Jennifer Weston

Assessment of the quality of harms reporting in non-randomised studies and randomised controlled studies of topiramate for the treatment of epilepsy using CONSORT criteria

PURPOSE Treatment decisions should be informed by high quality evidence of both the potential benefit and harms of treatment alternatives. Randomised controlled trials (RCTs) provide the best evidence regarding benefits; however information relating to serious, rare and long-term harms is usually available only from non-randomised studies (NRSs). The aim of this study was to use a checklist based on the CONSORT (Consolidating Standards for Reporting Trials) extension for harms recommendations to assess the quality of reporting of harms data in both NRSs and RCTs of antiepileptic drugs, using studies of topiramate as an example. RESULTS Seventy-eight studies were included from an online search of seven databases. Harms data was extracted from each study using a 25-point checklist. The mean number of items met was 11.5 (SD 2.96) per study. Commercially funded studies met on average 12.7 items and non-commercially funded studies met 10.08 (p value < 0.001). RCTs met on average 13.0 items and NRSs met 10.8 (p = 0.001). Multi-centre studies and commercially funded studies met significantly more items than single centre and non-commercially funded studies respectively. There was no significant difference in the mean number of items met by studies that had included adult vs. child participants, or studies published pre- vs. post-CONSORT extension for harms in 2004. CONCLUSIONS Reporting of harms is significantly better in RCTs than in NRSs of TPM, but is suboptimal overall and has not improved since the publication of CONSORT extension for harms in 2004. There is a need to improve the reporting of harms in order to better inform treatment decisions.

Antiepileptic drug monotherapy for epilepsy: a network meta-analysis

This is the protocol for a review and there is no abstract. The objectives are as follows: To review the time to withdrawal, remission and first seizure of 10 antiepileptic drugs (carbamazepine, phenytoin, valproate, phenobarbitone, oxcarbazepine, lamotrigine, gabapentin, topiramate, levetiracetam, zonisamide) currently used as monotherapy in children and adults with partial onset seizures or generalised tonic-clonic seizures with or without other generalised seizure types.

Maternal use of antiepileptic agents during pregnancy and major congenital malformations in children

Clinical Question Is maternal use of antiepileptic drugs during pregnancy associated with major congenital malformations in children? Bottom Line Certain antiepileptic drugs were associated with increased rates of congenital malformations (eg, spina bifida, cardiac anomalies). Lamotrigine (2.31% in 4195 pregnancies) and levetiracetam (1.77% in 817 pregnancies) were associated with the lowest risk and valproate was associated with the highest risk (10.93% in 2565 pregnancies) compared with the offspring of women without epilepsy (2.51% in 2154 pregnancies).

Feasibility study to examine discrepancy rates in prespecified and reported outcomes in articles submitted to The BMJ.

Objectives Adding, omitting or changing prespecified outcomes can result in bias because it increases the potential for unacknowledged or post hoc revisions of the planned analyses. Journals have adopted initiatives such as requiring the prospective registration of trials and the submission of study protocols to promote the transparency of reporting in clinical trials. The main objective of this feasibility study was to document the frequency and types of outcome discrepancy between prespecified outcomes in the protocol and reported outcomes in trials submitted to The BMJ. Methods A review of all 3156 articles submitted to The BMJ between 1 September 2013 and 30 June 2014. Trial registry entries, protocols and trial reports of randomised controlled trials published by The BMJ and a random sample of those rejected were reviewed. Editorial, peer reviewer comments and author responses were also examined to ascertain any reasons for discrepancies. Results In the study period, The BMJ received 311 trial manuscripts, 21 of which were subsequently published by the journal. In trials published by The BMJ, 27% (89/333) of the prespecified outcomes in the protocol were not reported in the submitted paper and 11% (31/275) of reported outcomes were not prespecified. In the sample of 21 trials rejected by The BMJ, 19% (63/335) of prespecified outcomes went unreported and 14% (45/317) of reported outcomes were not prespecified. None of the reasons provided by published authors were suggestive of outcome reporting bias as the reasons were unrelated to the results. Conclusions Mandating the prospective registration of a trial and requesting that a protocol be uploaded when submitting a trial article to a journal has the potential to promote transparency and safeguard the evidence base against outcome reporting biases as a result of outcome discrepancies. Further guidance is needed with regard to documenting reasons for outcome discrepancies.

Selective reporting in clinical trials - an examination of discrepancy rates in pre-specified and reported outcomes in articles submitted to the BMJ

Methods A review of all 3156 articles submitted to The BMJ between September 2013 and July 2014. Trial registry entries, protocols and trial reports of randomised controlled trials published by The BMJ and a random sample of those rejected were reviewed to determine the frequency and type of outcome discrepancies between pre-specified and reported outcomes. Editorial, peer reviewer comments and author responses were also examined to ascertain any reasons for discrepancies.