How to Address Heterogeneity Before a Systematic Review Begins
J R Soc Med. 2003 Mar; 96(3): 118–121.
Five steps to conducting a systematic review
Regina Kunz
one German Cochrane Centre, Freiburg and Section of Nephrology, Charité, Berlin, Germany
Jos Kleijnen
2 Centre for Reviews and Dissemination, York, Britain
Gerd Antes
iii German Cochrane Eye, Freiburg, Germany
Systematic reviews and meta-analyses are a fundamental 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 agglomeration of insignificant findings suddenly get pregnant? This paper, along with a bookone that goes into more detail, demystifies these and other related intrigues.
A review earns the adjective systematic if it is based on a conspicuously formulated question, identifies relevant studies, appraises their quality and summarizes the evidence by use of explicit methodology. It is the explicit and systematic approach that distinguishes systematic reviews from traditional reviews and commentaries. Whenever we use the term review in this paper it will mean a systematic review. Reviews should never be done in any other style.
In this paper we provide a pace-by-footstep explanation—there are just 5 steps—of the methods behind reviewing, and the quality elements inherent in each step (Box 1). For purposes of analogy we use a published review concerning the safety of public h2o fluoridation, but we must emphasize that our subject is review methodology, not fluoridation.
EXAMPLE: Safe OF PUBLIC WATER FLUORIDATION
You are a public health professional person in a locality that has public water fluoridation. For many years, your colleagues and you lot have believed that it improves dental wellness. Recently in that location has been pressure from diverse involvement groups to consider the safety of this public wellness intervention because they fright that it is causing cancer. Public health decisions take been based on professional judgment and practical feasibility without explicit consideration of the scientific bear witness. (This was yesterday; today the evidence is available in a York review2 , 3, identifiable on MEDLINE through the freely attainable PubMed clinical queries interface [http://world wide web.ncbi.nlm.nib.gov/entrez/query/static/clinical.html], under 'systematic reviews'.)
STEP 1: FRAMING THE QUESTION
The research question may initially be stated every bit a query in costless class but reviewers prefer to pose it in a structured and explicit fashion. The relations between various components of the question and the construction of the research design are shown in Figure 1. This paper focuses only on the question of rubber related to the outcomes described beneath.
Structured questions for systematic reviews and relations betwixt question components in a comparative study
Gratis-form question
Is it safe to provide population-wide drinking water fluoridation to forestall caries?
Structured question
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The populations—Populations receiving drinking h2o sourced through a public h2o supply
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The interventions or exposures—Fluoridation of drinking water (natural or bogus) compared with not-fluoridated h2o
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The outcomes—Cancer is the primary outcome of interest for the debate in your health authorization
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The written report designs—Comparative studies of whatsoever design examining the harmful outcomes in at to the lowest degree two population groups, i with fluoridated drinking water and the other without. Harmful outcomes can be rare and they may develop over a long time. There are considerable difficulties in designing and conducting safety studies to capture these outcomes, since a large number of people need to be observed over a long menstruum. These circumstances demand observational, not randomized studies. With this groundwork, systematic reviews on prophylactic take to include evidence from studies with a range of designs.
STEP 2: IDENTIFYING RELEVANT PUBLICATIONS
To capture every bit many relevant citations every bit possible, a wide range of medical, ecology and scientific databases were searched to place primary studies of the furnishings of h2o fluoridation. The electronic searches were supplemented by hand searching of Index Medicus and Excerpta Medica back to 1945. Furthermore, various internet engines were searched for web pages that might provide references. This effort 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 main studies in man that direct related to fluoride in drinking h2o supplies, comparing at least two groups. These criteria excluded 481 studies and left 254 in the review. They came from thirty countries, published in 14 languages betwixt 1939 and 2000. Of these studies 175 were relevant to the question of condom, of which 26 used cancer equally an issue.
Pace 3: ASSESSING Report QUALITY
Design threshold for written report pick
Acceptable report blueprint equally a marker of quality, is listed as an inclusion benchmark in Box 1. This approach is most applicable when the main source of evidence is randomized studies. All the same, randomized studies are almost incommunicable to deport at community level for a public health intervention such equally water fluoridation. Thus, systematic reviews assessing the safe of such interventions have to include evidence from a broader range of study designs. Consideration of the type and corporeality of research probable to be available led to inclusion of comparative studies of any design. In this way, selected studies provided information nearly the harmful effects of exposure to fluoridated water compared with non-exposure.
Quality assessment of safety studies
Later on studies of an acceptable design take been selected, their in-depth assessment for the risk of various biases allows us to gauge the quality of the evidence in a more refined way. Biases either exaggerate or underestimate the 'true' upshot of an exposure. The objective of the included studies was to compare groups exposed to fluoridated drinking h2o and those without such exposure for rates of undesirable outcomes, without bias. Safety studies should define exposures and outcomes in such a way that the risk of misclassification is minimized. The exposure is likely to be more accurately ascertained if the report was prospective rather than retrospective and if information technology was started soon afterwards h2o fluoridation rather than later. The outcomes of those developing cancer (and remaining free of cancer) are likely to be more accurately ascertained if the follow-up was long and if the assessment was blind to exposure condition.
When examining how the outcome of exposure on outcome was established, reviewers assessed whether the comparison groups were similar in all respects other than their exposure to fluoridated water. This is because the other differences may be related to the outcomes of interest contained of the drinking-h2o fluoridation, and this would bias the comparison. For case, if the people exposed to fluoridated water had other risk factors that made them more prone to have cancer, the credible clan between exposure and result might be explained past the more frequent occurrence of these factors amid the exposed group. The technical word for such defects is confounding. In a randomized study, confounding factors are expected to exist roughly equally distributed betwixt groups. In observational studies their distribution may be unequal. Primary researchers can statistically adjust for these differences, when estimating the event of exposure on outcomes, by utilise of multivariable modelling.
Put but, utilise of a prospective design, robust ascertainment of exposure and outcomes, and control for confounding are the generic issues one would look for in quality cess of studies on safety. Consequently, studies may range from satisfactorily meeting quality criteria, to having some deficiencies, to non meeting the criteria at all, and they tin can be assigned to one of three prespecified quality categories equally shown in Tabular array 1. A quality bureaucracy can and then exist developed, based on the degree to which studies comply with the criteria. None of the studies on cancer were in the high-quality category, but this was because randomized studies were non-existent and control for confounding was not always ideal in the observational studies. There were 8 studies of moderate quality and 18 of low quality.
Table 1
Description of quality assessment of studies on safety of public h2o fluoridation
| Quality categories | High | Moderate | Low |
|---|---|---|---|
| Prospective blueprint | Prospective | Prospective | Prospective or retrospective |
| Ascertainment of exposure | Report began inside ane year of fluoridation | Study began within 3 years of fluoridation | Written report began >three years after fluoridation |
| Ascertainment of issue | Follow-up for at least 5 years and bullheaded cess | Long follow-up and bullheaded cess | Short follow-upwardly and unblinded cess |
| Command for confounding | Adjustment for at least three confounding factors (or apply of randomization) | Adjustment for at least one confounding factor | No adjustment for confounding factors |
STEP iv: SUMMARIZING THE Testify
To summarize the show from studies of variable design and quality is not easy. The original review3 provides details of how the differences between study results were investigated and how they were summarized (with or without meta-analysis). 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, ten examined all-cause cancer incidence or mortality, in 22 analyses. Of these, eleven analyses establish a negative clan (fewer cancers due to exposure), ix found a positive i and 2 found no association. Simply ii studies reported statistically meaning differences. Thus no clear association between h2o fluoridation and increased cancer incidence or mortality was apparent. Bone/joint and thyroid cancers were of item concern because of fluoride uptake past these organs. Neither the 6 studies of osteosarcoma nor the ii studies of thyroid cancer and h2o fluoridation revealed significant differences. Overall no association was detected between h2o fluoridation and mortality from any cancer. These findings were also borne out in the moderate-quality subgroup of studies.
Step 5: INTERPRETING THE FINDINGS
In the fluoridation example, the focus was on the safety of a community-based public wellness intervention. The generally low quality of available studies means that the results must be interpreted with caution. However, the elaborate efforts in searching an unusually large number of databases provide some safeguard against missing relevant studies. Thus the bear witness summarized in this review is likely to be every bit practiced as it will arrive the foreseeable future. Cancer was the harmful outcome of nigh interest in this instance. No association was found betwixt exposure to fluoridated water and specific cancers or all cancers. The interpretation of the results may be mostly limited considering of the depression quality of studies, but the findings for the cancer outcomes are supported past the moderate-quality studies.
RESOLUTION
After having spent some time reading and understanding the review, you are impressed by the sheer corporeality of published piece of work relevant to the question of safety. Nonetheless, you are somewhat disappointed past the poor quality of the chief studies. Of course, test of safety merely makes sense in a context where the intervention has some beneficial effect. Benefit and harm have to be compared to provide the basis for decision making. On the effect of the benign effect of public water fluoridation, the review3 reassures y'all that the health authority was right in judging that fluoridation of drinking h2o prevents caries. From the review y'all also discovered that dental fluorosis (mottled teeth) was related to concentration of fluoride. When the involvement groups raise the issue of condom again, you will exist able to declare that at that place is no evidence to link cancer with drinking-water fluoridation; even so, you lot will have to come up clean most the risk of dental fluorosis, which appears to exist dose dependent, and you lot may want to measure the fluoride concentration in the water supply and share this data with the interest groups.
The ability to quantify the condom concerns of your population through a review, admitting from studies of moderate to low quality, allows your health say-so, the politicians and the public to consider the balance between beneficial and harmful effects of water fluoridation. Those who come across the prevention of caries as of primary importance volition favour fluoridation. Others, worried about the disfigurement of mottled teeth, may prefer other ways of fluoride administration or even occasional treatment for dental caries. Any the opinions on this thing, yous are able to reassure all parties that at that place is no show that fluoridation of drinking water increases the take chances of cancer.
CONCLUSION
With increasing focus on generating guidance and recommendations for do through systematic reviews, healthcare professionals need to empathize the principles of preparing such reviews. Here we have provided a brief step-by-step explanation of the principles. Our bookane describes them in detail.
References
Manufactures from Journal of the Royal Society of Medicine are provided here courtesy of Royal Social club of Medicine Press
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Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC539417/
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