The Safety of Medications used to Treat Peripheral Neuropathic Pain, Part 2 (Opioids, Cannabinoids and Other Drugs): review of Double-Blind, Placebo-Controlled, Randomized Clinical Trials

References

• Finnerup NB, Attal N, Haroutounian S, et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol. 2015;14:162–173.
   PubMed Web of Science ®Google Scholar
• Hershman DL, Lacchetti C, Dworkin RH, et al. Prevention and management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2014;32:1941–1967.
   PubMed Web of Science ®Google Scholar
• Selvy M, Cuménal M, Kerckhove N, et al. The safety of medications used to treat peripheral neuropathic pain, part 1 (antidepressants and antiepileptics): review of double-blind, placebo-controlled, randomized clinical trials. Expert Opin Drug Saf. 2020;19:707–733.
   Web of Science ®Google Scholar
• Brownstein MJ. A brief history of opiates, opioid peptides, and opioid receptors. Proc Natl Acad Sci USA. 1993;90:5391–5393.
   PubMed Web of Science ®Google Scholar
• Rosenblum A, Marsch LA, Joseph H, et al. Opioids and the treatment of chronic pain: controversies, current status, and future directions. Exp Clin Psychopharmacol. 2008;16:405–416.
   PubMed Web of Science ®Google Scholar
• Manchikanti L, Helm S, Fellows B, et al. Opioid epidemic in the United States. Pain Physician. 2012;15:ES9–38.
   PubMed Web of Science ®Google Scholar
• Gallagher H, Galvin D. Opioids for chronic non-cancer pain. BJA Educ. 2018;18:337–341.
   PubMed Web of Science ®Google Scholar
• Häuser W, Schug S, Furlan AD. The opioid epidemic and national guidelines for opioid therapy for chronic noncancer pain: a perspective from different continents. Pain Rep. 2017;2:e599.
   PubMedGoogle Scholar
• Kissin I. Long-term opioid treatment of chronic nonmalignant pain: unproven efficacy and neglected safety? J Pain Res. 2013;6:513–529.
   PubMed Web of Science ®Google Scholar
• Okie S. A flood of opioids, a rising tide of deaths. N Engl J Med. 2010;363:1981–1985.
   PubMed Web of Science ®Google Scholar
• Franklin GM; American Academy of Neurology. Opioids for chronic noncancer pain: a position paper of the American Academy of Neurology. Neurology. 2014;83:1277–1284.
   PubMed Web of Science ®Google Scholar
• Dowell D, Haegerich TM, Chou R. CDC guideline for prescribing opioids for chronic pain–United States, 2016. JAMA. 2016;315:1624–1645.
   PubMed Web of Science ®Google Scholar
• Gilron I, Baron R, Jensen T. Neuropathic pain: principles of diagnosis and treatment. Mayo Clin Proc. 2015;90:532–545.
   PubMed Web of Science ®Google Scholar
• McNicol ED, Midbari A, Eisenberg E. Opioids for neuropathic pain. Cochrane Database Syst Rev. 2013;(8):CD006146.
   PubMedGoogle Scholar
• Schwartz S, Etropolski M, Shapiro DY, et al. Safety and efficacy of tapentadol ER in patients with painful diabetic peripheral neuropathy: results of a randomized-withdrawal, placebo-controlled trial. Curr Med Res Opin. 2011;27:151–162.
   PubMed Web of Science ®Google Scholar
• Vinik AI, Shapiro DY, Rauschkolb C, et al. A randomized withdrawal, placebo-controlled study evaluating the efficacy and tolerability of tapentadol extended release in patients with chronic painful diabetic peripheral neuropathy. Diabetes Care. 2014;37:2302–2309.
   PubMed Web of Science ®Google Scholar
• Niesters M, Proto PL, Aarts L, et al. Tapentadol potentiates descending pain inhibition in chronic pain patients with diabetic polyneuropathy. Br J Anaesth. 2014;113(1):148–156. .
   PubMed Web of Science ®Google Scholar
• Tominaga Y, Koga H, Uchida N, et al. Methodological issues in conducting pilot trials in chronic pain as randomized, double-blind, placebo-controlled studies. Drug Res (Stuttg). 2016;66:363–370.
   PubMed Web of Science ®Google Scholar
• Simpson DM, Messina J, Xie F, et al. Fentanyl buccal tablet for the relief of breakthrough pain in opioid-tolerant adult patients with chronic neuropathic pain: a multicenter, randomized, double-blind, placebo-controlled study. Clin Ther. 2007;29:588–601.
   PubMed Web of Science ®Google Scholar
• Jensen MP, Friedman M, Bonzo D, et al. The validity of the neuropathic pain scale for assessing diabetic neuropathic pain in a clinical trial. Clin J Pain. 2006;22:97–103.
   PubMed Web of Science ®Google Scholar
• Gimbel JS, Richards P, Portenoy RK. Controlled-release oxycodone for pain in diabetic neuropathy: a randomized controlled trial. Neurology. 2003;60:927–934.
   PubMed Web of Science ®Google Scholar
• Sindrup SH, Konder R, Lehmann R, et al. Randomized controlled trial of the combined monoaminergic and opioid investigational compound GRT9906 in painful polyneuropathy. Eur J Pain. 2012;16:849–859.
   PubMed Web of Science ®Google Scholar
• Arbaiza D, Vidal O. Tramadol in the treatment of neuropathic cancer pain: a double-blind, placebo-controlled study. Clin Drug Investig. 2007;27:75–83.
   PubMed Web of Science ®Google Scholar
• Simpson RW, Wlodarczyk JH. Transdermal buprenorphine relieves neuropathic pain: a randomized, double-blind, parallel-group, placebo-controlled trial in diabetic peripheral neuropathic pain. Diabetes Care. 2016;39:1493–1500.
   PubMed Web of Science ®Google Scholar
• Harrison T, Miyahara S, Lee A, et al. Experience and challenges presented by a multicenter crossover study of combination analgesic therapy for the treatment of painful HIV-associated polyneuropathies. Pain Med. 2013;14:1039–1047.
   PubMed Web of Science ®Google Scholar
• Morley JS, Bridson J, Nash TP, et al. Low-dose methadone has an analgesic effect in neuropathic pain: a double-blind randomized controlled crossover trial. Palliat Med. 2003;17:576–587.
   PubMed Web of Science ®Google Scholar
• Harke H, Gretenkort P, Ladleif HU, et al. The response of neuropathic pain and pain in complex regional pain syndrome I to carbamazepine and sustained-release morphine in patients pretreated with spinal cord stimulation: a double-blinded randomized study. Anesth Analg. 2001;92:488–495.
   PubMed Web of Science ®Google Scholar
• Lambert DM, Fowler CJ. The endocannabinoid system: drug targets, lead compounds, and potential therapeutic applications. J Med Chem. 2005;48:5059–5087.
   PubMed Web of Science ®Google Scholar
• Elsohly MA, Gul W, Wanas AS, et al. Synthetic cannabinoids: analysis and metabolites. Life Sci. 2014;97:78–90.
   PubMed Web of Science ®Google Scholar
• Pacher P, Bátkai S, Kunos G. The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol Rev. 2006;58:389–462.
   PubMed Web of Science ®Google Scholar
• Serpell M, Ratcliffe S, Hovorka J, et al. A double-blind, randomized, placebo-controlled, parallel group study of THC/CBD spray in peripheral neuropathic pain treatment. Eur J Pain. 2014;18:999–1012.
   PubMed Web of Science ®Google Scholar
• Lynch ME, Cesar-Rittenberg P, Hohmann AG. A double-blind, placebo-controlled, crossover pilot trial with extension using an oral mucosal cannabinoid extract for treatment of chemotherapy-induced neuropathic pain. J Pain Symptom Manage. 2014;47:166–173.
   PubMed Web of Science ®Google Scholar
• Selvarajah D, Gandhi R, Emery CJ, et al. Randomized placebo-controlled double-blind clinical trial of cannabis-based medicinal product (Sativex) in painful diabetic neuropathy: depression is a major confounding factor. Diabetes Care. 2010;33:128–130.
   PubMed Web of Science ®Google Scholar
• Nurmikko TJ, Serpell MG, Hoggart B, et al. Sativex successfully treats neuropathic pain characterised by allodynia: a randomised, double-blind, placebo-controlled clinical trial. Pain. 2007;133:210–220.
   PubMed Web of Science ®Google Scholar
• Toth C, Mawani S, Brady S, et al. An enriched-enrolment, randomized withdrawal, flexible-dose, double-blind, placebo-controlled, parallel assignment efficacy study of nabilone as adjuvant in the treatment of diabetic peripheral neuropathic pain. Pain. 2012;153:2073–2082.
   PubMed Web of Science ®Google Scholar
• Ellis RJ, Toperoff W, Vaida F, et al. Smoked medicinal cannabis for neuropathic pain in HIV: a randomized, crossover clinical trial. Neuropsychopharmacology. 2009;34:672–680.
   PubMed Web of Science ®Google Scholar
• Abrams DI, Jay CA, Shade SB, et al. Cannabis in painful HIV-associated sensory neuropathy: a randomized placebo-controlled trial. Neurology. 2007;68:515–521.
   PubMed Web of Science ®Google Scholar
• Karst M, Salim K, Burstein S, et al. Analgesic effect of the synthetic cannabinoid CT-3 on chronic neuropathic pain: a randomized controlled trial. JAMA. 2003;290:1757–1762.
   PubMed Web of Science ®Google Scholar
• McCartney CJL, Sinha A, Katz J. A qualitative systematic review of the role of N-methyl-D-aspartate receptor antagonists in preventive analgesia. Anesth Analg. 2004;98:1385–1400.
   PubMed Web of Science ®Google Scholar
• Tena B, Gomar C, Rios J. Perioperative epidural or intravenous ketamine does not improve the effectiveness of thoracic epidural analgesia for acute and chronic pain after thoracotomy. Clin J Pain. 2014;30:490–500.
   PubMed Web of Science ®Google Scholar
• Dualé C, Sibaud F, Guastella V, et al. Perioperative ketamine does not prevent chronic pain after thoracotomy. Eur J Pain. 2009;13:497–505.
   PubMed Web of Science ®Google Scholar
• Mendola C, Cammarota G, Netto R, et al. S(+)-ketamine for control of perioperative pain and prevention of post thoracotomy pain syndrome: a randomized, double-blind study. Minerva Anestesiol. 2012;78:757–766.
   PubMed Web of Science ®Google Scholar
• Lynch ME, Clark AJ, Sawynok J, et al. Topical 2% amitriptyline and 1% ketamine in neuropathic pain syndromes: a randomized, double-blind, placebo-controlled trial. Anesthesiology. 2005;103:140–146.
   PubMed Web of Science ®Google Scholar
• Morel V, Joly D, Villatte C, et al. Memantine before mastectomy prevents post-surgery pain: a randomized, blinded clinical trial in surgical patients. PLoS ONE. 2016;11:e0152741.
   PubMed Web of Science ®Google Scholar
• Schifitto G, Yiannoutsos CT, Simpson DM, et al. A placebo-controlled study of memantine for the treatment of human immunodeficiency virus-associated sensory neuropathy. J Neurovirol. 2006;12:328–331.
   PubMed Web of Science ®Google Scholar
• Wiech K, Kiefer R-T, Töpfner S, et al. A placebo-controlled randomized crossover trial of the N-methyl-D-aspartic acid receptor antagonist, memantine, in patients with chronic phantom limb pain. Anesth Analg. 2004;98:408–413.
   PubMed Web of Science ®Google Scholar
• Nikolajsen L, Gottrup H, Kristensen AG, et al. Memantine (a N-methyl-D-aspartate receptor antagonist) in the treatment of neuropathic pain after amputation or surgery: a randomized, double-blinded, cross-over study. Anesth Analg. 2000;91:960–966.
   PubMed Web of Science ®Google Scholar
• Schmid RL, Sandler AN, Katz J. Use and efficacy of low-dose ketamine in the management of acute postoperative pain: a review of current techniques and outcomes. Pain. 1999;82:111–125.
   PubMed Web of Science ®Google Scholar
• Niesters M, Martini C, Dahan A. Ketamine for chronic pain: risks and benefits. Br J Clin Pharmacol. 2014;77:357–367.
   PubMed Web of Science ®Google Scholar
• Kurdi MS, Theerth KA, Deva RS. Ketamine: current applications in anesthesia, pain, and critical care. Anesth Essays Res. 2014;8:283–290.
   PubMedGoogle Scholar
• Kurian R, Raza K, Shanthanna H. A systematic review and meta-analysis of memantine for the prevention or treatment of chronic pain. Eur J Pain. 2019;23:1234–1250.
   PubMed Web of Science ®Google Scholar
• Anand P, Bley K. Topical capsaicin for pain management: therapeutic potential and mechanisms of action of the new high-concentration capsaicin 8% patch. Br J Anaesth. 2011;107:490–502.
   PubMed Web of Science ®Google Scholar
• Szallasi A, Blumberg PM. Vanilloid (Capsaicin) receptors and mechanisms. Pharmacol Rev. 1999;51:159–212.
   PubMed Web of Science ®Google Scholar
• Derry S, Moore RA. Topical capsaicin (low concentration) for chronic neuropathic pain in adults. Cochrane Database Syst Rev. 2012;(9):CD010111.
   PubMed Web of Science ®Google Scholar
• Derry S, Rice AS, Cole P, et al. Topical capsaicin (high concentration) for chronic neuropathic pain in adults. Cochrane Database Syst Rev. 2017;1:CD007393.
   PubMed Web of Science ®Google Scholar
• Kulkantrakorn K, Lorsuwansiri C, Meesawatsom P. 0.025% capsaicin gel for the treatment of painful diabetic neuropathy: a randomized, double-blind, crossover, placebo-controlled trial. Pain Pract. 2013;13:497–503.
   PubMed Web of Science ®Google Scholar
• Kulkantrakorn K, Chomjit A, Sithinamsuwan P, et al. 0.075% capsaicin lotion for the treatment of painful diabetic neuropathy: a randomized, double-blind, crossover, placebo-controlled trial. J Clin Neurosci. 2019;62:174–179.
   PubMed Web of Science ®Google Scholar
• Simpson DM, Robinson-Papp J, Van J, et al. Capsaicin 8% patch in painful diabetic peripheral neuropathy: a randomized, double-blind, placebo-controlled study. J Pain. 2017;18:42–53.
   PubMed Web of Science ®Google Scholar
• Moon J-Y, Lee P-B, Kim Y-C, et al. Efficacy and safety of 0.625% and 1.25% capsaicin patch in peripheral neuropathic pain: multi-center, randomized, and semi-double blind controlled study. Pain Physician. 2017;20:27–35.
   PubMed Web of Science ®Google Scholar
• Teixeira MJ, Menezes LMB, Silva V, et al. Liposomal topical capsaicin in post-herpetic neuralgia: a safety pilot study. Arq Neuropsiquiatr. 2015;73:237–240.
   PubMed Web of Science ®Google Scholar
• Campbell CM, Diamond E, Schmidt WK, et al. A randomized, double-blind, placebo-controlled trial of injected capsaicin for pain in Morton’s neuroma. Pain. 2016;157:1297–1304.
   PubMed Web of Science ®Google Scholar
• Paice JA, Ferrans CE, Lashley FR, et al. Topical capsaicin in the management of HIV-associated peripheral neuropathy. J Pain Symptom Manage. 2000;19:45–52.
   PubMed Web of Science ®Google Scholar
• Frias B, Merighi A. Capsaicin, Nociception and Pain. Molecules. 2016;21:797.
   Web of Science ®Google Scholar
• Baron R, Allegri M, Correa-Illanes G, et al. The 5% lidocaine-medicated plaster: its inclusion in international treatment guidelines for treating localized neuropathic pain, and clinical evidence supporting its use. Pain Ther. 2016;5:149–169.
   PubMed Web of Science ®Google Scholar
• Sawynok J. Topical analgesics for neuropathic pain: preclinical exploration, clinical validation, future development: topical analgesics for neuropathic pain. EJP. 2014;18:465–481.
   PubMed Web of Science ®Google Scholar
• Wehrfritzl A, Namerl B, Ihmsenl H, et al. Differential effects on sensory functions and measures of epidermal nerve fiber density after application of a lidocaine patch (5%) on healthy human skin. Eur J Pain. 2011;15:907–912.
   PubMed Web of Science ®Google Scholar
• Derry S, Wiffen PJ, Kalso EA, et al. Topical analgesics for acute and chronic pain in adults - an overview of cochrane reviews. Cochrane Database Syst Rev. 2017;5:CD008609.
   PubMed Web of Science ®Google Scholar
• Palladini M, Boesl I, Koenig S, et al. Lidocaine medicated plaster, an additional potential treatment option for localized post-surgical neuropathic pain: efficacy and safety results of a randomized, placebo-controlled trial. Curr Med Res Opin. 2019;35:757–766.
   PubMed Web of Science ®Google Scholar
• Kim Y-C, Castañeda AM, Lee C-S, et al. Efficacy and safety of lidocaine infusion treatment for neuropathic pain: a randomized, double-blind, and placebo-controlled study. Reg Anesth Pain Med. 2018;43:415–424.
   PubMed Web of Science ®Google Scholar
• Demant DT, Lund K, Finnerup NB, et al. Pain relief with lidocaine 5% patch in localized peripheral neuropathic pain in relation to pain phenotype: a randomised, double-blind, and placebo-controlled, phenotype panel study. Pain. 2015;156:2234–2244.
   PubMed Web of Science ®Google Scholar
• Binder A, Bruxelle J, Rogers P, et al. Topical 5% lidocaine (lignocaine) medicated plaster treatment for post-herpetic neuralgia: results of a double-blind, placebo-controlled, multinational efficacy and safety trial. Clin Drug Investig. 2009;29:393–408.
   PubMed Web of Science ®Google Scholar
• Cheville AL, Sloan JA, Northfelt DW, et al. Use of a lidocaine patch in the management of postsurgical neuropathic pain in patients with cancer: a phase III double-blind crossover study (N01CB). Support Care Cancer. 2009;17:451–460.
   PubMed Web of Science ®Google Scholar
• Ho K-Y, Huh BK, White WD, et al. Topical amitriptyline versus lidocaine in the treatment of neuropathic pain. Clin J Pain. 2008;24:51–55.
   PubMed Web of Science ®Google Scholar
• Estanislao L, Carter K, McArthur J, et al. A randomized controlled trial of 5% lidocaine gel for HIV-associated distal symmetric polyneuropathy. J Acquir Immune Defic Syndr. 2004;37:1584–1586.
   PubMed Web of Science ®Google Scholar
• Meier T, Wasner G, Faust M, et al. Efficacy of lidocaine patch 5% in the treatment of focal peripheral neuropathic pain syndromes: a randomized, double-blind, placebo-controlled study. Pain. 2003;106:151–158.
   PubMed Web of Science ®Google Scholar
• Galer BS, Jensen MP, Ma T, et al. The lidocaine patch 5% effectively treats all neuropathic pain qualities: results of a randomized, double-blind, vehicle-controlled, 3-week efficacy study with use of the neuropathic pain scale. Clin J Pain. 2002;18:297–301.
   PubMed Web of Science ®Google Scholar
• Park J, Park HJ. Botulinum toxin for the treatment of neuropathic pain. Toxins (Basel). 2017;9:260.
   Web of Science ®Google Scholar
• Ranoux D, Attal N, Morain F, et al. Botulinum toxin type A induces direct analgesic effects in chronic neuropathic pain. Ann Neurol. 2008;64:274–283.
   PubMed Web of Science ®Google Scholar
• Attal N, de Andrade DC, Adam F, et al. Safety and efficacy of repeated injections of botulinum toxin A in peripheral neuropathic pain (BOTNEP): a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2016;15:555–565.
   PubMed Web of Science ®Google Scholar
• Ghasemi M, Ansari M, Basiri K, et al. The effects of intradermal botulinum toxin type a injections on pain symptoms of patients with diabetic neuropathy. J Res Med Sci. 2014;19:106–111.
   PubMed Web of Science ®Google Scholar
• Chen W-T, Yuan R-Y, Chiang S-C, et al. Onabotulinumtoxin A improves tactile and mechanical pain perception in painful diabetic polyneuropathy. Clin J Pain. 2013;29:305–310.
   PubMed Web of Science ®Google Scholar
• Yuan RY, Sheu JJ, Yu JM, et al. Botulinum toxin for diabetic neuropathic pain: a randomized double-blind crossover trial. Neurology. 2009;72:1473–1478.
   PubMed Web of Science ®Google Scholar
• Wei J, Zhu X, Yang G, et al. The efficacy and safety of botulinum toxin type A in treatment of trigeminal neuralgia and peripheral neuropathic pain: a meta-analysis of randomized controlled trials. Brain Behav. 2019;9:e01409.
   PubMed Web of Science ®Google Scholar
• Machado D, Martimbianco ALC, Bussadori SK, et al. Botulinum toxin type A for painful temporomandibular disorders: systematic review and meta-analysis. J Pain. 2020;21:281–293.
   Google Scholar
• Dong Y, Wu T, Hu X, et al. Efficacy and safety of botulinum toxin type A for upper limb spasticity after stroke or traumatic brain injury: a systematic review with meta-analysis and trial sequential analysis. Eur J Phys Rehabil Med. 2017;53:256–267.
   PubMed Web of Science ®Google Scholar
• Jo JK, Kim KN, Kim DW, et al. The effect of onabotulinumtoxinA according to site of injection in patients with overactive bladder: a systematic review and meta-analysis. World J Urol. 2018;36:305–317.
   PubMed Web of Science ®Google Scholar
• Scholz J, Finnerup NB, Attal N, et al. The IASP classification of chronic pain for ICD-11: chronic neuropathic pain. Pain. 2019;160:53–59.
   PubMed Web of Science ®Google Scholar
• Kerckhove N, Collin A, Condé S, et al. Long-term effects, pathophysiological mechanisms, and risk factors of chemotherapy-induced peripheral neuropathies: a comprehensive literature review. Front Pharmacol. 2017;8:86.
   PubMed Web of Science ®Google Scholar
• Gaskell H, Derry S, Stannard C, et al. Oxycodone for neuropathic pain in adults. Cochrane Database Syst Rev. 2016;7:CD010692.
   PubMedGoogle Scholar
• Derry S, Stannard C, Cole P, et al. Fentanyl for neuropathic pain in adults. Cochrane Database Syst Rev. 2016;10:CD011605.
   PubMedGoogle Scholar
• Cooper TE, Chen J, Wiffen PJ, et al. Morphine for chronic neuropathic pain in adults. Cochrane Database Syst Rev. 2017;5:CD011669.
   PubMedGoogle Scholar
• Duehmke RM, Derry S, Wiffen PJ, et al. Tramadol for neuropathic pain in adults. Cochrane Database Syst Rev. 2017;6:CD003726.
   PubMedGoogle Scholar
• United Nations Office on Drugs and Crime. World drug report 2012. [Internet]. New York: United Nations; 2012 [cited 2020 May 29]. Available from: http://search.ebscohost.com/login.aspx?direct=true&scope=site&db=nlebk&db=nlabk&AN=464981.
   Google Scholar
• United Nations Office on Drugs and Crime. International standards for the treatment of drug use disorders [internet]. World Health Organization; 2017. [cited 2020 Jun 2]. Available from: https://www.unodc.org/documents/drug-prevention-and-treatment/UNODC_International_Standards_for_the_Treatment_of_Drug_Use_Disorders_March_17_ebook.pdf.
   Google Scholar
• Grella CE, Lovinger K. 30-year trajectories of heroin and other drug use among men and women sampled from methadone treatment in California. Drug Alcohol Depend. 2011;118:251–258.
   PubMed Web of Science ®Google Scholar
• Cepeda MS, Fife D, Ma Q, et al. Comparison of the risks of opioid abuse or dependence between tapentadol and oxycodone: results from a cohort study. J Pain. 2013;14:1227–1241.
   PubMed Web of Science ®Google Scholar
• Faria J, Barbosa J, Moreira R, et al. Comparative pharmacology and toxicology of tramadol and tapentadol. Eur J Pain. 2018;22:827–844.
   PubMed Web of Science ®Google Scholar
• Aviram J, Samuelly-Leichtag G. Efficacy of cannabis-based medicines for pain management: a systematic review and meta-analysis of randomized controlled trials. Pain Physician. 2017;20:E755–E796.
   PubMed Web of Science ®Google Scholar
• Bohnert ASB, Ilgen MA, Ingelfinger JR. Understanding links among opioid use, overdose, and suicide. N Engl J Med. 2019;380:71–79.
   PubMed Web of Science ®Google Scholar
• Singh S, Loke YK. Drug safety assessment in clinical trials: methodological challenges and opportunities. Trials. 2012;13:138.
   PubMed Web of Science ®Google Scholar
• Schulz KF, Altman DG, Moher D, et al. CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. BMJ. 2010;340:c332.
   PubMed Web of Science ®Google Scholar
• Cai X, Gewandter JS, He H, et al. Estimands and missing data in clinical trials of chronic pain treatments: advances in design and analysis. Pain. 2020;161:2308–2320.
   PubMed Web of Science ®Google Scholar