Assessment of Pregabalin Postapproval Trials and the Suggestion of Efficacy for New Indications

Federico, Carole A; Wang, Taiji; Doussau, A.; Mogil, Jeffrey S.; Fergusson, Dean; Kimmelman, Jonathan

doi:10.1001/jamainternmed.2018.5705

Cited by 26 publications

(33 citation statements)

References 45 publications

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“…[1][2][3][4][5] Over the last decade, the off-label use of gabapentinoids for the control of acute nociceptive or neuropathic pain has drastically increased in several countries, [6][7][8] and they are now routinely used for the management of postoperative analgesia to decrease pain and opioid use. [9][10][11][12][13][14] However, scientific data supporting the increased use are divergent, which may reflect clinical agnosticism rather than new evidence of clinical effectiveness. [15][16][17][18][19][20][21]…”

Section: What This Article Tells Us That Is Newmentioning

confidence: 99%

Perioperative Use of Gabapentinoids for the Management of Postoperative Acute Pain

Verret¹,

Lauzier²,

Zarychanski³

et al. 2020

Anesthesiology

301

193

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Background Widely used for acute pain management, the clinical benefit from perioperative use of gabapentinoids is uncertain. The aim of this systematic review was to assess the analgesic effect and adverse events with the perioperative use of gabapentinoids in adult patients. Methods Randomized controlled trials studying the use of gabapentinoids in adult patients undergoing surgery were included. The primary outcome was the intensity of postoperative acute pain. Secondary outcomes included the intensity of postoperative subacute pain, incidence of postoperative chronic pain, cumulative opioid use, persistent opioid use, lengths of stay, and adverse events. The clinical significance of the summary estimates was assessed based on established thresholds for minimally important differences. Results In total, 281 trials (N = 24,682 participants) were included in this meta-analysis. Compared with controls, gabapentinoids were associated with a lower postoperative pain intensity (100-point scale) at 6 h (mean difference, −10; 95% CI, −12 to −9), 12 h (mean difference, −9; 95% CI, −10 to −7), 24 h (mean difference, −7; 95% CI, −8 to −6), and 48 h (mean difference, −3; 95% CI, −5 to −1). This effect was not clinically significant ranging below the minimally important difference (10 points out of 100) for each time point. These results were consistent regardless of the type of drug (gabapentin or pregabalin). No effect was observed on pain intensity at 72 h, subacute and chronic pain. The use of gabapentinoids was associated with a lower risk of postoperative nausea and vomiting but with more dizziness and visual disturbance. Conclusions No clinically significant analgesic effect for the perioperative use of gabapentinoids was observed. There was also no effect on the prevention of postoperative chronic pain and a greater risk of adverse events. These results do not support the routine use of pregabalin or gabapentin for the management of postoperative pain in adult patients. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

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Section: What This Article Tells Us That Is Newmentioning

confidence: 99%

Perioperative Use of Gabapentinoids for the Management of Postoperative Acute Pain

Verret¹,

Lauzier²,

Zarychanski³

et al. 2020

Anesthesiology

301

193

View full text Add to dashboard Cite

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“…It is registered in Australia for the treatment of neuropathic pain and seizures, while it is also approved for generalised anxiety disorder in Europe and fibromyalgia in the United States (US). (1) In recent years, its use has increased markedly in North America, Europe, and the United Kingdom (UK) (2)(3)(4). In Australia, pregabalin dispensing nearly tripled in the first four years since it started to be subsidised in March 2013 by the Pharmaceutical Benefits Scheme (PBS), the national program that provides access to approved medicines.…”

Section: Introductionmentioning

confidence: 99%

Pregabalin prescribing patterns in Australian general practice, 2012–2018: a cross-sectional study

Schaffer

Busingye²,

Chidwick

et al. 2020

BJGP Open

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BackgroundIn 2013 pregabalin was subsidised by Australia’s Pharmaceutical Benefits Scheme (PBS) for neuropathic pain. Since the subsidy, pregabalin prescribing has been increasing in Australia and so has related harm. There are concerns it is being prescribed for indications other than neuropathic pain, which have little evidence of efficacy.AimTo describe pregabalin prescribing in Australian general practice.Design & settingA cross-sectional study of patients attending 445 general practice sites in the national MedicineInsight database from March 2012–February 2018.MethodThe following aspects were calculated: the proportion of prescriptions that were for pregabalin per year; the prevalence of pain conditions in patients prescribed pregabalin; and same-day prescribing of pregabalin with opioids or benzodiazepines.ResultsPrescribing increased from 13 per 10 000 to 104 per 10 000 prescriptions between 2012–2013 and 2017–2018. A total of 1 891 623 patients were identified of whom 114 123 (6.0%) were prescribed pregabalin; 49.7% (n = 56 772) had a recorded diagnosis of neuropathic pain. Among people prescribed pregabalin without a recorded diagnosis of neuropathic pain, 43.5% (n = 24 927) had a diagnosis of back problems, 8.8% (n = 5073) chronic pain, and 26.4% (n = 30 146) had no pain diagnosis. Pregabalin was prescribed the same day as an opioid to 38.1% of patients (95% confidence interval [CI] = 37.1% to 39.1%) and a benzodiazepine to 13.1% of patients (95% CI = 12.5% to 13.7%). Patients with a diagnosis of chronic pain had the highest rate of same-day prescribing of pregabalin with an opioid (70.4%, 95% CI = 68.9% to 71.9%) or a benzodiazepine (25.8%, 95% CI = 24.2% to 27.4%)ConclusionSubstantial increases in pregabalin prescribing were identified in Australian general practice, but only half of patients had a neuropathic pain diagnosis recorded, the only approved indication for subsidy. High rates of same-day prescribing with opioids and benzodiazepines may put patients at increased risk of harm.

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“…31 Evidence to date suggests that valid data confirming the clinical benefits of drugs and devices on the basis of patient-centred and clinically-relevant outcomes may not routinely emerge in the post-marketing period. 37 According to a recent study, only one-fifth of required post-marketing studies of cancer drug indications approved via the FDA's accelerated approval pathway over the past quarter century demonstrated improvements in overall survival in randomised controlled trials, though patients may occasionally derive quality of life benefits in some limited cases without a survival gain. 38…”

Section: Industry-initiated Research In the Post-marketing Periodmentioning

confidence: 99%

Generating comparative evidence on new drugs and devices after approval

et al. 2020

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Certain limitations of evidence available on drugs and devices at the time of market approval often persist in the post-marketing period. Too often, post-marketing research landscape is fragmented. When regulatory agencies require pharmaceutical and device manufacturers to conduct studies in the post-marketing period, these studies may remain incomplete many years after approval. Even when completed, many post-marketing studies lack meaningful active comparators, have observational designs, and may not collect patient-relevant outcomes. It is crucial for regulators, in collaboration with the industry and patients, to ensure that the important questions that are unanswered at the time of drug and device approval are resolved in a timely fashion during the post-marketing phase. We propose a set of seven key guiding principles that we believe will provide the necessary incentives for pharmaceutical and device manufacturers to generate comparative data in the post-marketing period. First, regulators and pharmaceutical companies (for drugs), notified bodies and manufacturers (for devices) should develop customised evidence generation plans, ensuring that future post-approval studies address any limitations of the data available at the time of market entry that would influence the benefit-risk profiles of drugs and devices. Second, post-marketing studies should be designed hierarchically: priority should be given to efforts aimed at evaluating a product's net clinical benefit in randomised trials compared with current known effective therapy, whenever possible, to address common decisional dilemmas. Third, post-marketing studies should incorporate active comparators as appropriate. Fourth, use of non-randomised studies for the evaluation of clinical benefit in the post-marketing period should be limited to instances when the magnitude of effect is deemed to be very large or when it is possible to reasonably infer the comparative benefits or risks in settings where doing a randomised trial is not feasible. Fifth, efficiency of randomised trials should be improved by streamlining patient recruitment and data collection through innovative design elements. Sixth, governments should directly support and facilitate the production of comparative post-marketing data by investing in the development of collaborative research networks and data systems that reduce the complexity, cost, and waste of rigorous postmarketing research efforts. Seventh, financial incentives and penalties should be developed or more actively reinforced.

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Assessment of Pregabalin Postapproval Trials and the Suggestion of Efficacy for New Indications

Cited by 26 publications

References 45 publications

Perioperative Use of Gabapentinoids for the Management of Postoperative Acute Pain

Perioperative Use of Gabapentinoids for the Management of Postoperative Acute Pain

Pregabalin prescribing patterns in Australian general practice, 2012–2018: a cross-sectional study

Generating comparative evidence on new drugs and devices after approval

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