A cluster randomized trial to measure the impact on nonsteroidal anti-inflammatory drug and proton pump inhibitor prescribing in Italy of distributing cost-free paracetamol to osteoarthritic patients

Massimo Vicentini, Pamela Mancuso, Paolo Giorgi Rossi, Sara Di Pede, Morena Pellati, Alberto Gandolfi, Daniela Zoboli, Daniela Riccò, Corrado Busani, Alessandra Ferretti, Massimo Vicentini, Pamela Mancuso, Paolo Giorgi Rossi, Sara Di Pede, Morena Pellati, Alberto Gandolfi, Daniela Zoboli, Daniela Riccò, Corrado Busani, Alessandra Ferretti

Abstract

Background: Paracetamol is recommended as first-line treatment for pain control in osteoarthritis because it has fewer side effects than do other therapeutic options, including nonsteroidal anti-inflammatory drugs (NSAIDs). Prescribing proton pump inhibitors (PPIs) as gastric bleeding prophylaxis in chronic NSAID users is also common, although not recommended. In Italy, paracetamol is not reimbursed by the National Health System. The aim of this trial was to test whether the availability to osteoarthritis patients of free paracetamol would decrease their use of NSAIDs and, as a secondary objective, whether opioid and PPI consumption would also decrease.

Methods: Eight general practitioners (GPs) (59 patients) were randomized to usual care and 8 (58 patients) to the experimental arm, where prescribed paracetamol was directly distributed for free by the local hospital. After 6 months, paracetamol was also available for free in the control arm. The main outcome was the pre/post difference in average NSAID and PPI consumption. Differences between experimental and control arms in pre/post differences are reported, as registered by the drug prescription information system.

Results: Average NSAID consumption decreased non-significantly, from 6.79 to 2.16 defined daily dose (DDD) in the experimental arm and from 3.19 to 2.97 DDD in the control group (p = 0.067). No changes were observed for PPIs (from 11.27 to 14.65 DDD and from 9.74 to 12.58 DDD in experimental and control arms, respectively, p = 0.788) or opioids (from 1.61 to 1.14 DDD and from 1.41 to 1.56 DDD in experimental and control arms, respectively, p = 0.419). When the intervention was extended to the control arm, no decrease in NSAID consumption was observed (from 2.46 to 2.43 DDD, p = 0.521).

Conclusions: Removing small economic barriers had small or no effect on the appropriateness of opioid or PPI prescribing to patients with osteoarthritis; a reduction in NSAID consumption cannot be ruled out.

Trial registration number: NCT02691754 (Approved February 24, 2016).

Keywords: Drug prescription; Nonsteroidal anti-inflammatory drugs; Opioids; Osteoarthritis; Paracetamol; Proton pump inhibitors.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Flowchart of randomization process and comparisons between and within arms, by period

References

    1. Institute for Health Metrics and Evaluation (IHME). GBD Compare Data Visualization. Seattle, WA: IHME, University of Washington, 2018. Available from . (Accessed Oct 2019).
    1. da Costa BR, Reichenbach S, Keller N, Nartey L, Wandel S, Jüni P, Trelle S. Effectiveness of non-steroidal anti-inflammatory drugs for the treatment of pain in knee and hip osteoarthritis: a network meta-analysis. Lancet. 2016;387(10033):2093–2105. doi: 10.1016/S0140-6736(16)30002-2.
    1. NICE clinical guideline 59 Osteoarthritis: the care and management of osteoarthritis in adults. Febbraio 2008. Disponibile al sito: (ultimo accesso 30/Sept/2010).
    1. Chou R, Fanciullo GJ, Fine PG, Adler JA, Ballantyne JC, Davies P, et al. Clinical guidelines for the use of chronic opioid therapy in chronic non-cancer pain. J Pain. 2009;10(2):113–130. doi: 10.1016/j.jpain.2008.10.008.
    1. ICSI Health Care Guideline . Assessment and Management of Chronic Pain. 2009.
    1. American Geriatric Society Pharmacological management of persistent pain in older persons. J Am Geriatr Soc. 2009;57:1331–1346. doi: 10.1111/j.1532-5415.2009.02376.x.
    1. Farrar JT, Young JP, Jr, LaMoreaux L, Werth JL, Poole RM. Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain. 2001;94:149–158. doi: 10.1016/S0304-3959(01)00349-9.
    1. Towheed TE, Maxwell L, Judd MG, Catton M, Hochberg MC, Wells G. Acetaminophen for osteoarthritis. Cochrane Database Syst Rev. 2006;1:CD004257.
    1. Maestri E, Formoso G, Giroldini R, Riccomi S, Magrini N, Marata AM. I farmaci nel dolore persistente. Fibromialgia, osteoartrosi, mal di schiena. Pacchetti Informativi sui Farmaci. 2010;1:1–16.
    1. Holt WS, Jr, Mazzuca SA. Prescribing behaviors of family physicians in the treatment of osteoarthritis. Fam Med. 1992;24(7):524–527.
    1. Luiza VL, Chaves LA, Silva RM, Emmerick IC, Chaves GC, Fonseca de Araújo SC, et al. Pharmaceutical policies: effects of cap and co-payment on rational use of medicines. Cochrane Database Syst Rev. 2015;5:CD007017.
    1. Green CJ, Maclure M, Fortin PM, Ramsay CR, Aaserud M, Bardal S. Pharmaceutical policies: effects of restrictions on reimbursement. Cochrane Database Syst Rev. 2010;8:CD008654.
    1. Fretheim A, Håvelsrud K, MacLennan G, Kristoffersen DT, Oxman AD. The effects of mandatory prescribing of thiazides for newly treated, uncomplicated hypertension: interrupted time-series analysis. PLoS Med. 2007;4(7):e232. doi: 10.1371/journal.pmed.0040232.
    1. Bjerrum L, Larsen J, Kragstrup J. Guidelines accompanied by changes in reimbursement rules. Effects on lipid-lowering drug prescribing. Scand J Prim Health Care. 2001;19(3):158–162. doi: 10.1080/028134301316982379.
    1. Jackevicius CA, Tu JV, Demers V, Melo M, Cox J, Rinfret S, Kalavrouziotis D, Johansen H, Behlouli H, Newman A, Pilote L. Cardiovascular outcomes after a change in prescription policy for clopidogrel. N Engl J Med. 2008;359(17):1802–1810. doi: 10.1056/NEJMsa0803410.
    1. Sakshaug S, Furu K, Karlstad Ø, Rønning M, Skurtveit S. Switching statins in Norway after new reimbursement policy: a nationwide prescription study. Br J Clin Pharmacol. 2007;64(4):476–481. doi: 10.1111/j.1365-2125.2007.02907.x.
    1. van Driel ML, Vander Stichele R, Elseviers M, De Sutter A, De Maeseneer J, Christiaens T. Effects of an evidence report and policies lifting reimbursement restrictions for acid suppressants: analysis of the Belgian national database. Pharmacoepidemiol Drug Saf. 2008;17(11):1113–1122. doi: 10.1002/pds.1664.
    1. Magrini N, Formoso G, Capelli O, Maestri E, Nonino F, Paltrinieri B, et al. Long term effectiveness on prescribing of two multifaceted educational interventions: results of two large scale randomized cluster trials. PLoS One. 2014;9(10):e109915. doi: 10.1371/journal.pone.0109915.
    1. Magrini N, Formoso G, Marata AM, Capelli O, Maestri E, Voci C, et al. Randomised controlled trials for evaluating the prescribing impact of information meetings led by pharmacists and of new information formats, in general practice in Italy. BMC Health Serv Res. 2007;7:158. doi: 10.1186/1472-6963-7-158.
    1. Sinnott SJ, Normand C, Byrne S, Woods N, Whelton H. Copayments for prescription medicines on a public health insurance scheme in Ireland. Pharmaco Epidemiol Drug Saf. 2015;25(6):695–704. doi: 10.1002/pds.3917.
    1. Twardella D, Brenner H. Effects of practitioner education, practitioner payment and reimbursement of patients' drug costs on smoking cessation in primary care: a cluster randomised trial. Tob Control. 2007;16(1):15–21. doi: 10.1136/tc.2006.016253.
    1. Munson JC, Wahl PM, Daniel G, Kimmel SE, Hennessy S. Factors associated with the initiation of proton pump inhibitors in corticosteroid users. Pharmacoepidemiol Drug Saf. 2012;21(4):366–374. doi: 10.1002/pds.2350.
    1. National Collaborating Centre for Chronic Conditions (UK) National Clinical Guideline for Care and Management in Adults. London: Royal College of Physicians (UK); 2008. Osteoarthritis.
    1. Kelly OB, Dillane C, Patchett SE, Harewood GC, Murray FE. The inappropriate prescription of Oral proton pump inhibitors in the hospital setting: a prospective cross-sectional study. Dig Dis Sci. 2015;60(8):2280–2286. doi: 10.1007/s10620-015-3642-8.
    1. Moran N, Jones E, O'Toole A, Murray F. The appropriateness of a proton pump inhibitor prescription. Ir Med J. 2014;107(10):326–327.
    1. Haastrup P, Paulsen MS, Begtrup LM, Hansen JM, Jarbøl DE. Strategies for discontinuation of proton pump inhibitors: a systematic review. Fam Pract. 2014;31(6):625–630. doi: 10.1093/fampra/cmu050.
    1. Reeve E, Andrews JM, Wiese MD, Hendrix I, Roberts MS, Shakib S. Feasibility of a patient-centered deprescribing process to reduce inappropriate use of proton pump inhibitors. Ann Pharmacother. 2015;49(1):29–38. doi: 10.1177/1060028014558290.
    1. Lapane KL, Hughes CM. Optimising drug utilisation in long term care. Pharmacoeconomics. 2002;20(3):143–152. doi: 10.2165/00019053-200220030-00001.
    1. Labelle M, Beaulieu M, Paquette D, Fournier C, Bessette L, Choquette D, et al. An integrated approach to improving appropriate use of anti-inflammatory medication in the treatment of osteoarthritis in Québec (Canada): the CURATA model. Med Teach. 2004;26(5):463–470. doi: 10.1080/0142159042000218669.
    1. Dreischulte T, Grant A, Donnan P, McCowan C, Davey P, Petrie D, et al. A cluster randomised stepped wedge trial to evaluate the effectiveness of a multifaceted information technology-based intervention in reducing high-risk prescribing of non-steroidal anti-inflammatory drugs and antiplatelets in primary medical care: the DQIP study protocol. Implement Sci. 2012;7:24. doi: 10.1186/1748-5908-7-24.

Source: PubMed

Patrocinadores y Colaboradores

Condiciones médicas

Intervenciones de drogas

3
Suscribir