Clinical trial outcome in neuropathic pain

Katz, Jennifer; Finnerup, Nanna Brix; Dworkin, Robert H.

doi:10.1212/01.wnl.0000275528.01263.6c

Cited by 159 publications

(126 citation statements)

References 40 publications

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“…In general, crossover studies have lower placebo responses than parallel group trials. 36 Interestingly, previous studies in SCI pain have found low 8 or no 9,34 overall placebo response, but the reason for this is unknown. Central nervous system-related side effects are common with most anticonvulsants, although the newer generation anticonvulsants, such as levetiracetam, generally have better safety profiles and more favorable pharmacokinetic profiles than older generation anticonvulsants.…”

Section: Discussionmentioning

confidence: 98%

Levetiracetam in spinal cord injury pain: a randomized controlled trial

et al. 2009

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Study design: A randomized, double-blind, placebo-controlled, crossover, multicenter trial. A 1-week baseline period was followed by two treatment periods of 5 weeks duration with levetiracetam increased from 500 mg b.i.d. to a maximum of 1500 mg b.i.d. separated by a 1-week washout period. Objectives: The objective of the study was primarily to evaluate the efficacy of the anticonvulsant levetiracetam in patients with spinal cord injury (SCI) at-and below-level pain and secondarily to evaluate the effect on spasm severity. Setting: Outpatients at two spinal cord units and a pain center. Methods: Patients were allowed to continue their usual pain treatment at a constant dose. The primary outcome measure was the change in median daily pain score (on a 0-10 point numeric rating scale) from 1-week baseline period to the last week of each treatment period. Secondary outcome measures included pain relief of at-and below-level pain, allodynia, spasms and spasticity. Results: A total of 36 patients with SCI at-and or below-level pain were enrolled. Of these, 24 patients completed the trial. We found no effect of levetiracetam on the primary (P ¼ 0.46) or any of the secondary outcome measures. Only two patients continued levetiracetam treatment following the trial, and one patient was still in levetiracetam treatment at the 6-month follow-up. Levetiracetam was generally well tolerated with no serious adverse events. Conclusions: Levetiracetam does not relieve neuropathic pain or spasm severity following spinal cord injury.

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Section: Discussionmentioning

confidence: 98%

Levetiracetam in spinal cord injury pain: a randomized controlled trial

et al. 2009

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“…Or is it possible that specific characteristics of the study population, the selected patient group, or the defined primary outcome have obscured a positive response? 8 These observations have raised the question of whether an entirely different strategy, in which pain is analyzed on the basis of underlying mechanisms, could 3,9 have emphasized the rationale for a treatment approach directed at one or more mechanisms rather than at diseases because new treatments are being developed on the basis of the biological mechanisms that underlie pain. One area that needs such a new approach is neuropathic pain.…”

Section: Rationale For a New Classificationmentioning

confidence: 99%

Evaluation of Symptom Heterogeneity in Neuropathic Pain Using Assessments of Sensory Functions

Arning

Baron

2009

Neurotherapeutics

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Summary:Classification of neuropathic pain has been based on disease entities, anatomical localization, or histological observations. Over the past decade, there has been an explosion in our understanding of the basic mechanisms of neuropathic pain. The exciting advances in basic science are paralleled by the recognition from clinical investigations that neuropathic pain is not a monolithic entity, but instead presents as a composite of pain and other sensory symptoms. Attempts are under way to supplement the traditional classification with a classification that links pain and sensory symptoms with neurobiological mechanisms. This mechanism-or symptom-based classification takes both negative and positive sensory symptoms into account. By using a battery of several standardized quantitative sensory tests, the characteristic profile of sensory symptoms can be elucidated in each patient. Moreover, in questionnaires the verbal descriptors can depict the quality and intensity of the individual pain. The approach of classifying and subgrouping patients with neuropathic pain on the basis of symptoms or signs opens up new possibilities for stratifying patients in clinical trials. First, in clinical proof-of-concept trials the study population can be enriched prospectively on the basis of entry criteria defined a priori. This enrichment with patients who potentially require a specific treatment should increase the likelihood for positive trial outcomes. Second, in clinical practice it becomes possible to establish an individualized therapy-that is, to identify the particular patients who require a specific treatment option.

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“…RCTs, however, have their limitations and some recent RCTs in neuropathic pain, including in PHN, showed only moderate treatment effects or even failed [12,16,26]. Therefore, there is a growing concern about the quality of RCTs, and their inability to detect a positive signal in an efficacious analgesic [27].…”

Section: Discussionmentioning

confidence: 99%

“…It has also become clear that since RCTs are designed to test a therapeutic hypothesis under an optimal setting, several factors may comprise their strict and controlled conditions and thus restrict their application to real-world clinical practice [11]. For example, certain study characteristics (such as larger sample size or parallel-study groups) may be important for decreasing placebo response rates in RCTs and thus increasing the likelihood of positive outcomes [12]. Likewise, strict population inclusion and exclusion criteria in RCTs may result in the elimination of important segments of the population, narrowing the relevance of the treatment [10].…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, such studies can be an important complement to RCTs, and comparing the conclusions of RCTs and real-world studies can improve interpretation of each other's results. For example, some recent RCTs in PHN and other neuropathic pain syndromes were characterized by high placebo rates and thus showed diminished or no drug efficacy over placebo [12,16]. Comparisons between medical evidence established in RCTs and real-world studies could help evaluate possible factors associated with positive vs. negative treatment outcomes and guide better design of future neuropathic pain trials.…”

Section: Introductionmentioning

confidence: 99%

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