University of Groningen
Deprescribing in older people
van der Meer, Helene Grietje
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Publication date: 2019
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van der Meer, H. G. (2019). Deprescribing in older people: development and evaluation of complex healthcare interventions. Rijksuniversiteit Groningen.
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General introduction and thesis outline Deprescribing in older people
CHAPTER 7
7
General discussion
MAIN FINDINGS
This thesis addresses different stages in the process of develop-ing and evaluatdevelop-ing deprescribdevelop-ing interventions. Deprescribdevelop-ing interventions usually are complex, involving various stakehold-ers, such as doctors, pharmacists, patients and patients’ care-givers. The UK Medical Research Council (MRC) has published guidance regarding best practice for developing and evaluating complex healthcare interventions. [1] Thus, we positioned the chapters of this thesis in the context of the MRC guidance (Figure 1).
In the first part of this thesis, two methods for the identification of potentially inappropriate prescribing of specific medications within defined populations were explored. Using a retrospective cohort study we identified high use of preventive medications at the end of life in older nursing home residents. The study also highlights the use of routinely collected data for the identifica-tion of potentially inappropriate prescribing (Chapter 2). The study showed that deprescribing remained limited, with little change in medication prescribing throughout the last year of life. Small increases in the prescribing of symptomatic medications indicated some awareness of changed need, but high prescribing of preventive medications suggested treatment goals were not be-ing revised when life expectancy changed. Usbe-ing a cross-sectional study design in a national population of community-dwelling older persons, we identified individuals with a high anticholiner-gic/sedative load (Chapter 3). Our results showed that a large pro-portion of older community-dwelling patients in the Netherlands had a high anticholinergic/sedative medication load. According to their medication use, four distinct subpopulations with high anticholinergic/sedative loads were identified using latent class analysis. Both studies provide evidence for deprescribing oppor-tunities, and therefore are positioned in the development stage of the MRC development and evaluation process.
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General discussion Deprescribing in older people
While it is best practice to evaluate an intervention before im-plementing it in practice, sometimes interventions are imple-mented without first evaluating effectiveness. In this case, the effectiveness of the intervention might need to be evaluated in practice, for example in specific circumstances (defined target populations/specific medications). The deprescribing interven-tion, pharmacist-led medication review as currently performed in the Netherlands, was evaluated in a randomised controlled trial to examine its effectiveness on deprescribing chronically used an-ticholinergic/sedative medications in older community-dwelling patients with a high anticholinergic/sedative load. The results of this study showed that while vulnerable older people in need of medication optimisation were targeted, pharmacist-led medica-tion reviews were not effective in deprescribing anticholinergic/ sedative medications in this population (Chapter 4 and 5). This study showed the need to go back to the development and fea-sibility/piloting stage in order to target the intervention to this population. The study also suggests the need for de-implementa-tion of ineffective medicade-implementa-tion review activities in this populade-implementa-tion. Based on the results of Chapter 3, 4 and 5, a new deprescribing in-tervention was developed and its feasibility, acceptability and po-tential effectiveness were tested in a prospective study (Chapter 6). This study design was more sophisticated than a feasibility/pilot, but not yet a definite effectiveness evaluation (randomised con-trolled trial) and is therefore positioned between these two stages in the MRC development and evaluation process. The new depre-scribing intervention signalled initiation of a new anticholinergic/ sedative medication in older people with an already high anticho-linergic/sedative load. The results of the study showed that this intervention was feasible, as a considerable number of patients in need of medication optimisation could be identified. Acceptability of the intervention was high both among pharmacists and pa-tients and time investment was reasonable. Also, the intervention was potentially effective, as in one third of patients an increase in anticholinergic/sedative load was prevented.
WHAT CAN WE LEARN FROM THIS THESIS?
This thesis shows a robust approach of developing and evaluating deprescribing interventions, by performing a variety of studies investigating different stages in the process. All studies in this thesis focused on older people at high risk for medication related harm. Within each study, specific subpopulations of older people were targeted, such as nursing home residents at the end of life or community-dwelling older patients. Furthermore, different med-ication groups were studied (preventive medmed-ications, anticholin-ergic/sedative medications) using different study designs (retro-spective, cross-sectional, randomised controlled trial, feasibility/ acceptability/potential effectiveness study).
This thesis highlights that pharmacist-led medication review as currently conducted in the Netherlands is not a suitable interven-tion for deprescribing chronically used anticholinergic/sedative medications among older community-dwelling patients. While effectiveness of pharmacist-led medication review for optimising medication was found in other population groups, such as users of cardiovascular medication [2] and nursing home residents, [3] the lack of effectiveness of pharmacist-led medication review in our
Figure 1: Position of the studies described in this thesis in the figure ‘Key elements of the development and evaluation process’ by the UK Medical Research Council. Adapted by permission from BMJ Publishing Group Limited. Developing and evaluating complex interventions: the new Medical Research Council guidance, Craig P, Dieppe P, Macintyre S, et al., 337:a1655, ©2008.
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General discussion Deprescribing in older people
population may be due to a number of factors. Firstly, it may be related to differences in patient populations and risk assessment of their medications, e.g. long term risks for cognitive- and phys-ical decline in anticholinergic/sedative medications, [4, 5] which may be difficult to assess, versus measurable hard outcomes, such as blood pressure, for cardiovascular medication. [6] Secondly, differences in the level of collaboration between the pharmacist and physician. Close collaboration of physicians specialised in aged care with pharmacists in nursing homes, might have been accountable for the positive effects of medication review seen in this setting. [3] Several barriers to deprescribing have been iden-tified, including the collaboration between different health care professionals. [7] Based on our findings we would like to add an important barrier/enabler, which is targeting the deprescribing to the right subpopulation.
Considering these barriers, an innovative deprescribing inter-vention on anticholinergic/sedative medications was developed targeting newly initiated, instead of chronic, anticholinergic/ sedative medications. Evaluation of the intervention showed it was a feasible, acceptable and potentially effective approach to re-ducing anticholinergic/sedative load in older community-dwell-ing adults. The intervention targeted specific medications rather than all chronic anticholinergic/sedative medications, it was less time consuming than current medication review processes [8, 9] and the newly initiated anticholinergic/sedative medication and other anticholinergic/sedative medications were highlighted for the pharmacist when selecting a patient. Furthermore, guidance on prescribing of relevant anticholinergic/sedative medications was provided, helping the pharmacist to propose evidence-based recommendations for medication optimisation. While showing promise in terms of effectiveness, this study also suggests some refinements of the intervention, such as electronic integration of the intervention, including most updated evidence-based phar-macotherapeutic advice and a more specific focus on relevant medications. Furthermore, a complete overview of a patient’s
medication use and a good collaboration with the patient’s GP is needed. [10]
While for anticholinergic/sedative medications we developed and evaluated interventions, it was outside the scope of this thesis to perform this for preventive medications used at the end of life in older nursing home residents. Our study showed prescribing of preventive medication in this population is high, suggesting the potential need for deprescribing. Since the initiation of our study in 2013, several studies have been performed in this area, includ-ing an exploration of patients’, relatives’, nurses’ and physicians’ perspective on medication management at the end of life [11] and identification of barriers of physicians to deprescribe medications at the end of life. [12] An efficacy study on the use of antipsy-chotics for delirium in palliative care [13] indicates the growing awareness of the need for evidence-base prescribing in individu-als at the end of life. A first pragmatic trial showed positive effects of deprescribing statins at the end of life. [14] Suggestions were even made for best choices on study designs for the evaluation of deprescribing in an older population with limited life expectancy. [15] As highlighted already, multidisciplinary medication reviews have been found to be effective to discontinue inappropriate medication in nursing home residents. [3] This body of research is a good basis to develop specific interventions optimising med-ication use at the end of life in older people, following the MRC development and evaluation process.
IMPLICATIONS FOR PRACTICE AND FURTHER RESEARCH
Our studies support the concept of the development and eval-uation process of complex healthcare interventions following best practice guidance. [1] Good evidence on real world practice is required before implementing an intervention and scaling up. [16] Interventions that are implemented without evidence-based development and extensive evaluation can lead to ineffective
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General discussion Deprescribing in older people
clinical practice and unnecessary time- and financial investment. [17] The MRC framework provides useful guidance in the process of development and evaluation of interventions, but based on this thesis we would suggest an amendment to this process. The MRC process does not include the step from implementation back to evaluation, while this thesis shows that sometimes this step may be needed. Thus we propose the red arrow in Figure 1. If an al-ready implemented intervention is to be used for different medi-cations or population groups, it should be re-evaluated and if not effective, the intervention should not be used for this population. This may lead to de-implementation of the intervention. [18] Despite the extensive work in this thesis, a number of questions remain. Our study about preventive medication at the end of life raises the question about the timing of deprescribing. At which point do risks outweigh the benefits and when is a patient at his/her end of life? Our study on medication reviews leaves the question which patient population may benefit from medica-tion reviews. What is the best way to identify this patient group? Algorithms seem to be an efficient way to identify target popu-lations for an intervention. Furthermore, how do we know a pa-tient is benefiting from deprescribing? Robust meta-analyses have not been able to show significant effects of medication review on hard outcomes, such as hospitalisation and mortality. [19–22] Outcome reporting of studies evaluating medication review is heterogeneous. A core set of relevant patient outcomes, like geri-atric outcomes (e.g. fall risk, frailty and cognitive function) and adverse events (e.g. side effects, drug-related hospital admission) should be evaluated in real world randomised controlled trials. [23] Furthermore, cost-effectiveness evaluations should be per-formed to advise policy makers about potential implementation of interventions. [16] Interprofessional collaboration of health-care providers, such as pharmacists and general practitioners, but also medical specialists should be improved, as poorly developed interprofessional relationships are an important barrier in the de-prescribing process. [24] Improving pharmacists’ communication
skills might improve the interprofessional collaboration. [25] More specific guidelines are needed to help healthcare profes-sionals in the deprescribing process. The underlying pharma-cotherapeutic evidence remains weak, although some work has been done, e.g. the study about efficacy of antipsychotics for de-lirium in palliative care, described above. [13] Deprescribing in-terventions should be patient-centred and recommendations for deprescribing should be based on shared decision-making with the patient. [26] More work is needed to understand the patient perspective in this process. This may include helping patients understand the benefits of deprescribing medication and taking away their fears for adverse effects of deprescribing. [27]
CONCLUSIONS
Opportunities for deprescribing exist in older populations, such as the high prescribing of preventive medications at the end of life in older nursing home residents and anticholinergic/seda-tive medications in older community-dwelling adults. To reduce a high anticholinergic/sedative load in community- dwelling older adults, medication reviews, as currently performed in the Netherlands, are not effective. An innovative deprescribing in-tervention using information technology to target newly pre-scribed anticholinergic/sedative medication in this population seems more successful. Future deprescribing strategies should be patient- centred, targeted to the right populations and medica-tions, tailored to patient's needs, and should have a high degree of interprofessional collaboration.
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General discussion Deprescribing in older people
REFERENCES
1. Craig P, Dieppe P, Macintyre S, et al. Developing and evaluating complex interven-tions: the new Medical Research Council guidance. BMJ. 2008;337:a1655. 2. Jokanovic N, Tan EC, Sudhakaran S, et al. Pharmacist-led medication review in
com-munity settings: An overview of systematic reviews. Res Social Adm Pharm. 2017;13(4):661–685.
3. Wouters H, Scheper J, Koning H, et al. Discontinuing inappropriate medication use in nursing home residents: A cluster randomized controlled trial. Ann Intern Med. 2017;167(9):609–617.
4. Fox C, Smith T, Maidment I, et al. Effect of medications with anti-cholinergic prop-erties on cognitive function, delirium, physical function and mortality: a sys-tematic review. Age Ageing. 2014;43(5):604–615.
5. Park H, Satoh H, Miki A, Urushihara H, Sawada Y. Medications associated with falls in older people: systematic review of publications from a recent 5-year period. Eur J Clin Pharmacol. 2015;71(12):1429–1440.
6. Tan EC, Stewart K, Elliott RA, George J. Pharmacist services provided in general practice clinics: a systematic review and meta-analysis. Res Social Adm Pharm. 2014;10(4):608–622.
7. Anderson K, Stowasser D, Freeman C, Scott I. Prescriber barriers and enablers to minimising potentially inappropriate medications in adults: a systematic review and thematic synthesis. BMJ Open. 2014;4(12):e006544.
8. Willeboordse F, Schellevis FG, Meulendijk MC, Hugtenburg JG, Elders PJM. Imple-mentation fidelity of a clinical medication review intervention: process evalua-tion. Int J Clin Pharm. 2018;40(3):550–565.
9. Mast R, Schouten G, van Woerkom M. Niveau van medicatiebeoordeling initiatieven in Nederland kan beter. (Room for improvement in medication review initiatives in the
Netherlands). Pharmaceutisch Weekblad. 2010;4(11/12):189–194.
10. Kwint HF, Bermingham L, Faber A, Gussekloo J, Bouvy ML. The relationship be-tween the extent of collaboration of general practitioners and pharmacists and the implementation of recommendations arising from medication review: a sys-tematic review. Drugs Aging. 2013;30(2):91–102.
11. Dees MK, Geijteman ECT, Dekkers WJM, et al. Perspectives of patients, close rel-atives, nurses, and physicians on end-of-life medication management. Palliat Support Care. 2017 [Epub ahead of print].
12. Geijteman ECT, Huisman BAA, Dees MK, et al. Medication Discontinuation at the End of Life: A Questionnaire Study on Physicians’ Experiences and Opinions. J Palliat Med. 2018 [Epub ahead of print].
13. Agar MR, Lawlor PG, Quinn S, et al. Efficacy of Oral Risperidone, Haloperidol, or Placebo for Symptoms of Delirium Among Patients in Palliative Care: A Ran-domized Clinical Trial. JAMA Intern Med. 2017;177(1):34–42.
14. Kutner JS, Blatchford PJ, Taylor DH,Jr, et al. Safety and benefit of discontinuing sta-tin therapy in the setsta-ting of advanced, life-limista-ting illness: a randomized clinical trial. JAMA Intern Med. 2015;175(5):691–700.
15. Geijteman EC, Tiemeier H, van Gelder T. Selecting the Optimal Design for Drug Discontinuation Trials in a Setting of Advanced, Life-Limiting Illness. JAMA In-tern Med. 2015;175(10):1724–1725.
16. Guthrie B, Gillies J, Calderwood C, Smith G, Mercer S. Developing mid-dle-ground research to support primary care transformation. Br J Gen Pract. 2017;67(664):498–499.
17. Verkerk EW, Tanke MAC, Kool RB, van Dulmen SA, Westert GP. Limit, lean or lis-ten? A typology of low-value care that gives direction in de-implementation. Int J Qual Health Care. 2018 [Epub ahead of print].
18. Norton WE, Kennedy AE, Chambers DA. Studying de-implementation in health: an analysis of funded research grants. Implement Sci. 2017;12(1):144.
19. Wallerstedt SM, Kindblom JM, Nylen K, Samuelsson O, Strandell A. Medication re-views for nursing home residents to reduce mortality and hospitalization: sys-tematic review and meta-analysis. Br J Clin Pharmacol. 2014;78(3):488–497. 20. Holland R, Desborough J, Goodyer L, Hall S, Wright D, Loke YK. Does pharmacist-
led medication review help to reduce hospital admissions and deaths in older people? A systematic review and meta-analysis. Br J Clin Pharmacol. 2008;65(3):303–316.
21. Thomas R, Huntley AL, Mann M, et al. Pharmacist-led interventions to reduce un-planned admissions for older people: a systematic review and meta-analysis of randomised controlled trials. Age Ageing. 2014;43(2):174–187.
22. Hohl CM, Wickham ME, Sobolev B, et al. The effect of early in-hospital medi-cation review on health outcomes: a systematic review. Br J Clin Pharmacol. 2015;80(1):51–61.
23. Beuscart JB, Pont LG, Thevelin S, et al. A systematic review of the outcomes re-ported in trials of medication review in older patients: the need for a core out-come set. Br J Clin Pharmacol. 2017;83(5):942–952.
24. Anderson K, Foster M, Freeman C, Luetsch K, Scott I. Negotiating “Unmeasur-able Harm and Benefit”: Perspectives of General Practitioners and Consultant Pharmacists on Deprescribing in the Primary Care Setting. Qual Health Res. 2017;27(13):1936–1947.
25. Luetsch K, Rowett D. Developing interprofessional communication skills for phar-macists to improve their ability to collaborate with other professions. J Interprof Care. 2016;30(4):458–465.
26. Jansen J, Naganathan V, Carter SM, et al. Too much medicine in older people? De-prescribing through shared decision making. BMJ. 2016;353:i2893.
27. Reeve E, To J, Hendrix I, Shakib S, Roberts MS, Wiese MD. Patient barriers to and enablers of deprescribing: a systematic review. Drugs Aging. 2013;30(10):793–807.
