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Biomedical subjects

Jacqueline French

Publications and source records attributed to Jacqueline French.

8 recordsLinked to original sources
PubMed2006

Historical control withdrawal to monotherapy.

The design of clinical trials can be explained in terms of selection of a control group. Two options have included (a) using an active comparator, usually a standard drug such as carbamazepine (active control) or (b) using a placebo or low-dose control. Because neither active control nor placebo/dose control appeared to be acceptable alternatives for monotherapy studies in epilepsy, a new concept has been considered: the use of "historical control". This method uses the "expected" (imputed) behavior of placebo, based on prior trials. Some trials have been performed in patients with refractory epilepsy, who are withdrawn from their previous antiepileptic drugs, and converted to monotherapy on a study drug, using a low-dose comparator, frequently called "pseudo-placebo." A meta-analysis of all pseudo-placebo arms was performed to determine whether they could serve as a historical control for future monotherapy trials. The estimate of the combined percent exit was 86.1% (CI 78.6% to 93.6%). These data may be able to serve as a historical control for future monotherapy studies, obviating the need for a placebo/pseudo placebo arm.

Anticonvulsants↗
PubMed2006

Antiepileptic drugs in development.

BACKGROUND: Despite the success of several new antiepileptic drugs, about one third of patients with epilepsy are not seizure free on medication. Improvement in this situation might lie in drugs that are currently in development. RECENT DEVELOPMENTS: Some new antiepileptic drugs are modifications of those already available, referred to in this Rapid Review as evolutionary drugs. These modifications of existing drugs are developed to improve effectiveness, often by increasing tolerability. Other drugs work by new mechanisms and are usually discovered through screening of animal models. WHERE NEXT? The large number of drugs currently in clinical trials provides a measure of hope for patients whose epilepsy is not controlled with currently available medication. In the future, this range of antiepileptic drugs will probably increase because of the use of new animal models, discovery of new basic mechanisms of epileptogenesis, acceleration of proof of principle studies in people, and development of new methods of drug delivery.

Animals↗
PubMed2005

Rapid onset of action of levetiracetam in refractory epilepsy patients.

PURPOSE: To investigate whether rapid achievement of levetiracetam (LEV) steady state is translated into an immediate measurable efficacy. The time to onset of action of LEV immediately after its initiation in adult patients with refractory partial seizures was analyzed. METHODS: Treatment effect was assessed in a pooled analysis (n=883) from three randomized, double-blind, placebo-controlled add-on trials. RESULTS: The increase in the proportion of seizure-free patients over baseline was 15, 17, and 17% for the first, second, and third day, respectively, for the LEV 1,000-mg group (all differences statistically significant; McNemar p value<0.001), whereas the increase was 7, 9, and 9% for the 333-mg LEV group (differences not significant). No major changes were observed for the placebo group. For differences in proportion of seizure-free patients between groups, the probability of being seizure free in the LEV groups was twofold higher than in the placebo group. For the 1,000-mg LEV group, odds ratios were 2.3, 2.5, and 2.7 for the first, second, and third day of therapy, respectively; all differences versus placebo were statistically significant (logistic regression p values, all <0.001). The addition of LEV significantly increased the proportion of patients without a seizure as of the first day of therapy. Each of the first 3 days, seizure freedom was twice as likely to occur with LEV 1,000 mg than with placebo. CONCLUSIONS: Evidence of a rapid onset of action of LEV 1,000 mg was demonstrated through a significant increase in the proportion of seizure-free patients as of the first day of therapy.

Adolescent↗
PubMed2005

Fast and sustained efficacy of levetiracetam during titration and the first 3 months of treatment in refractory epilepsy.

PURPOSE: To investigate whether the efficacy of levetiracetam (LEV) is sustained in adult patients with refractory partial seizures over a 3-month period. METHODS: Treatment effect was assessed in a post hoc analysis by determining the proportion of seizure-free days during each week of a 3-month period after the initiation of treatment. Pooled data from three randomized, double-blind, placebo-controlled trials (n = 883) were analyzed. RESULTS: The mean proportion of seizure-free days was greater in the LEV group than in the placebo group. The difference, which was statistically significant, was observed as early as the first week after the initiation of treatment. It was higher in the first week of treatment and subsequently was maintained for each week over the 3-month period (p < 0.001 or p = 0.002 at each time point). Patients in the LEV group had on average 74% to 81% days each week without any seizure, compared with 69% to 72% in the placebo group. CONCLUSIONS: LEV is efficient in controlling seizures from the first week of drug initiation, during uptitration, and throughout the first 3 months of treatment. An interesting amplification of efficacy occurs in the first week of therapy, which is intriguing and warrants further investigation.

Adult↗
PubMed2003

Practice parameter: temporal lobe and localized neocortical resections for epilepsy.

PURPOSE: To examine evidence for effectiveness of anteromesial temporal lobe and localized neocortical resections for disabling complex partial seizures. METHODS: Systemic review and analysis of the literature since 1990. RESULTS: One intention-to-treat Class I randomized controlled trial of surgery for mesial temporal lobe epilepsy found that 58% of patients randomized to be evaluated for surgical therapy (64% of those who received surgery) were free of disabling seizures and 10 to 15% were unimproved at the end of 1 year, compared with 8% free of disabling seizures in the group randomized to continued medical therapy. There was a significant improvement in quantitative quality-of-life scores and a trend toward better social function at the end of 1 year for patients in the surgical group, no surgical mortality, and infrequent morbidity. Twenty-four Class IV series of temporal lobe resections yielded essentially identical results. There are similar Class IV results for localized neocortical resections; no Class I or II studies are available. CONCLUSIONS: A single Class I study and 24 Class IV studies indicate that the benefits of anteromesial temporal lobe resection for disabling complex partial seizures is greater than continued treatment with antiepileptic drugs, and the risks are at least comparable. For patients who are compromised by such seizures, referral to an epilepsy surgery center should be strongly considered. Further studies are needed to determine if neocortical seizures benefit from surgery, and whether early surgical intervention should be the treatment of choice for certain surgically remediable epileptic syndromes.

Anticonvulsants↗