Advertisement

Prevalence and follow-up of potentially inappropriate medication and potentially omitted medication in older patients with cancer – The PIM POM study

  • Author Footnotes
    1 Both authors contributed equally to this manuscript
    Fianne M.A.M. van Loveren
    Footnotes
    1 Both authors contributed equally to this manuscript
    Affiliations
    Department of Clinical Pharmacy, Deventer Hospital, Nico Bolkesteinlaan 75, 7416 SE Deventer, the Netherlands
    Search for articles by this author
  • Author Footnotes
    1 Both authors contributed equally to this manuscript
    Inge R.F. van Berlo - van de Laar
    Correspondence
    Corresponding author at: Department of Clinical Pharmacy, Deventer Hospital, Nico Bolkesteinlaan 75, 7416 SE Deventer, the Netherlands.
    Footnotes
    1 Both authors contributed equally to this manuscript
    Affiliations
    Department of Clinical Pharmacy, Deventer Hospital, Nico Bolkesteinlaan 75, 7416 SE Deventer, the Netherlands
    Search for articles by this author
  • Alex L.T. Imholz
    Affiliations
    Department of Medical Oncology, Deventer Hospital, Nico Bolkesteinlaan 75, 7416 SE Deventer, the Netherlands
    Search for articles by this author
  • Esther van ’t Riet
    Affiliations
    Department of Research & Development, Nico Bolkesteinlaan 75, 7416 SE, Deventer Hospital, Deventer, the Netherlands
    Search for articles by this author
  • Katja Taxis
    Affiliations
    PharmacoTherapy, -Epidemiology and -Economics – Groningen Research, Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, the Netherlands
    Search for articles by this author
  • Frank G.A. Jansman
    Affiliations
    Department of Clinical Pharmacy, Deventer Hospital, Nico Bolkesteinlaan 75, 7416 SE Deventer, the Netherlands

    PharmacoTherapy, -Epidemiology and -Economics – Groningen Research, Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, the Netherlands
    Search for articles by this author
  • Author Footnotes
    1 Both authors contributed equally to this manuscript
Open AccessPublished:July 06, 2020DOI:https://doi.org/10.1016/j.jgo.2020.06.014

      Highlights

      • 78% of older patients with cancer have potentially inappropriate/omitted medication
      • A comprehensive pharmacist-led medication review can optimize patients' treatment
      • Follow-up on recommendations from these medication reviews is high (73%)
      • Pharmacists' expert opinion contributes significantly to STOPP/START criteria

      Abstract

      Objectives

      To determine the prevalence of Potentially Inappropriate Medication (PIMs) and Potentially Omitted Medication (POMs) in older patients with cancer.

      Materials and Methods

      In this prospective observational study (hospital) pharmacists conducted comprehensive medication reviews in older patients with cancer (aged ≥65 years) receiving parenteral chemotherapy and/or immunotherapy at the Deventer Hospital. PIMs and POMs were identified using the Screening Tool of Older Persons' potentially inappropriate Prescriptions (STOPP), the Screening Tool to Alert doctors to the Right Treatment (START), and pharmacists' expert opinion. Recommendations regarding PIMs and POMs were communicated to the patient's oncologist/haematologist and follow-up was measured. Associations between covariates and the prevalence of PIMs and POMs were statistically analysed.

      Results

      For the 150 patients included, 180 PIMs and 86 POMs were identified with a prevalence of 78%. Using pharmacists' expert opinion in addition to only STOPP/START criteria contributed to 49% of the PIMs and 23% of the POMs. A follow-up action was required in 73% of the 266 PIMs and POMs. Number of medicines and Charlson Comorbidity Index score were both associated with having at least one PIM and/or POM (p = .031 and p = .016, respectively).

      Conclusion

      The prevalence of PIMs and POMs and subsequent follow-up in older patients with cancer is high. A pharmacist-led comprehensive medication review is a good instrument to identify these PIMs and POMs and to optimize patients' treatment. A complete approach, including pharmacists' expert opinion, is recommended to identify all PIMs and POMs in clinical practice.

      Keywords

      1. Introduction

      Ageing, multiple morbidities, and the use of multiple medicines make older patients a high-risk group for drug-related problems (DRPs). The diagnosis of cancer further increases this risk. Cancer treatment leads to the use of more medicines, multiple involved health care providers, and a higher disease burden. Frequent hospital visits and the associated transfer of information about medication use are additional risk factors for DRPs, which can lead to compromised cancer management plans. Since this population will continue to grow, addressing the appropriateness of medication use in this population will become even more important [
      • Hamaker M.E.
      • Jonker J.M.
      • De Rooij S.E.
      • Vos A.G.
      • Smorenburg C.H.
      • Van Munster B.C.
      Frailty screening methods for predicting outcome of a comprehensive geriatric assessment in elderly patients with cancer: a systematic review.
      ,
      • Sharma M.
      • Loh K.P.
      • Nightingale G.
      • Mohile S.G.
      • Holmes H.M.
      Polypharmacy and potentially inappropriate medication use in geriatric oncology.
      ,
      • Nightingale G.
      • Hajjar E.
      • Swartz K.
      • Andrel-Sendecki J.
      • Chapman A.
      Evaluation of a pharmacist-led medication assessment used to identify prevalence of and associations with polypharmacy and potentially inappropriate medication use among ambulatory senior adults with cancer.
      ,
      • Deliens C.
      • Deliens G.
      • Filleul O.
      • Pepersack T.
      • Awada A.
      • Piccart M.
      • et al.
      Drugs prescribed for patients hospitalized in a geriatric oncology unit: potentially inappropriate medications and impact of a clinical pharmacist.
      ,
      • Paksoy C.
      • Özkan Ö.
      • Ustaalioğlu B.B.
      • Sancar M.
      • Demirtunç R.
      • Izzettin F.V.
      • et al.
      Evaluation of potentially inappropriate medication utilization in elderly patients with cancer at outpatient oncology unit.
      ].
      Several studies show that pharmacists, in a multidisciplinary approach, can play an important role in reducing DRPs by conducting medication reviews [
      • Chau S.H.
      • Jansen A.P.
      • Van de Ven P.M.
      • Hoogland P.
      • Elders P.J.
      • Hugtenburg J.G.
      Clinical medication reviews in elderly patients with polypharmacy: a cross-sectional study on drug-related problems in the Netherlands.
      ,
      • Tjia J.
      • Velten S.J.
      • Parsons C.
      • Valluri S.
      • Briesacher B.A.
      Studies to reduce unnecessary medication use in frail older adults: a systematic review.
      ,
      • Patterson S.M.
      • Cadogan C.A.
      • Kerse N.
      • Cardwell C.R.
      • Bradley M.C.
      • Ryan C.
      • et al.
      Interventions to improve the appropriate use of polypharmacy for older people.
      ,
      • Onder G.
      • Van der Cammen T.J.
      • Petrovic M.
      • Somers A.
      • Rajkumar C.
      Strategies to reduce the risk of iatrogenic illness in complex older adults.
      ]. Different criteria are used to identify Potentially Inappropriate Medications (PIMs) and Potentially Omitted Medications (POMs). Potentially Inappropriate Medications are defined as medicines that are used by a patient, but are either unnecessary or do not have additional value, or can be optimized in their use. Potentially Omitted Medications refer to medicines that are not used by a patient, but adding them is clinically indicated and can be beneficial for the patient. In Europe, the Screening Tool of Older Persons' potentially inappropriate Prescriptions (STOPP) and the Screening Tool to Alert doctors to the Right Treatment (START) are most recommended to identify PIMs and POMs [
      • Hill-Taylor B.
      • Sketris I.
      • Hayden J.
      • Byrne S.
      • O’Sullivan D.
      • Christie R.
      Application of the STOPP/START criteria: a systematic review of the prevalence of potentially inappropriate prescribing in older adults, and evidence of clinical, humanistic and economic impact.
      ]. However, using only these criteria does not lead to identification of all relevant PIMs and POMs and therefore a more comprehensive medication assessment is needed [
      • Sharma M.
      • Loh K.P.
      • Nightingale G.
      • Mohile S.G.
      • Holmes H.M.
      Polypharmacy and potentially inappropriate medication use in geriatric oncology.
      ,
      • Verdoorn S.
      • Kwint H.F.
      • Faber A.
      • Gussekloo J.
      • Bouvy M.L.
      Majority of drug-related problems identified during medication review are not associated with STOPP/START criteria.
      ].
      The Dutch multidisciplinary guideline ‘polypharmacy in the elderly’ recommends comprehensive medication reviews in patients aged ≥65 years with polypharmacy and having at least one predefined risk factor [
      • Dutch College of General Practitioners
      Multidisciplinary guideline ‘polypharmacy in the elderly’ 2012.
      ]. Oncology is not mentioned as a specific risk factor in this guideline and no Dutch study was found investigating PIMs and POMs and the impact of pharmacist-led comprehensive medication reviews in this population. In general, studies on the prevalence of PIMs and POMs in older patients with cancer have various limitations and methods and results differ highly [
      • Nightingale G.
      • Hajjar E.
      • Swartz K.
      • Andrel-Sendecki J.
      • Chapman A.
      Evaluation of a pharmacist-led medication assessment used to identify prevalence of and associations with polypharmacy and potentially inappropriate medication use among ambulatory senior adults with cancer.
      ,
      • Deliens C.
      • Deliens G.
      • Filleul O.
      • Pepersack T.
      • Awada A.
      • Piccart M.
      • et al.
      Drugs prescribed for patients hospitalized in a geriatric oncology unit: potentially inappropriate medications and impact of a clinical pharmacist.
      ,
      • Paksoy C.
      • Özkan Ö.
      • Ustaalioğlu B.B.
      • Sancar M.
      • Demirtunç R.
      • Izzettin F.V.
      • et al.
      Evaluation of potentially inappropriate medication utilization in elderly patients with cancer at outpatient oncology unit.
      ,
      • Prithviraj G.K.
      • Koroukian S.
      • Margevicius S.
      • Berger N.A.
      • Bagai R.
      • Owusu C.
      Patient characteristics associated with polypharmacy and inappropriate prescribing of medications among older adults with cancer.
      ,
      • Feng X.
      • Higa G.M.
      • Safarudin F.
      • Sambamoorthi U.
      • Tan X.
      Potentially inappropriate medication use and associated healthcare utilization and costs among older adults with colorectal, breast, and prostate cancers.
      ,
      • Karuturi M.S.
      • Holmes H.M.
      • Lei X.
      • Johnson M.
      • Barcenas C.H.
      • Cantor S.B.
      • et al.
      Potentially inappropriate medications defined by STOPP criteria in older patients with breast and colorectal cancer.
      ,
      • Saarelainen L.K.
      • Turner J.P.
      • Shakib S.
      • Singhal N.
      • Hogan-Doran J.
      • Prowse R.
      • et al.
      Potentially inappropriate medication use in older people with cancer: prevalence and correlates.
      ,
      • Reis C.M.
      • Dos Santos A.G.
      • De Jesus Souza P.
      • Reis A.M.M.
      Factors associated with the use of potentially inappropriate medications by older adults with cancer.
      ].
      Therefore, this study aims to determine the prevalence of PIMs and POMs in older patients with cancer by conducting pharmacist-led comprehensive medication reviews. Secondary objectives are to examine subtypes of PIMs and POMs, to determine follow-up of PIMs and POMs, and to assess risk factors for PIMs and POMs.

      2. Materials and Methods

      In this prospective observational study, pharmacist-led comprehensive medication reviews were conducted in a multidisciplinary team with older patients with cancer between May 2018 and January 2019 at the Deventer Hospital (a middle-sized teaching hospital in The Netherlands). Patients aged ≥65 years, treated for cancer by a medical oncologist/haematologist, and receiving parenteral chemotherapy and/or immunotherapy at the day care unit were enrolled in this study. Patients at the start of therapy as well as patients who already started therapy were included.
      Patients were asked to bring all their medication or a medication overview to the day care unit. While receiving chemotherapy or immunotherapy, a pharmacist or pharmacist in training interviewed the patient. The actual medication use, including non-prescription medicines, was verified with the patient (medication reconciliation) and problems with usage of medication were addressed using a questionnaire. Based on this information and the patient's medical records, PIMs and POMs were identified by the pharmacist using the revised STOPP/START criteria (2015) [
      • Knol W.
      • Verduijn M.M.
      • Lelie-Van der Zande A.C.
      • Van Marum R.J.
      • Brouwers J.R.
      • Van der Cammen T.J.
      • et al.
      Detecting inappropriate medication in older people: the revised STOPP/START criteria.
      ] and pharmacists' expert opinion. Expert opinion consisted of interpretation of medication surveillance signals, practical recommendations, and guideline adherence. Reviewing medication surveillance signals generated from the pharmacy information system is standard practice in Dutch hospital pharmacies. The pharmacists' expert opinion was part of the typical work and knowledge of a hospital pharmacist responsible for medication reconciliation and medication review. No specific framework, process, or list was used for the pharmacists' expert opinion. All identified PIMs and POMs and their corresponding recommendations were double-checked and if necessary complemented by a hospital pharmacist before communicating them to the patient's oncologist/haematologist. If there were discrepancies between the pharmacist and hospital pharmacist, the PIMs and POMs and their corresponding recommendations were based on consensus between the two. For each PIM/POM the oncologist/haematologist decided if a follow-up action was required. Two follow-up actions were possible: the recommendation was implemented by the oncologist/haematologist or the PIM/POM with corresponding recommendation was sent to the patient's general practitioner.
      The prevalence of PIMs and POMs (percentage of patients with at least one PIM and/or POM) was determined for PIMs and POMs combined as well as separately. PIMs and POMs were further classified by the Anatomical Therapeutic Chemical (ATC) classification, by the classification used in the STOPP/START criteria, and by the classification used in the Systematic Tool to Reduce Inappropriate Prescribing (STRIP) method [
      • Dutch College of General Practitioners
      Multidisciplinary guideline ‘polypharmacy in the elderly’ 2012.
      ,
      • Knol W.
      • Verduijn M.M.
      • Lelie-Van der Zande A.C.
      • Van Marum R.J.
      • Brouwers J.R.
      • Van der Cammen T.J.
      • et al.
      Detecting inappropriate medication in older people: the revised STOPP/START criteria.
      ,
      WHO Collaborating Centre for Drug Statistics Methodology
      ATC/DDD Index 2019.
      ].
      To determine the association of covariates with the prevalence of PIMs and POMs, the following information was collected for each patient: age, gender, number of different medicines, polypharmacy, use of a medication roll (medication pre-packaged per intake moment), cancer type, curative intent, and the Charlson Comorbidity Index (CCI) score. The number of different medicines included all medication used at home at the time of the interview, as well as the chemotherapy and/or immunotherapy, and accompanying supportive care agents. Polypharmacy was defined as concurrent use of five or more medicines for chronic use with a different ATC classification on ATC3-level, excluding medicines for dermal use (definition by the Dutch guideline ‘polypharmacy in the elderly’ [
      • Dutch College of General Practitioners
      Multidisciplinary guideline ‘polypharmacy in the elderly’ 2012.
      ]). Use of a medication roll was included as a measure for “self-management”. The patient's oncologist/haematologist indicated whether the cancer treatment was intended to be curative or not. Finally, the CCI score, determined by the classic scoring index by Charlson et al. [
      • Charlson M.E.
      • Pompei P.
      • Ales K.L.
      • MacKenzie C.R.
      A new method of classifying prognostic comorbidity in longitudinal studies: development and validation.
      ], was included as a measure for vulnerability and was based on the patient's medical records.
      Differences in these covariates for patients with and without PIMs/POMs were assessed using descriptive statistics (independent-samples t-test, Mann-Whitney U Test, Pearson's χ2 test, or Fisher's exact test). For factors significantly associated with the prevalence of PIMs and POMs (p-value <.05), univariate logistic regression followed by multivariate logistic regression was used to assess odds ratios (ORs) and 95% confidence intervals (CIs).
      This study was assessed and approved by the Medical Ethics Committee of Isala Hospital as a non-interventional study. All patients signed a written consent form prior to participating in this study.

      3. Results

      For this study, 159 patients were approached to participate of which four patients refused participation and five patients had their appointment rescheduled until after the research period. The patients' characteristics of the 150 patients included in this study are depicted in Table 1. In total, these patients used 1656 medicines, with a mean of eleven medicines per patient (range 3–21). One hundred and forty-four patients (96%) used five or more medicines and 99 patients (66%) used ten or more medicines. When excluding the chemotherapy and/or immunotherapy regimen and accompanying supportive care agents at the day care unit, the mean number of medicines per patient was seven with 77% and 23% of the patients using five or more and ten or more medicines, respectively.
      Table 1Patient characteristics.
      n = 150
      Age, years (median (IQR) [range])72 (8) [65–90]
      Gender (n (%))
       Male88 (59)
       Female62 (41)
      Number of medicines (mean (SD) [range])11.0 (3.8) [3–21]
      Number of medicines without chemotherapy, immunotherapy and supportive care agents (mean (SD) [range])7.2 (3.6) [0–17]
      Polypharmacy
      Chronic use of ≥5 different medicines, excl. Dermal use.
      (n (%))
       Yes91 (61)
       No59 (39)
      Medication roll (n (%))
       Yes18 (12)
       No132 (88)
      Cancer type (n (%))
       Solid tumours102 (68)
       Haematologic malignancies48 (32)
      Curative intent (n (%))
       Yes34 (23)
       No116 (77)
      CCI score (median (IQR) [range])4 (1) [3–9]
      Abbreviations: CCI, Charlson Comorbidity Index; IQR, interquartile range; SD, standard deviation.
      a Chronic use of ≥5 different medicines, excl. Dermal use.
      A total of 180 PIMs and 86 POMs were identified. These 266 PIMs and POMs give a mean of 1.8 per patient (range 0–8). PIMs and POMs were prevalent in 117 (78%) of the patients. The prevalence of PIMs and POMs separately was 65% and 46%, respectively (Fig. 1).
      Fig. 1
      Fig. 1– Prevalence of PIMs and POMs.
      The number of patients with no, 1, 2, 3, or ≥ 4 PIMs (separately), POMs (separately), and PIMs and/or POMs (combined). Percentages are calculated as part of the total (n = 150) per category. Abbreviations: PIM, Potentially Inappropriate Medication; POM, Potentially Omitted Medication. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
      Based on the ATC classification, the most common groups of medication for the 180 PIMs were proton pump inhibitors (PPIs) (19%), antihypertensive drugs (11%), benzodiazepine agonists (9%), analgesics (8%), alpha-adrenoreceptor antagonists (6%), and antidepressants (6%). Four PIMs (2%) concerned antineoplastic agents. The most common groups of medication for the 86 POMs were statins (40%), antihypertensive drugs (19%), and vitamin D (15%). Table 2 specifies the criteria used for identification of the PIMs and POMs.
      Table 2Criteria used for identification of PIMs and POMs.
      CriteriaClassificationn (%)
      PIMs186 (100)
      The total number of criteria used for identification of PIMs (186) exceeds the total number of PIMs (180) because 6 PIMs were identified using two criteria.
       STOPP criteriaTotal95 (51)
      A1. No evidence-based indication42 (23)
      A2. Usage longer than recommended25 (13)
      A3. Double medication8 (4)
      D5. Benzodiazepine ≥4 weeks12 (6)
      Other8 (4)
       Expert opinionTotal91 (49)
      Medicine not effective24 (13)
      Over treatment15 (8)
      (Potential) side effect9 (5)
      Contraindication or interaction2 (1)
      Incorrect dosage15 (8)
      Problem with usage26 (14)
      POMs86 (100)
       START criteriaTotal66 (77)
      B4. Antihypertensives, high BP7 (8)
      B5. Statins, high cardiovascular risk30 (35)
      H2. Bisph/vitD/calc, chronic prednisone use10 (12)
      H3. VitD/calc, osteoporosis6 (7)
      H5. VitD/calc, home bound / fall incidents4 (5)
      J2. ACE-inhibitor, DM with kidney damage5 (6)
      Other4 (5)
       Expert opinionTotal20 (23)
      Under treatment20 (23)
      Abbreviations: ACE, angiotensin converting enzyme; bisph, bisphosphonate; BP, blood pressure; calc, calcium; DM, diabetes mellitus; PIM, potentially inappropriate medication; POM, potentially omitted medication; START, screening tool to alert doctors to the right treatment; STOPP, screening tool of older persons' potentially inappropriate prescriptions; vitD, vitamin D.
      a The total number of criteria used for identification of PIMs (186) exceeds the total number of PIMs (180) because 6 PIMs were identified using two criteria.
      For 195 (73%) of the 266 identified PIMs and POMs a follow-up action was required according to the oncologist/haematologist. PIMs required more frequently a follow-up action than POMs, 76% vs 67% respectively. For 39% of the PIMs and POMs requiring a follow-up action, this action was realized by the oncologist/haematologist. The distribution of follow-up actions is summarized in Fig. 2.
      Fig. 2
      Fig. 2– Follow-up actions of PIMs and POMs.
      Follow-up actions of 180 PIMs (separately), 86 POMs (separately), and 266 PIMs and POMs (combined). Percentages are calculated as part of the total per category.Abbreviations: PIM, Potentially iIappropriate Medication; POM, Potentially Omitted Medication. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
      PIMs and POMs with a follow-up action realized by the oncologist/haematologist predominantly concerned PPIs (PIMs), anti-infectives (PIMs), antineoplastic agents (PIMs), musculoskeletal medication (PIMs/POMs), and vitamin D (POMs). Potentially Inappropriate Medications and Potentially Omitted Medicationss that were sent most frequently to the general practitioner were alpha-adrenoreceptor antagonists (PIMs), respiratory medication (PIMs), antihypertensive drugs (PIMs/POMs), and statins (POMs). PIMs identified with STOPP criterion A3 ‘double medication’ or expert opinion ‘contraindication or interaction’ were always considered as requiring a follow-up action. Follow-up was also high for expert opinion ‘incorrect dosage’ and ‘problem with usage’ with a follow-up action required for 87% and 86% of the PIMs, respectively. Follow-up was the lowest for START criterion B5 ‘statins for patients with high cardiovascular risk’ with no follow-up action required for 43% of the POMs.
      The number of medicines and the CCI score were associated with having at least one PIM and/or POM (Table 3). The other covariates were not statistically significant associated with the prevalence of PIMs and POMs. For an increase of one medicine, the odds of having at least one PIM and/or POM increased with 1.125. For an increase of one point in the CCI score, the odds of having at least one PIM and/or POM increased with 1.501. In multivariate logistic regression analysis both associations were no longer statistically significant. The Pearson correlation coefficient between the variables number of medicines and CCI score was 0.4.
      Table 3Associations between covariates and prevalence of PIMs and POMs.
      CovariateDescriptive statisticsLogistic regression
      No PIMs/POMsAny PIMs/POMs
      This group consists of all patients who have at least one PIM and/or POM.
      p-valueUnivariate analysis

      OR (95% CI)
      Multivariate analysis

      OR (95% CI)
      Total (n (%))33 (100)117 (100)
      Age, years (median (IQR))71 (7)73 (9)0.059
      Mann-Whitney U Test
      Gender, male (n (%))21 (64)67 (57)0.512
      Pearson's χ2 test
      Number of medicines (mean (SD))9.8 (4.0)11.4 (3.7)0.031
      independent-samples t-test
      1.125 (1.009–1.253)1.084 (0.963–1.221)
      Polypharmacy, yes (n (%))16 (48)75 (64)0.105
      Pearson's χ2 test
      Medication roll, yes (n (%))2 (6)16 (14)0.364
      Fisher's exact test.
      Cancer type, solid tumours (n (%))19 (58)83 (71)0.146
      Pearson's χ2 test
      Curative intent, yes (n (%))10 (30)24 (21)0.235
      Pearson's χ2 test
      CCI score (median (IQR))4 (2)4 (1)0.016
      Mann-Whitney U Test
      1.501 (1.043–2.160)1.360 (0.922–2.006)
      Abbreviations: CCI, Charlson Comorbidity Index; CI, confidence interval; IQR, interquartile range; OR, odds ratio; PIM, potentially inappropriate medication; POM, potentially omitted medication; SD, standard deviation.
      a This group consists of all patients who have at least one PIM and/or POM.
      b Mann-Whitney U Test
      c Pearson's χ2 test
      d independent-samples t-test
      e Fisher's exact test.

      4. Discussion

      A high prevalence of PIMs and POMs (78%) was found in older patients with cancer by conducting pharmacist-led comprehensive medication reviews using both STOPP/START criteria and pharmacists' expert opinion.
      The prevalence of PIMs in the current study is higher than in most previous studies. This might be due to a more thorough and complete approach for the comprehensive medication reviews. Most studies based their PIMs on the medical records rather than having an interview involving the patient. Furthermore, the current study used pharmacists' expert opinion in addition to the standardized STOPP/START criteria.
      Studies that did not include a patient interview and only used standardized criteria (Beers or STOPP) found a prevalence of PIMs ranging from 16% to 57% [
      • Paksoy C.
      • Özkan Ö.
      • Ustaalioğlu B.B.
      • Sancar M.
      • Demirtunç R.
      • Izzettin F.V.
      • et al.
      Evaluation of potentially inappropriate medication utilization in elderly patients with cancer at outpatient oncology unit.
      ,
      • Prithviraj G.K.
      • Koroukian S.
      • Margevicius S.
      • Berger N.A.
      • Bagai R.
      • Owusu C.
      Patient characteristics associated with polypharmacy and inappropriate prescribing of medications among older adults with cancer.
      ,
      • Feng X.
      • Higa G.M.
      • Safarudin F.
      • Sambamoorthi U.
      • Tan X.
      Potentially inappropriate medication use and associated healthcare utilization and costs among older adults with colorectal, breast, and prostate cancers.
      ,
      • Karuturi M.S.
      • Holmes H.M.
      • Lei X.
      • Johnson M.
      • Barcenas C.H.
      • Cantor S.B.
      • et al.
      Potentially inappropriate medications defined by STOPP criteria in older patients with breast and colorectal cancer.
      ,
      • Saarelainen L.K.
      • Turner J.P.
      • Shakib S.
      • Singhal N.
      • Hogan-Doran J.
      • Prowse R.
      • et al.
      Potentially inappropriate medication use in older people with cancer: prevalence and correlates.
      ]. Fourteen percent of the PIMs in the current study regarded problems with usage, most of which were identified based on the interview with the patient. These PIMs were missed in these previous studies. In addition, the medication reconciliation with the patient attributes to a more complete overview of the actual medication use and therefore to potentially more PIMs. Reis et al. [
      • Reis C.M.
      • Dos Santos A.G.
      • De Jesus Souza P.
      • Reis A.M.M.
      Factors associated with the use of potentially inappropriate medications by older adults with cancer.
      ], Nightingale et al. [
      • Nightingale G.
      • Hajjar E.
      • Swartz K.
      • Andrel-Sendecki J.
      • Chapman A.
      Evaluation of a pharmacist-led medication assessment used to identify prevalence of and associations with polypharmacy and potentially inappropriate medication use among ambulatory senior adults with cancer.
      ], and Deliens et al. [
      • Deliens C.
      • Deliens G.
      • Filleul O.
      • Pepersack T.
      • Awada A.
      • Piccart M.
      • et al.
      Drugs prescribed for patients hospitalized in a geriatric oncology unit: potentially inappropriate medications and impact of a clinical pharmacist.
      ] found a prevalence of 48%, 51%, and 52%, respectively, when interviewing the patient or conducting a full comprehensive medication review. However, not all PIMs and POMs can be identified with a set of standardized criteria and therefore the knowledge and expertise of a pharmacist is necessary to attribute to these criteria. This is well shown in this study where half of the PIMs and a quarter of the POMs were identified by pharmacists' expert opinion.
      To fully optimize patients' treatment, inappropriate medication should be addressed as well as omitted medication. Only two studies were found in which POMs were identified in older patients with cancer, with a prevalence of 34% and 98% [
      • Deliens C.
      • Deliens G.
      • Filleul O.
      • Pepersack T.
      • Awada A.
      • Piccart M.
      • et al.
      Drugs prescribed for patients hospitalized in a geriatric oncology unit: potentially inappropriate medications and impact of a clinical pharmacist.
      ,
      • Paksoy C.
      • Özkan Ö.
      • Ustaalioğlu B.B.
      • Sancar M.
      • Demirtunç R.
      • Izzettin F.V.
      • et al.
      Evaluation of potentially inappropriate medication utilization in elderly patients with cancer at outpatient oncology unit.
      ]. The high prevalence found by Paksoy et al. [
      • Paksoy C.
      • Özkan Ö.
      • Ustaalioğlu B.B.
      • Sancar M.
      • Demirtunç R.
      • Izzettin F.V.
      • et al.
      Evaluation of potentially inappropriate medication utilization in elderly patients with cancer at outpatient oncology unit.
      ] is largely attributed to omitted vaccinations, which is not applicable to the Dutch situation. In the Netherlands, older patients are annually offered an influenza vaccination and a pneumococcal vaccine is not included in the Dutch START criteria [
      • Knol W.
      • Verduijn M.M.
      • Lelie-Van der Zande A.C.
      • Van Marum R.J.
      • Brouwers J.R.
      • Van der Cammen T.J.
      • et al.
      Detecting inappropriate medication in older people: the revised STOPP/START criteria.
      ].
      The high prevalence of PIMs on PPIs and benzodiazepine agonists and POMs on statins, antihypertensive drugs, and vitamin D are in line with several other studies in patients with cancer as well as patients without cancer [
      • Deliens C.
      • Deliens G.
      • Filleul O.
      • Pepersack T.
      • Awada A.
      • Piccart M.
      • et al.
      Drugs prescribed for patients hospitalized in a geriatric oncology unit: potentially inappropriate medications and impact of a clinical pharmacist.
      ,
      • Chau S.H.
      • Jansen A.P.
      • Van de Ven P.M.
      • Hoogland P.
      • Elders P.J.
      • Hugtenburg J.G.
      Clinical medication reviews in elderly patients with polypharmacy: a cross-sectional study on drug-related problems in the Netherlands.
      ,
      • Saarelainen L.K.
      • Turner J.P.
      • Shakib S.
      • Singhal N.
      • Hogan-Doran J.
      • Prowse R.
      • et al.
      Potentially inappropriate medication use in older people with cancer: prevalence and correlates.
      ,
      • Reis C.M.
      • Dos Santos A.G.
      • De Jesus Souza P.
      • Reis A.M.M.
      Factors associated with the use of potentially inappropriate medications by older adults with cancer.
      ,
      • Bo M.
      • Gibello M.
      • Brunetti E.
      • Boietti E.
      • Sappa M.
      • Falcone Y.
      • et al.
      Prevalence and predictors of inappropriate prescribing according to the screening tool of older People’s prescriptions and screening tool to alert to right treatment version2 criteria in older patients discharged from geriatric and internal medicine wards: a prospective observational multicenter study.
      ,
      • Dalleur O.
      • Spinewine A.
      • Henrard S.
      • Losseau C.
      • Speybroeck N.
      • Boland B.
      Inappropriate prescribing and related hospital admissions in frail older persons according to the STOPP and START criteria.
      ]. Only four PIMs concerned antineoplastic drugs. Because most PIMs involved regular medication, the problems identified in the oncology population may not be much different from other populations of older polypharmacy patients and therefore STOPP/START criteria seem well applicable. Associations with the prevalence of PIMs and POMs were found for the number of medicines and the CCI score, in line with previous studies [
      • Nightingale G.
      • Hajjar E.
      • Swartz K.
      • Andrel-Sendecki J.
      • Chapman A.
      Evaluation of a pharmacist-led medication assessment used to identify prevalence of and associations with polypharmacy and potentially inappropriate medication use among ambulatory senior adults with cancer.
      ,
      • Paksoy C.
      • Özkan Ö.
      • Ustaalioğlu B.B.
      • Sancar M.
      • Demirtunç R.
      • Izzettin F.V.
      • et al.
      Evaluation of potentially inappropriate medication utilization in elderly patients with cancer at outpatient oncology unit.
      ,
      • Prithviraj G.K.
      • Koroukian S.
      • Margevicius S.
      • Berger N.A.
      • Bagai R.
      • Owusu C.
      Patient characteristics associated with polypharmacy and inappropriate prescribing of medications among older adults with cancer.
      ]. However, in this study these variables were not very strongly associated and borderline significant. The significant associations were no longer present in the multivariate logistic regression analysis possibly due to a lack of power and the mild correlation (Pearson correlation coefficient 0.4) between CCI score and number of medicines. Because of the time investment needed, implementation in daily practice can be challenging. This study indicates that a specific focus on patients with more medicines and/or a higher CCI score could be considered. However, ORs were small, associations were not statistically significant in multivariate logistic regression analysis, and this study was not designed to determine which (sub)group of patients would benefit most from pharmacist-led comprehensive medication reviews. Future research could provide more insight on this subject.
      Measuring follow-up further distinguishes this study from previous studies on PIMs and POMs in older patients with cancer. It was outside the scope of this study to assess actual changes in medication, additional laboratory measurements, or actions by the general practitioner, which could lead to an overestimation of the follow-up on PIMs and POMs. However, the follow-up percentage found in this study (73%) is in line with other studies that found action to be taken in 69%–82% of recommendations made by pharmacists [
      • Chau S.H.
      • Jansen A.P.
      • Van de Ven P.M.
      • Hoogland P.
      • Elders P.J.
      • Hugtenburg J.G.
      Clinical medication reviews in elderly patients with polypharmacy: a cross-sectional study on drug-related problems in the Netherlands.
      ,
      • Krska J.
      • Cromarty J.A.
      • Arris F.
      • Jamieson D.
      • Hansford D.
      • Duffus P.R.
      • et al.
      Pharmacist-led medication review in patients over 65: a randomized, controlled trial in primary care.
      ,
      • Gillespie U.
      • Alassaad A.
      • Henrohn D.
      • Garmo H.
      • Hammarlund-Udenaes M.
      • Toss H.
      • et al.
      A comprehensive pharmacist intervention to reduce morbidity in patients 80 years or older: a randomized controlled trial.
      ]. For all STOPP/START criteria, a follow-up action was required for the majority of PIMs and POMs. Even for criteria that might seem less relevant in older patients with cancer (for example starting statins or vitamin D + calcium), more than half of the POMs required a follow-up action and were therefore considered clinically relevant by the oncologist/haematologist. This shows that the criteria, which were used, are relevant to this patient population.
      Strengths of this study are the combination of a pharmacist-led comprehensive medication review and medication reconciliation with the patient, the incorporation of pharmacists' expert opinion, the identification of PIMs as well as POMs, and measuring the follow-up of recommendations. Limitations are that this is a single-institution study and only patients who received parenteral chemotherapy and/or immunotherapy were included. In addition, only the prevalence of PIMs and POMs was measured with the immediate follow-up, so long-term outcomes for patient and healthcare cannot be assessed.
      In conclusion, PIMs and POMs are highly prevalent among older patients with cancer and a pharmacist-led comprehensive medication reviews is a good instrument to optimize patients' treatment. A complete approach, including pharmacists' expert opinion, is recommended to identify all PIMs and POMs.

      Author Contributions

      Conception and Design: FMAM van Loveren, IRF van Berlo – van de Laar, ALT Imholz, E van 't Riet, K Taxis, FGA Jansman.
      Data Collection: FMAM van Loveren.
      Analysis and Interpretation of Data: FMAM van Loveren, IRF van Berlo – van de Laar, E van 't Riet.
      Manuscript Writing: FMAM van Loveren, IRF van Berlo – van de Laar.
      Approval of Final Article: FMAM van Loveren, IRF van Berlo – van de Laar, ALT Imholz, E van 't Riet, K Taxis, FGA Jansman.

      Disclosure

      None.

      Declaration of Competing Interest

      None.

      Acknowledgements

      The authors thank pharmacists in training Carlijn van der Velde and Marjolein Niewenhuijse for their contribution to the comprehensive medication reviews and data collection.

      References

        • Hamaker M.E.
        • Jonker J.M.
        • De Rooij S.E.
        • Vos A.G.
        • Smorenburg C.H.
        • Van Munster B.C.
        Frailty screening methods for predicting outcome of a comprehensive geriatric assessment in elderly patients with cancer: a systematic review.
        Lancet Oncol. 2012; 13 (e437-e44)
        • Sharma M.
        • Loh K.P.
        • Nightingale G.
        • Mohile S.G.
        • Holmes H.M.
        Polypharmacy and potentially inappropriate medication use in geriatric oncology.
        J Geriatr Oncol. 2016; 7: 346-353
        • Nightingale G.
        • Hajjar E.
        • Swartz K.
        • Andrel-Sendecki J.
        • Chapman A.
        Evaluation of a pharmacist-led medication assessment used to identify prevalence of and associations with polypharmacy and potentially inappropriate medication use among ambulatory senior adults with cancer.
        J Clin Oncol. 2015; 33: 1453-1459
        • Deliens C.
        • Deliens G.
        • Filleul O.
        • Pepersack T.
        • Awada A.
        • Piccart M.
        • et al.
        Drugs prescribed for patients hospitalized in a geriatric oncology unit: potentially inappropriate medications and impact of a clinical pharmacist.
        J Geriatr Oncol. 2016; 7: 463-470
        • Paksoy C.
        • Özkan Ö.
        • Ustaalioğlu B.B.
        • Sancar M.
        • Demirtunç R.
        • Izzettin F.V.
        • et al.
        Evaluation of potentially inappropriate medication utilization in elderly patients with cancer at outpatient oncology unit.
        J Oncol Pharm Pract. 2019; 25: 1321-1327
        • Chau S.H.
        • Jansen A.P.
        • Van de Ven P.M.
        • Hoogland P.
        • Elders P.J.
        • Hugtenburg J.G.
        Clinical medication reviews in elderly patients with polypharmacy: a cross-sectional study on drug-related problems in the Netherlands.
        Int J Clin Pharmacol. 2016; 38: 46-53
        • Tjia J.
        • Velten S.J.
        • Parsons C.
        • Valluri S.
        • Briesacher B.A.
        Studies to reduce unnecessary medication use in frail older adults: a systematic review.
        Drugs Aging. 2013; 30: 285-307
        • Patterson S.M.
        • Cadogan C.A.
        • Kerse N.
        • Cardwell C.R.
        • Bradley M.C.
        • Ryan C.
        • et al.
        Interventions to improve the appropriate use of polypharmacy for older people.
        Cochrane Database Syst Rev. 2014; : CD008165
        • Onder G.
        • Van der Cammen T.J.
        • Petrovic M.
        • Somers A.
        • Rajkumar C.
        Strategies to reduce the risk of iatrogenic illness in complex older adults.
        Age Ageing. 2013; 42: 284-291
        • Hill-Taylor B.
        • Sketris I.
        • Hayden J.
        • Byrne S.
        • O’Sullivan D.
        • Christie R.
        Application of the STOPP/START criteria: a systematic review of the prevalence of potentially inappropriate prescribing in older adults, and evidence of clinical, humanistic and economic impact.
        J Clin Pharm Ther. 2013; 38: 360-372
        • Verdoorn S.
        • Kwint H.F.
        • Faber A.
        • Gussekloo J.
        • Bouvy M.L.
        Majority of drug-related problems identified during medication review are not associated with STOPP/START criteria.
        Eur J Clin Pharmacol. 2015; 71: 1255-1262
        • Dutch College of General Practitioners
        Multidisciplinary guideline ‘polypharmacy in the elderly’ 2012.
        (Utrecht)2012
        • Prithviraj G.K.
        • Koroukian S.
        • Margevicius S.
        • Berger N.A.
        • Bagai R.
        • Owusu C.
        Patient characteristics associated with polypharmacy and inappropriate prescribing of medications among older adults with cancer.
        J Geriatr Oncol. 2012; 3: 228-237
        • Feng X.
        • Higa G.M.
        • Safarudin F.
        • Sambamoorthi U.
        • Tan X.
        Potentially inappropriate medication use and associated healthcare utilization and costs among older adults with colorectal, breast, and prostate cancers.
        J Geriatr Oncol. 2019; 10: 698-704
        • Karuturi M.S.
        • Holmes H.M.
        • Lei X.
        • Johnson M.
        • Barcenas C.H.
        • Cantor S.B.
        • et al.
        Potentially inappropriate medications defined by STOPP criteria in older patients with breast and colorectal cancer.
        J Geriatr Oncol. 2019; 10: 705-708
        • Saarelainen L.K.
        • Turner J.P.
        • Shakib S.
        • Singhal N.
        • Hogan-Doran J.
        • Prowse R.
        • et al.
        Potentially inappropriate medication use in older people with cancer: prevalence and correlates.
        J Geriatr Oncol. 2014; 5: 439-446
        • Reis C.M.
        • Dos Santos A.G.
        • De Jesus Souza P.
        • Reis A.M.M.
        Factors associated with the use of potentially inappropriate medications by older adults with cancer.
        J Geriatr Oncol. 2017; 8: 303-307
        • Knol W.
        • Verduijn M.M.
        • Lelie-Van der Zande A.C.
        • Van Marum R.J.
        • Brouwers J.R.
        • Van der Cammen T.J.
        • et al.
        Detecting inappropriate medication in older people: the revised STOPP/START criteria.
        Ned Tijdschr Geneeskd. 2015; 159: A8904
        • WHO Collaborating Centre for Drug Statistics Methodology
        ATC/DDD Index 2019.
        ([accessed 22 March 2019])
        • Charlson M.E.
        • Pompei P.
        • Ales K.L.
        • MacKenzie C.R.
        A new method of classifying prognostic comorbidity in longitudinal studies: development and validation.
        J Chronic Dis. 1987; 40: 373-383
        • Bo M.
        • Gibello M.
        • Brunetti E.
        • Boietti E.
        • Sappa M.
        • Falcone Y.
        • et al.
        Prevalence and predictors of inappropriate prescribing according to the screening tool of older People’s prescriptions and screening tool to alert to right treatment version2 criteria in older patients discharged from geriatric and internal medicine wards: a prospective observational multicenter study.
        Geriatr Gerontol Int. 2019; 19: 5-11
        • Dalleur O.
        • Spinewine A.
        • Henrard S.
        • Losseau C.
        • Speybroeck N.
        • Boland B.
        Inappropriate prescribing and related hospital admissions in frail older persons according to the STOPP and START criteria.
        Drugs Aging. 2012; 29: 829-837
        • Krska J.
        • Cromarty J.A.
        • Arris F.
        • Jamieson D.
        • Hansford D.
        • Duffus P.R.
        • et al.
        Pharmacist-led medication review in patients over 65: a randomized, controlled trial in primary care.
        Age Ageing. 2001; 30: 205-211
        • Gillespie U.
        • Alassaad A.
        • Henrohn D.
        • Garmo H.
        • Hammarlund-Udenaes M.
        • Toss H.
        • et al.
        A comprehensive pharmacist intervention to reduce morbidity in patients 80 years or older: a randomized controlled trial.
        Arch Intern Med. 2009; 169: 894-900