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. 2017 Jul 6;7(7):CD012592.
doi: 10.1002/14651858.CD012592.pub2.

Opioids for cancer pain - an overview of Cochrane reviews

Philip J Wiffen  1 , Bee Wee, Sheena Derry, Rae F Bell, R Andrew Moore
Affiliations

Opioids for cancer pain - an overview of Cochrane reviews

Philip J Wiffen et al. Cochrane Database Syst Rev. .

Abstract

Background: Pain is a common symptom with cancer, and 30% to 50% of all people with cancer will experience moderate to severe pain that can have a major negative impact on their quality of life. Opioid (morphine-like) drugs are commonly used to treat moderate or severe cancer pain, and are recommended for this purpose in the World Health Organization (WHO) pain treatment ladder. The most commonly-used opioid drugs are buprenorphine, codeine, fentanyl, hydrocodone, hydromorphone, methadone, morphine, oxycodone, tramadol, and tapentadol.

Objectives: To provide an overview of the analgesic efficacy of opioids in cancer pain, and to report on adverse events associated with their use.

Methods: We identified systematic reviews examining any opioid for cancer pain published to 4 May 2017 in the Cochrane Database of Systematic Reviews in the Cochrane Library. The primary outcomes were no or mild pain within 14 days of starting treatment, withdrawals due to adverse events, and serious adverse events.

Main results: We included nine reviews with 152 included studies and 13,524 participants, but because some studies appeared in more than one review the number of unique studies and participants was smaller than this. Most participants had moderate or severe pain associated with a range of different types of cancer. Studies in the reviews typically compared one type of opioid or formulation with either a different formulation of the same opioid, or a different opioid; few included a placebo control. Typically the reviews titrated dose to effect, a balance between pain relief and adverse events. Various routes of administration of opioids were considered in the reviews; oral with most opioids, but transdermal administration with fentanyl, and buprenorphine. No review included studies of subcutaneous opioid administration. Pain outcomes reported were varied and inconsistent. The average size of included studies varied considerably between reviews: studies of older opioids, such as codeine, morphine, and methadone, had low average study sizes while those involving newer drugs tended to have larger study sizes.Six reviews reported a GRADE assessment (buprenorphine, codeine, hydromorphone, methadone, oxycodone, and tramadol), but not necessarily for all comparisons or outcomes. No comparative analyses were possible because there was no consistent placebo or active control. Cohort outcomes for opioids are therefore reported, as absolute numbers or percentages, or both.Reviews on buprenorphine, codeine with or without paracetamol, hydromorphone, methadone, tramadol with or without paracetamol, tapentadol, and oxycodone did not have information about the primary outcome of mild or no pain at 14 days, although that on oxycodone indicated that average pain scores were within that range. Two reviews, on oral morphine and transdermal fentanyl, reported that 96% of 850 participants achieved that goal.Adverse event withdrawal was reported by five reviews, at rates of between 6% and 19%. Participants with at least one adverse event were reported by three reviews, at rates of between 11% and 77%.Our GRADE assessment of evidence quality was very low for all outcomes, because many studies in the reviews were at high risk of bias from several sources, including small study size.

Authors' conclusions: The amount and quality of evidence around the use of opioids for treating cancer pain is disappointingly low, although the evidence we have indicates that around 19 out of 20 people with moderate or severe pain who are given opioids and can tolerate them should have that pain reduced to mild or no pain within 14 days. This accords with the clinical experience in treating many people with cancer pain, but overstates to some extent the effectiveness found for the WHO pain ladder. Most people will experience adverse events, and help may be needed to manage the more common undesirable adverse effects such as constipation and nausea. Perhaps between 1 in 10 and 2 in 10 people treated with opioids will find these adverse events intolerable, leading to a change in treatment.

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Conflict of interest statement

PW: none known.

BW: none known; BW is a specialist palliative care physician and manages patients with cancer pain.

SD: none known.

RFB: none known. RFB is a retired specialist pain physician who has worked with patients having acute, chronic or cancer pain, including palliative care patients.

RAM has received grant support from Grünenthal relating to individual patient‐level analyses of trial data regarding tapentadol in osteoarthritis and back pain (2015). He has received honoraria for attending boards with Menarini concerning methods of analgesic trial design (2014), with Novartis (2014) about the design of network meta‐analyses, and RB on understanding pharmacokinetics of drug uptake (2015). He has received honoraria from Omega Pharma (2016) and Futura Pharma (2016) for providing advice on trial and data analysis methods.

This review was identified in a 2019 audit as not meeting the current definition of the Cochrane Commercial Sponsorship policy. At the time of its publication it was compliant with the interpretation of the existing policy. As with all reviews, new and updated, at update this review will be revised according to 2020 policy update.

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  • doi: 10.1002/14651858.CD012592

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References

References to included reviews

Bao 2016
    1. Bao YJ, Hou W, Kong XY, Yang L, Xia J, Hua BJ, et al. Hydromorphone for cancer pain. Cochrane Database of Systematic Reviews 2016, Issue 10. [DOI: 10.1002/14651858.CD011108.pub2] - DOI - PMC - PubMed
Hadley 2013
    1. Hadley G, Derry S, Moore RA, Wiffen PJ. Transdermal fentanyl for cancer pain. Cochrane Database of Systematic Reviews 2013, Issue 10. [DOI: 10.1002/14651858.CD010270.pub2] - DOI - PMC - PubMed
Nicholson 2017
    1. Nicholson AB, Watson GR, Derry S, Wiffen PJ. Methadone for cancer pain. Cochrane Database of Systematic Reviews 2017, Issue 2. [DOI: 10.1002/14651858.CD003971.pub4] - DOI - PMC - PubMed
Schmidt‐Hansen 2015a
    1. Schmidt‐Hansen M, Bennett MI, Arnold S, Bromham N, Hilgart JS. Oxycodone for cancer‐related pain. Cochrane Database of Systematic Reviews 2015, Issue 2. [DOI: 10.1002/14651858.CD003870.pub5] - DOI - PubMed
Schmidt‐Hansen 2015b
    1. Schmidt‐Hansen M, Bromham N, Taubert M, Arnold S, Hilgart JS. Buprenorphine for treating cancer pain. Cochrane Database of Systematic Reviews 2015, Issue 3. [DOI: 10.1002/14651858.CD009596.pub4] - DOI - PMC - PubMed
Straube 2014
    1. Straube C, Derry S, Jackson KC, Wiffen PJ, Bell RF, Strassels S, et al. Codeine, alone and with paracetamol (acetaminophen), for cancer pain. Cochrane Database of Systematic Reviews 2014, Issue 9. [DOI: 10.1002/14651858.CD006601.pub4] - DOI - PMC - PubMed
Wiffen 2015
    1. Wiffen PJ, Derry S, Naessens K, Bell RF. Oral tapentadol for cancer pain. Cochrane Database of Systematic Reviews 2015, Issue 9. [DOI: 10.1002/14651858.CD011460.pub2] - DOI - PMC - PubMed
Wiffen 2016
    1. Wiffen PJ, Wee B, Moore RA. Oral morphine for cancer pain. Cochrane Database of Systematic Reviews 2016, Issue 4. [DOI: 10.1002/14651858.CD003868.pub4] - DOI - PMC - PubMed
Wiffen 2017c
    1. Wiffen PJ, Derry S, Moore RA. Tramadol with or without paracetamol (acetaminophen) for cancer pain. Cochrane Database of Systematic Reviews 2017, Issue 1. [DOI: 10.1002/14651858.CD012508] - DOI - PMC - PubMed

References to excluded reviews

Wiffen 2014
    1. Wiffen PJ, Derry S, Moore RA. Impact of morphine, fentanyl, oxycodone or codeine on patient consciousness, appetite and thirst when used to treat cancer pain. Cochrane Database of Systematic Reviews 2014, Issue 5. [DOI: 10.1002/14651858.CD011056.pub2] - DOI - PMC - PubMed

Additional references

AlBalawi 2013
    1. AlBalawi Z, McAlister FA, Thorlund K, Wong M, Wetterslev J. Random error in cardiovascular meta‐analyses: how common are false positive and false negative results?. International Journal of Cardiology 2013;168(2):1102‐7. [DOI: 10.1016/j.ijcard.2012.11.048] - DOI - PubMed
Azevedo São Leão Ferreira 2006
    1. Azevedo São Leão Ferreira K, Kimura M, Jacobsen Teixeira M. The WHO analgesic ladder for cancer pain control, twenty years of use. How much pain relief does one get from using it?. Supportive Care in Cancer 2006;14(11):1086‐93. [DOI: 10.1007/s00520-006-0086-x] - DOI - PubMed
Ball 1985
    1. Ball M, McQuay HJ, Moore RA, Allen MC, Fisher A, Sear J. Renal failure and the use of morphine in intensive care. Lancet 1985;1(8432):784‐6. [DOI: 10.1016/S0140-6736(85)91448-5] - DOI - PubMed
Breivik 2009
    1. Breivik H, Cherny N, Collett B, Conno F, Filbet M, Foubert AJ, et al. Cancer‐related pain: a pan‐European survey of prevalence, treatment, and patient attitudes. Annals of Oncology 2009;20(8):1420‐33. [DOI: 10.1093/annonc/mdp001] - DOI - PubMed
Brok 2009
    1. Brok J, Thorlund K, Wetterslev J, Gluud C. Apparently conclusive meta‐analyses may be inconclusive ‐ trial sequential analysis adjustment of random error risk due to repetitive testing of accumulating data in apparently conclusive neonatal meta‐analyses. International Journal of Epidemiology 2009;38(1):287‐98. [DOI: 10.1093/ije/dyn188] - DOI - PubMed
Caraceni 2012
    1. Caraceni A, Hanks G, Kaasa S, Bennett M, Brunelli C, Cherny N, et al. for the European Palliative Research Collaborative (EPCRC), on behalf of the European Association for Palliative Care (EAPC). Use of opioid analgesics in the treatment of cancer pain: evidence‐based recommendations from the EAPC. Lancet Oncology 2012;13(2):e58‐68. [DOI: 10.1016/S1470-2045(12)70040-2] - DOI - PubMed
Carlson 2016
    1. Carlson CL. Effectiveness of the World Health Organization cancer pain relief guidelines: an integrative review. Journal of Pain Research 2016;9:515‐34. [DOI: 10.2147/JPR.S97759] - DOI - PMC - PubMed
Cascorbi 2003
    1. Cascorbi I. Pharmacogenetics of cytochrome P4502D6: genetic background and clinical implication. European Journal of Clinical Investigation 2003;33 (Suppl 2):17‐22. [PUBMED: 14641552] - PubMed
Ciszkowski 2009
    1. Ciszkowski C, Madadi P, Phillips MS, Lauwers AE, Koren G. Codeine, ultrarapid‐metabolism genotype, and postoperative death. New England Journal of Medicine 2009;361(8):827‐8. [DOI: 10.1056/NEJMc0904266] - DOI - PubMed
Collins 1998
    1. Collins SL, Faura CC, Moore RA, McQuay HJ. Peak plasma concentrations after oral morphine: a systematic review. Journal of Pain and Symptom Management 1998;16(6):388‐402. [DOI: 10.1016/S0885-3924(98)00094-3] - DOI - PubMed
Cook 1995
    1. Cook RJ, Sackett DL. The number needed to treat: a clinically useful measure of treatment effect. BMJ (Clinical Research Ed.) 1995;310(6977):452‐4. [DOI: 10.1136/bmj.310.6977.452] - DOI - PMC - PubMed
CRUK 2014
    1. Cancer Research UK. Cancer Statistics for the UK. www.cancerresearchuk.org/health‐professional/cancer‐statistics (accessed 10 April 2017).
Deandrea 2008
    1. Deandrea S, Montanari M, Moja L, Apolone G. Prevalence of undertreatment in cancer pain. A review of published literature. Annals of Oncology 2008;19(12):1985‐91. [DOI: 10.1093/annonc/mdn419] - DOI - PMC - PubMed
Dechartres 2013
    1. Dechartres A, Trinquart L, Boutron I, Ravaud P. Influence of trial sample size on treatment effect estimates: meta‐epidemiological study. BMJ 2013;346:f2304. [DOI: 10.1136/bmj.f2304] - DOI - PMC - PubMed
Dechartres 2014
    1. Dechartres A, Altman DG, Trinquart L, Boutron I, Ravaud P. Association between analytic strategy and estimates of treatment outcomes in meta‐analyses. JAMA 2014;312(6):623‐30. [DOI: 10.1001/jama.2014.8166] - DOI - PubMed
Deng 2012
    1. Deng D, Fu L, Zhao YX, Wu X, Zhang G, Liang C, et al. The relationship between cancer pain and quality of life in patients newly admitted to Wuhan Hospice Center of China. American Journal of Hospice & Palliative Care 2012;29(1):53‐9. [DOI: 10.1177/1049909111418636] - DOI - PubMed
Derry 2017
    1. Derry S, Wiffen PJ, Moore RA, McNicol ED, Bell RF, Carr DB, et al. Oral nonsteroidal anti‐inflammatory drugs (NSAIDs) for cancer pain in adults. Cochrane Database of Systematic Reviews 2017, Issue 4. [DOI: 10.1002/14651858.CD012638] - DOI - PMC - PubMed
Dreidi 2016
    1. Dreidi MM, Hamdan‐Mansour AM. Pain, sleep disturbance, and quality of life among Palestinian patients diagnosed with cancer. Journal of Cancer Education 2016;31(4):796‐803. [DOI: 10.1007/s13187-015-0946-5] - DOI - PubMed
Dworkin 2008
    1. Dworkin RH, Turk DC, Wyrwich KW, Beaton D, Cleeland CS, Farrar JT, et al. Interpreting the clinical importance of treatment outcomes in chronic pain clinical trials: IMMPACT recommendations. Journal of Pain 2008;9(2):105‐21. [DOI: 10.1016/j.jpain.2007.09.005] - DOI - PubMed
EPOC 2015
    1. Anon. EPOC author resources. epoc.cochrane.org/epoc‐specific‐resources‐review‐authors (accessed 10 April 2017) 2015.
Fallon 2011
    1. Fallon MT, Laird BJ. A systematic review of combination step III opioid therapy in cancer pain: an EPCRC opioid guideline project. Palliative Medicine 2011;25(5):597‐603. [DOI: 10.1177/0269216310392101] - DOI - PubMed
Fanelli 2017
    1. Fanelli D, Costas R, Ioannidis JP. Meta‐assessment of bias in science. Proceedings of the National Academy of Sciences of the USA 2017 Mar 20 [Epub ahead of print];114(14):3714‐9. [DOI: 10.1073/pnas.1618569114] - DOI - PMC - PubMed
Faura 1996
    1. Faura CC, Moore RA, Horga JF, Hand CW, McQuay HJ. Morphine and morphine‐6‐glucuronide plasma concentrations and effect in cancer pain. Journal of Pain and Symptom Management 1996;11(2):95‐102. [DOI: 10.1016/0885-3924(95)00148-4] - DOI - PubMed
Faura 1998
    1. Faura CC, Collins SL, Moore RA, McQuay HJ. Systematic review of factors affecting the ratios of morphine and its major metabolites. Pain 1998;74(1):43‐53. [DOI: 10.1016/S0304-3959(97)00142-5] - DOI - PubMed
Glenny 2005
    1. Glenny AM, Altman DG, Song F, Sakarovitch C, Deeks JJ, D'Amico R, et al. International Stroke Trial Collaborative Group. Indirect comparisons of competing interventions. Health Technology Assessment 2005;9(26):1‐134, iii‐iv. [DOI: 10.3310/hta9260] - DOI - PubMed
Grahame‐Smith 2002
    1. Grahame‐Smith DG, Aronson JK. Oxford Textbook of Clinical Pharmacology and Drug Therapy. 3rd Edition. Oxford: Oxford University Press, 2002. [ISBN: 978‐0192632340]
Guyatt 2011
    1. Guyatt GH, Oxman AD, Kunz R, Woodcock J, Brozek J, Helfand M, et al. GRADE guidelines: 7. Rating the quality of evidence‐‐inconsistency. Journal of Clinical Epidemiology 2011;64(12):1294‐302. [DOI: 10.1016/j.jclinepi.2011.03.017] - DOI - PubMed
Guyatt 2013a
    1. Guyatt G, Oxman AD, Sultan S, Brozek J, Glasziou P, Alonso‐Coello P, et al. GRADE guidelines: 11. Making an overall rating of confidence in effect estimates for a single outcome and for all outcomes. Journal of Clinical Epidemiology 2013;66(2):151‐7. [DOI: 10.1016/j.jclinepi.2012.01.006] - DOI - PubMed
Guyatt 2013b
    1. Guyatt GH, Oxman AD, Santesso N, Helfand M, Vist G, Kunz R, et al. GRADE guidelines: 12. Preparing summary of findings tables‐binary outcomes. Journal of Clinical Epidemiology 2013;66(2):158‐72. [DOI: 10.1016/j.jclinepi.2012.01.012] - DOI - PubMed
Higgins 2011
    1. Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.
IARC 2012
    1. International Agency for Research on Cancer. GLOBOCAN 2012: Estimated cancer incidence, mortality and prevalence worldwide in 2012. globocan.iarc.fr/Pages/fact_sheets_cancer.aspx (accessed 10 April 2017).
Jacox 1994
    1. Jacox A, Carr DB, Payne R, Berde CB, Brietbart W, Cain JM, et al. Management of Cancer Pain. Clinical Practice Guideline No. 9. AHCPR Publication No. 94‐0592. Rockville, MD: Agency for Health Care Policy and Research, U.S. Department of Health and Human Services, Public Health Service, 1994.
Jadad 1995
    1. Jadad AR, Browman GP. The WHO analgesic ladder for cancer pain management. Stepping up the quality of its evaluation. JAMA 1995;274(23):1870‐3. [DOI: 10.1001/jama.1995.03530230056031] - DOI - PubMed
Madadi 2007
    1. Madadi P, Koren G, Cairns J, Chitayat D, Gaedigk A, Leeder JS, et al. Safety of codeine during breastfeeding: fatal morphine poisoning in the breastfed neonate of a mother prescribed codeine. Canadian Family Physician Medecin de Famille Canadien 2007;53(1):33‐5. [PUBMED: 17872605] - PMC - PubMed
Mandal 2013
    1. Mandal A. Morphine pharmacology. www.news‐medical.net/health/Morphine‐Pharmacology.aspx (accessed 10 April 2017) Last updated 2013.
Mercadante 2016
    1. Mercadante S, Marchetti P, Cuomo A, Mammucari M, Caraceni A, IOPS MS study Group. Breakthrough pain and its treatment: critical review and recommendations of IOPS (Italian Oncologic Pain Survey) expert group. Supportive Care in Cancer 2016;24(2):961‐8. [DOI: 10.1007/s00520-015-2951-y] - DOI - PubMed
Miaskowski 2005
    1. Miaskowski C, Cleary J, Burney R, Coyne P, Finley R, Foster R, et al. Guideline for the Management of Cancer Pain in Adults and Children, APS Clinical Practice Guideline Series, No. 3. Glenview, IL: American Pain Society, 2005.
Mikan 2016
    1. Mikan F, Wada M, Yamada M, Takahashi A, Onishi H, Ishida M, et al. The association between pain and quality of life for patients with cancer in an outpatient clinic, an inpatient oncology ward, and inpatient palliative care units. American Journal of Hospice & Palliative Care 2016;33(8):782‐90. [DOI: 10.1177/1049909116630266] - DOI - PubMed
Moore 1998
    1. Moore RA, Gavaghan D, Tramèr MR, Collins SL, McQuay HJ. Size is everything ‐ large amounts of information are needed to overcome random effects in estimating direction and magnitude of treatment effects. Pain 1998;78(3):209‐16. [DOI: 10.1016/S0304-3959(98)00140-7] - DOI - PubMed
Moore 2008
    1. Moore RA, Barden J, Derry S, McQuay HJ. Managing potential publication bias. In: McQuay HJ, Kalso E, Moore RA editor(s). Systematic Reviews in Pain Research: Methodology Refined. Seattle: IASP Press, 2008:15‐23. [ISBN: 978‐0‐931092‐69‐5]
Moore 2010
    1. Moore RA, Derry S, McQuay HJ, Straube S, Aldington D, Wiffen P, et al. Clinical effectiveness: an approach to clinical trial design more relevant to clinical practice, acknowledging the importance of individual differences. Pain 2010;149(2):173‐6. [DOI: 10.1016/j.pain.2009.08.007] - DOI - PubMed
Moore 2013
    1. Moore RA, Straube S, Aldington D. Pain measures and cut‐offs ‐ 'no worse than mild pain' as a simple, universal outcome. Anaesthesia 2013;68(4):400‐12. [DOI: 10.1111/anae.12148] - DOI - PubMed
Moore 2014
    1. Moore RA, Derry S, Taylor RS, Straube S, Phillips CJ. The costs and consequences of adequately managed chronic non‐cancer pain and chronic neuropathic pain. Pain Practice 2014;14(1):79‐94. [DOI: 10.1111/papr.12050] - DOI - PubMed
Moore 2015
    1. Moore RA, Derry S, Aldington D, Wiffen PJ. Single dose oral analgesics for acute postoperative pain in adults ‐ an overview of Cochrane reviews. Cochrane Database of Systematic Reviews 2015, Issue 9. [DOI: 10.1002/14651858.CD008659.pub3] - DOI - PMC - PubMed
Morris 1995
    1. Morris JA, Gardner MJ. Calculating confidence intervals for relative risk, odds ratios and standardised ratios and rates. In: Gardner MJ, Altman DG editor(s). Statistics with Confidence ‐ Confidence Intervals and Statistical Guidelines. London: British Medical Journal, 1995:50‐63. - PMC - PubMed
Nguyen 2017
    1. Nguyen TL, Collins GS, Lamy A, Devereaux PJ, Daurès JP, Landais P, et al. Simple randomization did not protect against bias in smaller trials. Journal of Clinical Epidemiology 2017 Feb 29 [Epub ahead of print];84:105‐13. [DOI: 10.1016/j.jclinepi.2017.02.010] - DOI - PubMed
NICE 2016
    1. National Institute for Health and Care Excellence. Palliative care for adults: strong opioids for pain relief. Guideline CG140. www.nice.org.uk/guidance/cg140 2016 (accessed 10 April 2017).
Nüesch 2010
    1. Nüesch E, Trelle S, Reichenbach S, Rutjes AW, Tschannen B, Altman DG, et al. Small study effects in meta‐analyses of osteoarthritis trials: meta‐epidemiological study. BMJ 2010;341:c3515. [DOI: 10.1136/bmj.c3515] - DOI - PMC - PubMed
Opiates 2013
    1. Anon. Codeine. www.opiates.com/codeine/ (accessed 10 April 2017) 2013.
Paul 1989
    1. Paul D, Standifer KM, Inturrisi CE, Pasternak GW. Pharmacological characterization of morphine‐6 beta‐glucuronide, a very potent morphine metabolite. Journal of Pharmacology and Experimental Therapeutics 1989;251(2):477‐83. [PUBMED: 2810109] - PubMed
PCA 2016
    1. Prescribing & Medicines Team. Prescription Cost Analysis England 2016. Health and Social Care Information Centre 2017 (April). [ISBN: 978‐1‐78386‐680‐9]
Portenoy 1999
    1. Portenoy RK, Lesage P. Management of cancer pain. Lancet 1999;353(9165):1695‐700. [DOI: 10.1016/S0140-6736(99)01310-0] - DOI - PubMed
Prommer 2015
    1. Prommer EE. Pharmacological Management of Cancer‐Related Pain. Cancer Control 2015;22(4):412‐25. [PUBMED: 26678968] - PubMed
Rey 1993
    1. Rey R. History of Pain. Paris: Editions La Decouverte, 1993. [ISBN: 2‐7071‐2256‐4]
Ripamonti 2012a
    1. Ripamonti CI, Santini D, Maranzano E, Berti M, Roila F, ESMO Guidelines Working Group. Management of cancer pain: ESMO Clinical Practice Guidelines. Annals of Oncology 2012;23 (Suppl 7):vii139‐54. [DOI: 10.1093/annonc/mds233] - DOI - PubMed
Ripamonti 2012b
    1. Ripamonti CI. Pain management. Annals of Oncology 2012;23 (Suppl 10):x294‐x301. [DOI: 10.1093/annonc/mds360] - DOI - PubMed
Roberts 2015
    1. Roberts I, Ker K, Edwards P, Beecher D, Manno D, Sydenham E. The knowledge system underpinning healthcare is not fit for purpose and must change. BMJ 2015;350:h2463. [DOI: 10.1136/bmj.h2463] - DOI - PubMed
Sear 1985
    1. Sear J, Moore A, Hunniset A, Baldwin D, Allen M, Hand C, et al. Morphine kinetics and kidney transplantation: morphine removal is influenced by renal ischemia. Anesthesia and Analgesia 1985;64(11):1065‐70. [PUBMED: 3901820] - PubMed
Sear 1989
    1. Sear JW, Hand CW, Moore RA, McQuay HJ. Studies on morphine disposition: influence of renal failure on the kinetics of morphine and its metabolites. British Journal of Anaesthesia 1989;62(1):28‐32. [DOI: 10.1093/bja/62.1.22] - DOI - PubMed
Shea 2007
    1. Shea BJ, Grimshaw JM, Wells GA, Boers M, Andersson N, Hamel C, et al. Development of AMSTAR: a measurement tool to assess the methodological quality of systematic reviews. BMC Medical Research Methodology 2007;7:10. [DOI: 10.1186/1471-2288-7-10] - DOI - PMC - PubMed
SIGN 2008
    1. Scottish Intercollegiate Guidelines Network. Control of pain in adults with cancer. A national clinical guideline. www.sign.ac.uk/pdf/SIGN106.pdf (accessed 10 April 2017). Edinburgh: Scottish Intercollegiate Guidelines Network, 2008.
Song 2003
    1. Song F, Altman DG, Glenny AM, Deeks JJ. Validity of indirect comparison for estimating efficacy of competing interventions: empirical evidence from published meta‐analyses. BMJ 2003;326(7387):472. [DOI: 10.1136/bmj.326.7387.472] - DOI - PMC - PubMed
Stewart 2014
    1. Stewart BW, Wild CP. World Cancer Report 2014. Lyon: International Agency for Research on Cancer, 2014. [ISBN: 978‐92‐832‐0443‐5]
Thorlund 2011
    1. Thorlund K, Imberger G, Walsh M, Chu R, Gluud C, Wetterslev J, et al. The number of patients and events required to limit the risk of overestimation of intervention effects in meta‐analysis‐‐a simulation study. PLoS One 2011;6(10):e25491. [DOI: 10.1371/journal.pone.0025491] - DOI - PMC - PubMed
Thornton 2000
    1. Thornton A, Lee P. Publication bias in meta‐analysis: its causes and consequences. Journal of Clinical Epidemiology 2000;53(2):207‐16. [DOI: 10.1016/S0895-4356(99)00161-4] - DOI - PubMed
Turner 2013
    1. Turner RM, Bird SM, Higgins JP. The impact of study size on meta‐analyses: examination of underpowered studies in Cochrane reviews. PLOS One 2013;8(3):e59202. [DOI: 10.1371/journal.pone.0059202] - DOI - PMC - PubMed
van den Beuken‐van Everdingen 2016
    1. Beuken‐van Everdingen MH, Hochstenbach LM, Joosten EA, Tjan‐Heijnen VC, Janssen DJ. Update on prevalence of pain in patients with cancer: systematic review and meta‐analysis. Journal of Pain and Symptom Management 2016;51(6):1070‐90. [DOI: 10.1016/j.jpainsymman.2015.12.340] - DOI - PubMed
WHO 1986
    1. World Health Organization. Cancer Pain Relief. apps.who.int/iris/bitstream/10665/43944/1/9241561009_eng.pdf (accessed 10 April 2017) 1986.
WHO 1996
    1. World Health Organization. WHO Cancer Pain Relief ‐ a Guide to Opioid Availability, 2nd Edition. apps.who.int/iris/bitstream/10665/37896/1/9241544821.pdf (accessed 10 April 2017) 1996.
WHO 2011
    1. World Health Organization. WHO Essential Medicines List. 17th list. apps.who.int/iris/bitstream/10665/70640/1/a95053_eng.pdf (accessed 10 April 2017) 2011.
Wiffen 2017a
    1. Wiffen PJ, Derry S, Moore RA, McNicol ED, Bell RF, Carr DB, et al. Oral paracetamol (acetaminophen) for cancer pain. Cochrane Database of Systematic Reviews 2017, Issue 4. [DOI: 10.1002/14651858.CD012637] - DOI - PMC - PubMed
Wiffen 2017b
    1. Wiffen PJ, Cooper TE, Anderson AK, Gray AL, Grégoire MC, Ljungman G, et al. Opioids for cancer‐related pain in children and adolescents. Cochrane Database of Systematic Reviews 2017, Issue 2. [DOI: 10.1002/14651858.CD012564] - DOI - PMC - PubMed
Wittwer 2006
    1. Wittwer E, Kern SE. Role of morphine's metabolites in analgesia: concepts and controversies. AAPS Journal 2006;8(2):E348‐52. [DOI: 10.1007/BF02854905] - DOI - PMC - PubMed
Zin 2014
    1. Zin CS, Chen LC, Knaggs RD. Changes in trends and pattern of strong opioid prescribing in primary care. European Journal of Pain (London, England) 2014;18(9):1343‐51. [DOI: 10.1002/j.1532-2149.2014.496.x] - DOI - PMC - PubMed

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