ReviewSeizure diaries for clinical research and practice: Limitations and future prospects
Highlights
► Clinical care and most epilepsy trials depend upon seizure counts in diaries. ► Diaries are potentially flawed by inaccurate seizure counts. ► Electronic or on-line diaries can improve accuracy of information collection. ► Analysis of disadvantages and validation are yet to be done.
Introduction
Most clinical trials of epilepsy therapies include seizure frequency, as documented on calendar diaries, as a primary outcome variable. This places self-reported diaries at a pinnacle of importance in the development of new treatments for epilepsy, but little information exists on the accuracy or validity of these tools. On April 30, 2011, the National Institutes of Neurological Diseases and Stroke (NINDS) of the United States National Institutes of Health sponsored a conference on clinical trials in the field of epilepsy, at which seizure diaries were discussed. This article reviews seizure diaries as they now exist and possible directions for the near future.
Diaries are a form of so-called patient‐reported outcomes [33]. The Food and Drug Administration (FDA) has provided guidance, in general, on the development of PROs [13]. A review of patient‐reported outcomes (PROs) in epilepsy [35] listed 61 articles involving design and validation of PROs, including scales for Quality of Life, Seizure Severity and Psychosocial Inventories but none analyzing diaries, which is perhaps the most fundamental PRO. Under ideal circumstances, diaries developed for research and clinical trials would also be useful for direct patient care [15]. Seizure diaries have already been found to be useful for patient-based prediction of subsequent seizures [19]. However, diaries designed primarily for clinical care or seizure prediction are not the subject of this review.
Section snippets
What information should be recorded in a seizure diary?
Before using a seizure diary, subjects need to prospectively describe and codify their various seizure types, in conjunction with study organizers. Patients have the capability of naming their own seizures as they perceive them. For example, seizure type “A” might be described as a feeling of déjà vu; type “B” would be representative of déjà vu followed by confusion, lip-smacking and fumbling; and type “C” would reflect an event of loss of consciousness with falling and shaking. Subjects will
Potential problems with seizure diaries
Table 1 lists the potential problems with interpretation of seizure diaries.
Entering information in diaries requires at least moderate intellectual capability and literacy, which is not present in all patients with epilepsy. However, the increasing penetration of smartphones indicates that most people will have usable input platform in the near future. Studies restricted to those capable of using paper or electronic diaries may introduce selection bias into the trials. Caregivers can assist
Electronic diaries
Electronic diaries provide an alternative to the traditional paper-based seizure diaries. These may be implemented on dedicated handheld devices or as software loaded on a standard smartphone or another commercially available device. Such devices potentially allow programming to improve data validity, real-time transmission of data, reminders to subjects, and other features. However, handheld devices and smartphones may also be lost, although some allow uploads of data when patients are
Seizure diaries in pediatric populations
Use of seizure diaries can be challenging in the pediatric population. First, children with epilepsy may be more likely than adults to have multiple seizure types. Accurate description, categorization and labeling of each seizure type (as described above) are especially crucial for children. Since younger children may not have the cognitive capacity to recognize and report seizures, the data collection must be done by caregiver's observation. Children often have multiple caregivers (parents,
Epilepsy diaries for clinical practice
Two web-based diaries have recently come into clinical use for people with epilepsy, My Epilepsy Diary by Irody, Inc. at epilepsy.com and Seizure Tracker at SeizureTracker.com. Both of these diaries are free, nonprofit services for the epilepsy community. As of March, 2012, My Epilepsy Diary had 13,052 user accounts, two-thirds of which were in the United States, 571,504 logged transactions, 86,840 seizure events, 41,070 reported side effects, and 169,513 medication-related (compliance) events.
Epilepsy diaries for research
Communication and data storage in modern times increasingly involves electronic rather than written data entry and preservation. Computer databases for tracking clinical trials have been available for decades, although not necessarily with primary data entry by the study participants. Electronic data entry is now beginning to be used without concurrent paper diaries, since translation of paper to electronic diaries increases work and introduces translation errors.
Potential advantages and
View from industry
FDA approval of a new medication or high-risk therapeutic device requires at least one adequately controlled randomized clinical trial. The manufacturers of drugs and devices are very aware of the use of medical diaries for PROs that may provide key outcome data for pivotal trials. Advisors to industry will consider whether a diary has been validated against conventional standards and whether it provides accurate as well as precise information. A diary with missing or inaccurate information,
Future directions
Predicting can be hazardous. In 1949, Popular Mechanics asserted that “Computers in the future may weigh no more than 1.5 tons.” (Wikipedia). Speculation about the use of on-line information systems in medicine will likely be as wide of the mark as was the Popular Mechanics prediction. Two trends, however, are likely for the near future: links to biosensors and electronic diaries for clinical trials.
Biosensors can be linked to on-line diaries, in order to automatically collect information about
Recommendations for clinical research
The diary subgroup attending the NINDS conference on epilepsy clinical trials offered several recommendations pertaining to seizure diaries for clinical research. These are listed below.
- 1.
Develop studies to validate current and new uses of epilepsy diaries as clinical and research tools.
- 2.
Develop a core of data sets useful for all epilepsy diary users, taking into account existing diaries and the NIH Common Data Element material.
- 3.
Develop a method to have core common diary information and
Disclosure of conflicts of interest
Dr. Fisher consults for Neuro-Vista, Cyberonics, ICVRx, Irody, SmartMonitor. Stanford University has received research support from Medtronic with Dr. Fisher as principle investigator. Dr. French serves as the president of The Epilepsy Study Consortium, a non-profit organization. NYU receives a fixed amount from the Epilepsy Study Consortium towards Dr. French’s salary. The money is for work performed by Dr. French on behalf of The Epilepsy Study Consortium, for consulting and clinical trial
Acknowledgments
Funding for the April 30, 2011 workshop, from which this manuscript emerged, was provided by the NINDS and the Epilepsy Study Consortium. The first author (RSF) is supported by the Maslah Saul MD Chair, the James and Carrie Anderson Fund for Epilepsy Research and the Susan E. Horngren Fund. We gratefully acknowledge Eyal Bartfeld of Irody, Inc. for a helpful review and critique.
References (39)
- et al.
Detecting nocturnal convulsions: efficacy of the MP5 monitor
Seizure
(2009) - et al.
Accidents at work among people with epilepsy. Results of a European prospective cohort study
Seizure
(2006) - et al.
Despite technical problems personal digital assistants outperform pen and paper when collecting patient diary data
J Clin Epidemiol
(2007) - et al.
Seizure prediction and recall
Epilepsy Behav
(2010) - et al.
The diagnostic utility of the ictal cry
Epilepsy Behav
(2010) - et al.
Electronic pain diary: a randomized crossover study
J Pain Symptom Manage
(2004) Automatic recognition of epileptic seizures in the EEG
Electroencephalogr Clin Neurophysiol
(1982)- et al.
Early follow-up data from seizure diaries can be used to predict subsequent seizures in same cohort by borrowing strength across participants
Epilepsy Behav
(2009) - et al.
When do patients forget their seizures? An electroclinical study
Epilepsy Behav
(2006) - et al.
An online diary for tracking epilepsy
Epilepsy Behav
(2011)