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Notes on the use of Methodology Checklist 3: Cohort studies
The studies covered by this checklist are designed to answer questions of the type “What are the effects of this exposure?”, It relates to studies that compare a group of people with a particular exposure with another group who either have not had the exposure, or have a different level of exposure. Cohort studies may be prospective (where the exposure is defined and subjects selected before outcomes occur), or retrospective (where exposure is assessed after the outcome is known, usually by the examination of medical records). Retrospective studies are generally regarded as a weaker design, and should not receive a "++" rating.
Section 1 identifies the study, the reviewer, the guideline for which the paper is being considered as evidence, and the key question(s) it is expected to address. The reviewer is asked to consider a series of aspects of cohort study design and to make a judgement as to how well the current study meets this criterion. Each relates to an aspect of methodology that research has shown to be likely to influence the conclusions of a study.
Because of the potential complexity and subtleties of the design of this type of study, there are comparatively few criteria that automatically rule out use of a study as evidence. It is more a matter of increasing confidence in the strength of association between exposure and outcome by identifying how many aspects of good study design are present, and how well they have been tackled. A study that fails to address or report on more than one or two of the questions addressed below should almost certainly be rejected.
For each question in this section you should use one of the following to indicate how well it has been addressed in the study:
1.1 The study addresses an appropriate and clearly focused question?
Unless a clear and well defined question is specified, it will be difficult to assess how well the study has met its objectives or how relevant it is to the question you are trying to answer on the basis of its conclusions.
1.2 The two groups being studied are selected from source populations that are comparable in all respects other than the factor under investigation.
It is important that the two groups selected for comparison are as similar as possible in all characteristics except for their exposure status, or the presence of specific prognostic factors or prognostic markers relevant to the study in question. If the study does not include clear definitions of the source populations and eligibility criteria for participants it should be rejected.
1.3 The study indicates how many of the people asked to take part did so, in each of the groups being studied.
The participation rate is defined as the number of study participants divided by the number of eligible subjects, and should be calculated separately for each branch of the study. A large difference in participation rate between the two arms of the study indicates that a significant degree of selection bias may be present, and the study results should be treated with considerable caution.
1.4 The likelihood that some eligible subjects might have the outcome at the time of enrolment is assessed and taken into account in the analysis?
If some of the eligible subjects, particularly those in the unexposed group, already have the outcome at the start of the trial the final result will be biased. A well conducted study will attempt to estimate the likelihood of this occurring, and take it into account in the analysis through the use of sensitivity studies or other methods.
1.5 What percentage of individuals or clusters recruited into each arm of the study dropped out before the study was completed?
The number of patients that drop out of a study should give concern if the number is very high. Conventionally, a 20% drop out rate is regarded as acceptable, but in observational studies conducted over a lengthy period of time a higher drop out rate is to be expected. A decision on whether to downgrade or reject a study because of a high drop out rate is a matter of judgement based on the reasons why people dropped out, and whether drop out rates were comparable in the exposed and unexposed groups. Reporting of efforts to follow up participants that dropped out may be regarded as an indicator of a well conducted study.
1.6 Comparison is made between full participants and those lost to follow-up, by exposure status.
For valid study results, it is essential that the study participants are truly representative of the source population. It is always possible that participants who dropped out of the study will differ in some significant way from those who remained part of the study throughout. A well conducted study will attempt to identify any such differences between full and partial participants in both the exposed and unexposed groups. Any indication that differences exist, should lead to the study results being treated with caution.
1.7 The outcomes are clearly defined.
Once enrolled in the study, participants should be followed until specified end points or outcomes are reached. In a study of the effect of exercise on the death rates from heart disease in middle aged men, for example, participants might be followed up until death, or until reaching a predefined age. If outcomes and the criteria used for measuring them are not clearly defined, the study should be rejected.
1.8 The assessment of outcome is made blind to exposure status
If the assessor is blinded to which participants received the exposure, and which did not, the prospects of unbiased results are significantly increased. Studies in which this is done should be rated more highly than those where it is not done, or not done adequately.
1.9 Where blinding was not possible, there is some recognition that knowledge of exposure status could have influenced the assessment of outcome.
Blinding is not possible in many cohort studies. In order to asses the extent of any bias that may be present, it may be helpful to compare process measures used on the participant groups - e.g. frequency of observations, who carried out the observations, the degree of detail and completeness of observations. If these process measures are comparable between the groups, the results may be regarded with more confidence.
1.10 The measure of assessment of exposure is reliable.
A well conducted study should indicate how the degree of exposure or presence of prognostic factors or markers was assessed. Whatever measures are used must be sufficient to establish clearly that participants have or have not received the exposure under investigation and the extent of such exposure, or that they do or do not possess a particular prognostic marker or factor. Clearly described, reliable measures should increase the confidence in the quality of the study.
1.11 Evidence from other sources is used to demonstrate that the method of outcome assessment is valid and reliable.
The primary outcome measures used should be clearly stated in the study. If the outcome measures are not stated, or the study bases its main conclusions on secondary outcomes, the study should be rejected. Where outcome measures require any degree of subjectivity, some evidence should be provided that the measures used are reliable and have been validated prior to their use in the study.
1.12 Exposure level or prognostic factor is assessed more than once.
Confidence in data quality should be increased if exposure
level is measured more than once in the course of the study. Independent
assessment
by
more than one investigator is preferable.
1.13 The main potential confounders are identified and taken
into account adequately in the design and analysis.
Confounding is the distortion of a link between exposure and outcome by another factor that is associated with both exposure and outcome. The possible presence of confounding factors is one of the principal reasons why observational studies are not more highly rated as a source of evidence. The report of the study should indicate which potential confounders have been considered, and how they have been assessed or allowed for in the analysis. Clinical judgement should be applied to consider whether all likely confounders have been considered. If the measures used to address confounding are considered inadequate, the study should be downgraded or rejected, depending on how serious the risk of confounding is considered to be. A study that does not address the possibility of confounding should be rejected.
1.14 Confidence intervals are provided.
Confidence limits are the preferred method for indicating the precision of statistical results, and can be used to differentiate between an inconclusive study and a study that shows no effect. Studies that report a single value with no assessment of precision should be treated with extreme caution.
Section 2 relates to the overall assessment of the paper. It starts by rating the methodological quality of the study, based on your responses in Section 1 and using the following coding system:
| ++ | All or most of the
criteria have been fulfilled. Where they have not been fulfilled the conclusions of the study or review are thought very unlikely to alter. |
| + | Some of the criteria
have been fulfilled. Those criteria that have not been fulfilled or not adequately described are thought unlikely to alter the conclusions. |
| - | Few or no criteria
fulfilled The conclusions of the study are thought likely or very likely to alter. |
The code allocated here, coupled with the study type, will decide the level of evidence that this study provides.
The aim of the other questions in this section is to summarise your view of the quality of this study and its applicability to the patient group targeted by the guideline you are working on.
Section 3 asks you to summarise key points about the study that will be added to an evidence table at the next stage of the process. It is important that you complete this section as fully as possible, and include actual data from the study wherever relevant.