There is no evidence for a difference in antiepileptic efficacy between phenobarbital and any other compared AED , yet no evidence for absolute efficacy .
No convincing evidence exists for an excess of behavioural adverse effects , over other AEDs , attributable to phenobarbital .
Masked studies of phenobarbital in childhood epilepsy have shown no significant differences in behavioural or cognitive adverse effects compared to other AEDs .
This is in contrast to the excess of such adverse effects reported in studies open to observer bias .
However , the one finding of reduction in cognitive ability associated with phenobarbital treatment for febrile convulsions remains a concern .
INTRODUCTION : Against a background of concern about the safety of new pharmaceutical products , there has been renewed interest in one of the oldest antiepileptic drugs ( AEDs ) , phenobarbital .
Although still in widespread use in developing countries , its popularity has slipped in Western countries over the past century , partly because of controversy about its adverse effect profile .
This critical review examines the evidence supporting its effectiveness and its associated behavioural adverse effects for febrile convulsions and childhood epilepsy .
Analysis of clinical trials by treatment actually received: is it really an option?
The primary analysis of a r and omized clinical trial should compare patients in their r and omly assigned treatment groups ( intention to treat analysis ) . When a substantial number of subjects fail to take a prescribed medication or are switched to a different study medication , it is tempting to consider treatment comparisons using only those subjects with treatment as actually received rather than as prescribed . There are several arguments against this approach : the prognostic balance brought about by r and omization is likely to be disturbed ; sample size will be reduced ; and the validity of the statistical test procedures will be undermined . Further , results of analysis by treatment actually received may suffer from a bias introduced by using compliance , a factor often related to outcome independently of the treatment received , to determine the groups for comparison . The extent and nature of this bias will be related to the definition of compliance in an as treated analysis , a definition which could be unintentionally self-serving . We have investigated the problem of the definition of actual treatment in the context of a recent clinical trial . We used several definitions to classify patients as  having received or not received treatment as prescribed .  These definitions , when used in as treated analyses , provided results that were at times inconsistent or counter-intuitive , and which neither helped to confirm nor further explain the intention to treat analysis
There is no evidence for a difference in antiepileptic efficacy between phenobarbital and any other compared AED , yet no evidence for absolute efficacy .
No convincing evidence exists for an excess of behavioural adverse effects , over other AEDs , attributable to phenobarbital .
Masked studies of phenobarbital in childhood epilepsy have shown no significant differences in behavioural or cognitive adverse effects compared to other AEDs .
This is in contrast to the excess of such adverse effects reported in studies open to observer bias .
However , the one finding of reduction in cognitive ability associated with phenobarbital treatment for febrile convulsions remains a concern .
INTRODUCTION : Against a background of concern about the safety of new pharmaceutical products , there has been renewed interest in one of the oldest antiepileptic drugs ( AEDs ) , phenobarbital .
Although still in widespread use in developing countries , its popularity has slipped in Western countries over the past century , partly because of controversy about its adverse effect profile .
This critical review examines the evidence supporting its effectiveness and its associated behavioural adverse effects for febrile convulsions and childhood epilepsy .