***TASK***
the task is to simplify the input abstract of a biomedical literature

***INPUT***
the input is the abstract of a biomedical literature

***OUTPUT***
the output is the simplified abstract for the input abstract of a biomedical literature

***DOCUMENTATION***

***EXAMPLES***

Input: We included nine industry-sponsored randomised controlled trials (3327 participants) in the review. Seven trials compared pregabalin to placebo. For the primary outcome, participants randomised to pregabalin were significantly more likely to attain a 50% or greater reduction in seizure frequency compared to placebo (RR 2.28, 95% CI 1.52 to 3.42, 7 trials, 2193 participants, low-certainty evidence). The odds of response doubled with an increase in dose from 300 mg/day to 600 mg/day (OR 1.99, 95% CI 1.74 to 2.28), indicating a dose-response relationship. Pregabalin was significantly associated with seizure freedom (RR 3.94, 95% CI 1.50 to 10.37, 4 trials, 1125 participants, moderate-certainty evidence). Participants were significantly more likely to withdraw from pregabalin treatment than placebo for any reason (RR 1.35, 95% CI 1.11 to 1.65, 7 trials, 2193 participants, moderate-certainty evidence) and for adverse effects (RR 2.65, 95% CI 1.88 to 3.74, 7 trials, 2193 participants, moderate-certainty evidence). Three trials compared pregabalin to three active-control drugs: lamotrigine, levetiracetam, and gabapentin. Participants allocated to pregabalin were significantly more likely to achieve a 50% or greater reduction in seizure frequency than those allocated to lamotrigine (RR 1.47, 95% CI 1.03 to 2.12, 1 trial, 293 participants) but not those allocated to levetiracetam (RR 0.94, 95% CI 0.80 to 1.11, 1 trial, 509 participants) or gabapentin (RR 0.96, 95% CI 0.82 to 1.12, 1 trial, 484 participants). We found no significant differences between pregabalin and lamotrigine (RR 1.39, 95% CI 0.40 to 4.83) for seizure freedom, however, significantly fewer participants achieved seizure freedom with add-on pregabalin compared to levetiracetam (RR 0.50, 95% CI 0.30 to 0.85). No data were reported for this outcome for pregabalin versus gabapentin. We found no significant differences between pregabalin and lamotrigine (RR 1.07, 95% CI 0.75 to 1.52), levetiracetam (RR 1.03, 95% CI 0.71 to 1.49), or gabapentin (RR 0.78, 95% CI 0.57 to 1.07) for treatment withdrawal due to any reason or due to adverse effects (pregabalin versus lamotrigine: RR 0.89, 95% CI 0.53 to 1.48; versus levetiracetam: RR 1.29, 95% CI 0.66 to 2.54; versus gabapentin: RR 1.07, 95% CI 0.54 to 2.11). Ataxia, dizziness, somnolence, weight gain, and fatigue were significantly associated with pregabalin. We rated the overall risk of bias in the included studies as low or unclear due to the possibility of publication bias and lack of methodological details provided. We rated the certainty of the evidence as very low to moderate using the GRADE approach. Pregabalin, when used as an add-on drug for treatment-resistant focal epilepsy, is significantly more effective than placebo at producing a 50% or greater seizure reduction and seizure freedom. Results demonstrated efficacy for doses from 150 mg/day to 600 mg/day, with increasing effectiveness at 600 mg doses, however issues with tolerability were noted at higher doses. The trials included in this review were of short duration, and longer-term trials are needed to inform clinical decision making.
Output:

This review examined data from 9 trials including a total of 3327 participants. Study participants were assigned using a random method to take pregabalin, placebo, or another antiepileptic drug in addition to their usual antiepileptic drugs. Participants taking pregabalin were more than twice as likely to have their seizure frequency reduced by 50% or more during a 12-week treatment period compared to those taking placebo, and were nearly four times more likely to be completely free of seizures. Pregabalin was shown to be effective across a range of doses (150 mg to 600 mg), with increasing effectiveness at higher doses. There was also an increased likelihood of treatment withdrawal with pregabalin. Side effects associated with pregabalin included ataxia, dizziness, fatigue, somnolence, and weight gain. When pregabalin was compared to three other antiepileptic drugs (lamotrigine, levetiracetam, and gabapentin), participants taking pregabalin were more likely to achieve a 50% reduction in seizure frequency than those taking lamotrigine. We found no significant differences between pregabalin and levetiracetam or gabapentin as add-on drugs. We rated all included studies as at low or unclear in risk of bias due to missing information about the methods used to conduct the trial and a suspicion of publication bias. Publication bias can occur when studies that report non-significant findings are not published. We suspected publication bias because the majority of included studies showed significant findings and were sponsored by the same drug company. We assessed the certainty of the evidence for the primary outcome of reduction in seizure frequency as low, meaning that we cannot be certain that the finding reported is accurate. However, we rated the certainty of the evidence for the outcomes seizure freedom and treatment withdrawal as moderate, so we can be fairly confident that these results are accurate. There were no data regarding the longer-term effectiveness of pregabalin, which should be investigated in future studies. The evidence is current to 5 July 2018.