular stent was compared in patients with limb-threatening ischemia or persistent disabling claudication despite medical therapy, with less than 7 cm stenosis or occlusion of the superficial femoral artery. METHODS: This was a multicenter prospective randomized trial with centralized allocation of treatment and independent review of vascular events. The primary end point was presence of more than 50% stenosis at 1-year angiographic follow-up. Secondary end points were survival; occurrence of vascular events in the treated leg; and number of failed procedures, defined as more than 50% stenosis or death at 1 year. RESULTS: Two hundred twenty-seven patients were enrolled in the study, 112 in the selective stent group, and 115 in the systematic stent group. Seventeen patients (15%) in the selective stent group received a stent after suboptimal results of percutaneous transluminal angioplasty. Angiograms for 140 patients were available at 1-year follow-up and demonstrated no statistical difference between the two groups; more than 50% stenosis of the dilated site was noted in 21 of 65 patients (32,3%) in the selective stent group and 26 of 75 patients (34.7%) in the systematic stent group (P =.85, Fisher exact test). Survival in the percutaneous transluminal angioplasty and stent groups was, respectively, 92% and 96% at 1 year, 89% and 93% at 2 years, and 82% and 80% at 4 years (P =.40, log-rank test). Survival free of new vascular events in the treated limb was 77% and 65% at 1 year, 70% and 53% at 2 years, and 57% and 44% at 4 years (P =.017, log-rank test). Number of failed procedures at 1 year was 29 of 86 (33%) and 30 of 89 (34%) (P = 0.9). CONCLUSION: Systematic stenting of short stenosis or occlusion of the superficial femoral artery is not justified. Palmaz vascular stent placement should be reserved for use in patients with suboptimal results of balloon angioplasty.

Aged↗

Quality of systematic reviews used in guidelines for oncology practice.

BACKGROUND: Systematic reviews are an important tool for developing clinical recommendations. Those of high quality assure a good level of confidence on the strength of the recommendations. METHODS: A QUOROM-based checklist was applied to the reviews cited in a sample of guidelines on breast and colon cancer prevention and therapy. The checklist provided a weight for each criterion and a total quality score. Each review was independently evaluated by two reviewers; disagreements were solved by consensus. RESULTS: Eighty reviews (96%) were retrieved and evaluated; 36 focused on breast, and 44 on colorectal cancer. Twenty-three reviews (29%) did not match the definition of systematic review. In 17 (21%) the searching methods were unclear or described elsewhere. Forty (50%) were systematic. Not systematic, low and very low quality reviews accounted for 70% of the total. No review obtained the A+ class score; only 5 (6%) the A- and 7 (9%) the B+. CONCLUSIONS: The results of this assessment provide a sober picture of the quality of the sources used to build guidelines. Oncologists should be aware that they could be relying on poor underlying documents. Writing groups should be aware of methodological problems, and should consult the existing manuals for the preparation of guidelines.

Evidence-Based Medicine↗

Adapting and disseminating effective public health interventions in another country: towards a systematic approach.

BACKGROUND: Public health interventions that have proven effective in one country, are often adapted and disseminated in other countries. However, the process by which effective interventions are chosen for adaptation and dissemination in another country is often not conducted systematically. METHODS: We propose a more systematic approach and describe the main steps that have to be taken in the assessment of the usefulness of effective interventions in another national context. RESULTS: The following steps are proposed. Step 0: Point out the most relevant areas in public health (this is a collaborative effort by policy makers, scientists and practitioners). Step 1: Identification of potentially effective interventions (through systematic literature searches). Step 2: Assessing the levels of evidence and grades of recommendation for adoption. Step 3: Can the results of the trials be generalized to the national situation? Step 4: Can the intervention be implemented in the national situation? CONCLUSION: A more systematic approach to the adaptation and dissemination can be adopted. The basic steps described should be worked out in more detail before they can be used in practice.

Communication↗

Systematic health, environment and safety activities: do they influence occupational environment, behaviour and health?

This study investigated the relationships between systematic health, environment and safety (HES) activities (as defined by Norway's Internal Control Regulation), the working environment, and workers' health-related behaviour and health. A questionnaire on systematic HES activities was answered by 237 managers of motor vehicle repair garages. A further questionnaire, on the working environment, health-related behaviour and health, was answered by workers (n = 2174) from the same garages. Using regression analysis, systematic HES activities were positively and significantly correlated with the following separate outcome variables, measured at an individual level: satisfaction with HES activities, physical working environment, social support, HES-related management support, health-related support, and control and workers' participation in activities related to occupational health. Workers at garages with systematic HES activities reported fewer musculoskeletal symptoms. Firm conclusions on the direction of causality are difficult to draw because of the cross-sectional design.

Accidents, Occupational↗