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J R Soc Med. 2003 Mar; 96(3): 118–121.
5 steps to conducting a systematic review
Regina Kunz
one German Cochrane Centre, Freiburg and Department of Nephrology, Charité, Berlin, Germany
Jos Kleijnen
2 Centre for Reviews and Dissemination, York, United kingdom of great britain and northern ireland
Gerd Antes
3 German Cochrane Center, Freiburg, Germany
Systematic reviews and meta-analyses are a primal element of prove-based healthcare, yet they remain in some ways mysterious. Why did the authors select certain studies and reject others? What did they do to pool results? How did a bunch of insignificant findings suddenly get meaning? This paper, along with a book1 that goes into more detail, demystifies these and other related intrigues.
A review earns the adjective systematic if it is based on a clearly formulated question, identifies relevant studies, appraises their quality and summarizes the bear witness past employ of explicit methodology. It is the explicit and systematic approach that distinguishes systematic reviews from traditional reviews and commentaries. Whenever we utilize the term review in this paper it volition mean a systematic review. Reviews should never exist done in whatever other way.
In this paper we provide a step-by-step caption—there are just five steps—of the methods behind reviewing, and the quality elements inherent in each footstep (Box one). For purposes of illustration we apply a published review concerning the safe of public water fluoridation, simply we must emphasize that our discipline is review methodology, not fluoridation.
Example: SAFETY OF PUBLIC Water FLUORIDATION
You are a public health professional person in a locality that has public h2o fluoridation. For many years, your colleagues and you have believed that it improves dental health. Recently there has been pressure from various interest groups to consider the safety of this public wellness intervention because they fear that it is causing cancer. Public health decisions take been based on professional person judgment and practical feasibility without explicit consideration of the scientific evidence. (This was yesterday; today the evidence is bachelor in a York reviewtwo , 3, identifiable on MEDLINE through the freely accessible PubMed clinical queries interface [http://world wide web.ncbi.nlm.nib.gov/entrez/query/static/clinical.html], under 'systematic reviews'.)
Pace 1: FRAMING THE QUESTION
The enquiry question may initially be stated as a query in gratuitous form simply reviewers prefer to pose it in a structured and explicit way. The relations between various components of the question and the structure of the research design are shown in Effigy i. This paper focuses only on the question of safety related to the outcomes described below.
Structured questions for systematic reviews and relations between question components in a comparative report
Free-form question
Is it safety to provide population-broad drinking water fluoridation to preclude caries?
Structured question
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The populations—Populations receiving drinking water sourced through a public h2o supply
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The interventions or exposures—Fluoridation of drinking h2o (natural or artificial) compared with non-fluoridated water
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The outcomes—Cancer is the principal event of interest for the debate in your wellness potency
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The written report designs—Comparative studies of whatever blueprint examining the harmful outcomes in at least two population groups, one with fluoridated drinking water and the other without. Harmful outcomes tin be rare and they may develop over a long fourth dimension. There are considerable difficulties in designing and conducting safe studies to capture these outcomes, since a large number of people demand to exist observed over a long menses. These circumstances demand observational, not randomized studies. With this background, systematic reviews on safety accept to include evidence from studies with a range of designs.
STEP two: IDENTIFYING RELEVANT PUBLICATIONS
To capture every bit many relevant citations equally possible, a wide range of medical, environmental and scientific databases were searched to place primary studies of the effects of water fluoridation. The electronic searches were supplemented by hand searching of Alphabetize Medicus and Excerpta Medica back to 1945. Furthermore, diverse internet engines were searched for spider web pages that might provide references. This endeavor resulted in 3246 citations from which relevant studies were selected for the review. Their potential relevance was examined, and 2511 citations were excluded as irrelevant. The full papers of the remaining 735 citations were assessed to select those principal studies in human being that directly related to fluoride in drinking water supplies, comparison at least ii groups. These criteria excluded 481 studies and left 254 in the review. They came from 30 countries, published in xiv languages between 1939 and 2000. Of these studies 175 were relevant to the question of prophylactic, of which 26 used cancer as an outcome.
Footstep 3: ASSESSING STUDY QUALITY
Pattern threshold for study pick
Adequate study design equally a marker of quality, is listed as an inclusion benchmark in Box i. This arroyo is almost applicable when the main source of evidence is randomized studies. However, randomized studies are nearly impossible to conduct at community level for a public health intervention such every bit water fluoridation. Thus, systematic reviews assessing the safety of such interventions have to include evidence from a broader range of written report designs. Consideration of the type and amount of inquiry likely to be available led to inclusion of comparative studies of any design. In this way, selected studies provided information about the harmful effects of exposure to fluoridated water compared with not-exposure.
Quality cess of safe studies
After studies of an acceptable design have been selected, their in-depth assessment for the gamble of diverse biases allows usa to approximate the quality of the bear witness in a more than refined way. Biases either exaggerate or underestimate the 'true' effect of an exposure. The objective of the included studies was to compare groups exposed to fluoridated drinking water and those without such exposure for rates of undesirable outcomes, without bias. Rubber studies should ascertain exposures and outcomes in such a fashion that the run a risk of misclassification is minimized. The exposure is likely to be more accurately ascertained if the study was prospective rather than retrospective and if information technology was started soon after water fluoridation rather than afterwards. The outcomes of those developing cancer (and remaining free of cancer) are likely to be more than accurately ascertained if the follow-up was long and if the assessment was blind to exposure condition.
When examining how the effect of exposure on upshot was established, reviewers assessed whether the comparison groups were similar in all respects other than their exposure to fluoridated h2o. This is because the other differences may exist related to the outcomes of interest independent of the drinking-water fluoridation, and this would bias the comparison. For case, if the people exposed to fluoridated water had other risk factors that made them more than prone to take cancer, the apparent association between exposure and outcome might exist explained past the more frequent occurrence of these factors among the exposed group. The technical give-and-take for such defects is confounding. In a randomized study, confounding factors are expected to be roughly every bit distributed between groups. In observational studies their distribution may exist unequal. Primary researchers tin statistically adjust for these differences, when estimating the outcome of exposure on outcomes, past use of multivariable modelling.
Put simply, use of a prospective blueprint, robust observation of exposure and outcomes, and control for misreckoning are the generic issues i would await for in quality cess of studies on condom. Consequently, studies may range from satisfactorily meeting quality criteria, to having some deficiencies, to not meeting the criteria at all, and they can be assigned to one of three prespecified quality categories as shown in Table ane. A quality hierarchy can then be adult, based on the degree to which studies comply with the criteria. None of the studies on cancer were in the loftier-quality category, but this was because randomized studies were non-existent and command for confounding was not always ideal in the observational studies. In that location were 8 studies of moderate quality and 18 of low quality.
Table ane
Description of quality assessment of studies on safety of public water fluoridation
| Quality categories | High | Moderate | Depression |
|---|---|---|---|
| Prospective pattern | Prospective | Prospective | Prospective or retrospective |
| Ascertainment of exposure | Written report began within ane yr of fluoridation | Study began within iii years of fluoridation | Report began >three years later fluoridation |
| Ascertainment of outcome | Follow-up for at least five years and blind assessment | Long follow-upwards and blind assessment | Short follow-up and unblinded assessment |
| Command for misreckoning | Adjustment for at least iii confounding factors (or utilise of randomization) | Aligning for at least one confounding cistron | No adjustment for confounding factors |
STEP 4: SUMMARIZING THE Testify
To summarize the evidence from studies of variable pattern and quality is not piece of cake. The original review3 provides details of how the differences betwixt report results were investigated and how they were summarized (with or without meta-assay). This paper restricts itself to summarizing the findings narratively. The association betwixt exposure to fluoridated water and cancer in full general was examined in 26 studies. Of these, 10 examined all-crusade cancer incidence or mortality, in 22 analyses. Of these, eleven analyses found a negative association (fewer cancers due to exposure), nine found a positive one and 2 found no association. Simply ii studies reported statistically significant differences. Thus no clear association between h2o fluoridation and increased cancer incidence or mortality was apparent. Bone/joint and thyroid cancers were of detail business organisation because of fluoride uptake by these organs. Neither the 6 studies of osteosarcoma nor the 2 studies of thyroid cancer and h2o fluoridation revealed significant differences. Overall no association was detected between water fluoridation and bloodshed from any cancer. These findings were also borne out in the moderate-quality subgroup of studies.
STEP 5: INTERPRETING THE FINDINGS
In the fluoridation case, the focus was on the safety of a community-based public health intervention. The generally low quality of available studies means that the results must be interpreted with caution. Even so, the elaborate efforts in searching an unusually large number of databases provide some safeguard against missing relevant studies. Thus the evidence summarized in this review is likely to be equally adept as it will make it the foreseeable futurity. Cancer was the harmful outcome of most interest in this instance. No clan was found between exposure to fluoridated water and specific cancers or all cancers. The interpretation of the results may be more often than not limited because of the low quality of studies, but the findings for the cancer outcomes are supported by the moderate-quality studies.
RESOLUTION
After having spent some time reading and understanding the review, you are impressed by the sheer corporeality of published work relevant to the question of safety. However, you lot are somewhat disappointed by the poor quality of the primary studies. Of course, examination of safety only makes sense in a context where the intervention has some benign effect. Benefit and impairment accept to be compared to provide the ground for decision making. On the outcome of the beneficial effect of public water fluoridation, the reviewiii reassures you that the wellness authorisation was correct in judging that fluoridation of drinking h2o prevents caries. From the review yous also discovered that dental fluorosis (mottled teeth) was related to concentration of fluoride. When the interest groups raise the issue of condom again, you will be able to declare that at that place is no evidence to link cancer with drinking-water fluoridation; yet, you will take to come clean most the risk of dental fluorosis, which appears to be dose dependent, and you lot may want to measure the fluoride concentration in the water supply and share this information with the interest groups.
The power to quantify the safety concerns of your population through a review, admitting from studies of moderate to low quality, allows your wellness authorisation, the politicians and the public to consider the balance between beneficial and harmful effects of h2o fluoridation. Those who run into the prevention of caries as of principal importance will favour fluoridation. Others, worried most the disfigurement of mottled teeth, may adopt other means of fluoride administration or even occasional treatment for dental caries. Whatsoever the opinions on this matter, you are able to reassure all parties that at that place is no evidence that fluoridation of drinking water increases the risk of cancer.
CONCLUSION
With increasing focus on generating guidance and recommendations for exercise through systematic reviews, healthcare professionals demand to understand the principles of preparing such reviews. Here we have provided a brief step-by-step caption of the principles. Our book1 describes them in detail.
References
Articles from Journal of the Imperial Society of Medicine are provided here courtesy of Imperial Society of Medicine Press
Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC539417/
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