While all the current systems of evidence classification have flaws, they all emphasize essential features of a study that could contribute meaningfully to evaluation and care of patients with epilepsy. This section outlines items that can, and should, be incorporated in imaging studies (). STROBE (http://www.strobe-statement.org
) and CONSORT (http://www.bmj.com/content/340/bmj.c869.full
) are efforts to help standardize and improve presentation of data from observational studies and randomized trials, elements of which may also help inform planning and reporting of imaging studies. It may be possible to conduct a “Class 1” epidemiological study on prognosis for developing intractable epilepsy based on standardized imaging if given enough time (Berg, 2009
). However, it is not likely that broad population, randomized imaging trials will be conducted with control populations for epilepsy surgery. We propose below study designs and elements that address many of the current difficulties in the epilepsy imaging literature. Studies that contain these essential elements should be strongly considered as meeting best clinical research practice that informs clinical care.
Investigators must clearly define the clinical or pathophysiological question (e.g. comparison with EEG, pathology, surgical outcome, IAT, other imaging) and design a study to answer it. The patients and data should be prospectively obtained with clearly defined populations and study selection criteria, in agreed diagnostic categories. As patients in imaging/neurophysiology epilepsy studies are unlikely to be randomized, the imaging modality should be applied to all patients with the caregiver blinded, when equipoise is present, to study result. The image analysis methods and measures should be clearly defined. Preferably the image data should be assessed by objective, quantitative measures, or where not possible, by expert blinded raters, with a separate image set used to assess interpretative reliability. All assessments need to be blinded to patient identity from the rater, and when equipoise is present, from the caregiver.
Studies need to contain a sufficiently large patient and control population and be powered to accommodate heterogeneity and allow statistically-valid subgroup analyses of more homogeneous sub-populations. Where diagnostic considerations are paramount, pathological confirmation should be provided in surgical series; these data should be analyzed on image findings not pathology findings. Where outcome is paramount a prolonged (at least one year) and complete follow-up should be made; outcomes should be defined and ascertained by a person without a vested interest in the outcome.
Control populations are the hallmark of any clinical study yet remain problematic for epilepsy. Some studies more readily lend themselves to normal control populations and need to be used whenever possible. Other studies will only be conducted in patient populations, where the next best option is to examine the data between those who undergo a procedure in question or who do not have the procedure. In this setting comment can not be made, particularly regarding outcomes, on those who did not have the procedure.
Ideally the experimental data will not be used in the decision process. Where ethical restraints prohibit such a design one can make decision without the data then reconsider the clinical decision with the data provided (Change in practice model). In these circumstances meticulous documentation of how the information altered decision making would need to be provided. For example, one scenario to establish the utility of a new test is to apply the new test to cases in whom a clinical answer is not clear (e.g. non-lesional) and then to determine if new information is provided that changes the plan (proceed vs. not proceed to surgery) and then whether it leads to a good outcome. Other possible models are to set up a sham committee with the two sets of data, or to set up a study where one center employs the new technology and the other does not in order to see if the new technology influences outcomes presuming comparable patient populations and, where relevant, surgical approach and expertise. In this circumstance data would need to be examined to assure the patient populations are comparable.
The investigators should provide a data table showing results for each subject explicitly. The presentation of data allows independent assessment, facilitates comparison of data, and facilitates future meta-analysis. The data should be analyzed with the appropriate statistical test, which will usually be some variant of ‘validity:’ sensitivity and specificity, and positive predictive value. It is also important to acknowledge limitations including potential sources of referral bias. Methods should be clear, and when possible with standardization protocols, in order to facilitate study replication and pooling of data across specialty centers. A broad range and spectrum of patients necessary for class one diagnostic and outcome studies are unlikely to derive from any single center. If a different method is used, comparison to more common methods should be included with a determination of positive contribution and redundancy made.
Potential conflict of interest needs to be addressed in guideline development. In addition to relationships with industry, it is important to consider that investigators may have substantial clinical income, grant support, or academic publications and prestige related to particular techniques.