There are several ethical, regulatory, and logistical challenges to conducting long-term placebo-controlled, double-blind randomized controlled trials (RCTs). Because of this, the majority of contemporary phase III trials on opioid efficacy and safety do not last longer than three months.
In light of this, open-label studies are particularly valuable, as they are often of longer duration and “reflect patient experience before and after long-term opioid therapy,” according to the authors of a poster presented at the American Pain Society’s 32nd Annual Scientific Meeting, held May 8-13, 2013, in New Orleans, LA.
In “Long-term Efficacy and Safety of Opioid Therapy for Chronic Non-cancer Pain: Evidence from Randomized and Open-label Studies,” Matsuno, Wallace, Glanzman, et al, analyzed data from published RCTs and open-label studies that had a duration of six months or longer to learn more about the long-term efficacy and safety of opioid therapy for patients with chronic non-cancer pain.
They conducted a literature search of major databases to identify RCTs, single-arm open-label trials, and open-label extension studies following an RCT that were six months or more in duration. They also searched clinical guidelines, consensus statements, and other sources to identify additional articles.
They identified two RCTs and 40 open label studies (28 single-arm and 12 extension studies) that met their search criteria. In studies that evaluated opioid efficacy using the Brief Pain Inventory, Visual Analog Scale, or Numeric Rating Scale, the authors of the current study determined “percent change in average, usual, or current pain from baseline of study to end of study.”
In studies that reported effect on functional status in patients on opioid therapy using the 36-item Short Form Health Survey or the 12-item Short Form Health Survey, the authors determined “percent change in mental and/or physical component scores from baseline of study to end of study.”
The studies were rated as “positive” if pain scores and/or function improved in an RCT or single-arm open-label study, or were maintained in an open-label extension study following an RCT. A study was rated “negative” if pain scores and/or function declined or were not maintained. Studies in which there was no change in scores or status were labeled “neutral.”
Most of the studies on analgesic efficacy were rated “positive” (90% of all studies). Both RCTs showed improvement in pain scores of at least 25%. A large majority of single-arm open-label studies (88%) also showed at least a 25% improvement in pain scores.
Two studies showed an improvement of 25% or more in mental function (although mental health was either unchanged or somewhat improved in most studies). Effects on physical function were more of a mixed bag, with some studies showing a 25% or greater decline in health scores, while others showed a 35% or greater improvement. Adverse events (AEs) were common in all studies, but were mild moderate in intensity. The most commonly reported AEs were nausea, vomiting, constipation, and somnolence.
The authors identified several limitations with the current study, including a wide variation in patient populations across studies (differentiating factors included type and severity of pain condition, and patients’ prior opioid experiences). The quality of the studies was also not evaluated.
Based on these results, the authors concluded that “the body of literature for clinical studies supports the long-term efficacy of opioid analgesic therapy,” with a subset of these studies “suggesting that long-term opioid analgesic therapy may also improve functional status” in patients.