original articles
Annals of Oncology Annals of Oncology 25: 500–504, 2014 doi:10.1093/annonc/mdt553 Published online 9 January 2014
Is oral chemotherapy prescription safe for patients? A cross-sectional survey A. Bourmaud1,2*,†, C. Pacaut3,†, A. Melis3, F. Tinquaut1, N. Magné4,5, Y. Merrouche2,3 & F. Chauvin1,2,6 1 Department of Public Health, Hygée Centre, Lucien Neuwirth Cancer Institut, Saint Priest en Jarez; 2Therapeutic Targeting in Oncology, EMR3738, Claude Bernard University, Lyon; Departments of 3Medical Oncology; 4Radiotherapy, Lucien Neuwirth Cancer Institut, Saint Priest en Jarez; 5Cellular and Biomolecular Radiobiology, EMR3738, Claude Bernard University, Lyon; 6Clinical Investigation Center and Clinical Epidemiology, CIE 3, Jean Monnet University, Saint-Etienne, France
Received 5 July 2013; revised 7 October 2013 and 30 October 2013; accepted 18 November 2013
introduction More than 25% of the 400 antineoplastic agents currently being developed are oral drugs, most of them being targeted molecular drugs [1]. This move towards developing oral drugs is driven by the potential advantages that oral treatment can provide for patients. Oral administration increases the patients’ autonomy by reducing the number of hospital visits, which is all the more important when the treatment is long term [2]. However, these new oral drugs bring a new set of problems including the need to assess and improve patient’s adherence [3] and to develop information on the management of treatment-related adverse events in outpatients [1].
*Correspondence to: Dr Aurélie Bourmaud, Department of Public Health, Hygée Centre, Lucien Neuwirth Cancer Institut, 108 bis avenue A. Raimond, 42 270 Saint Priest en Jarez, France. Tel: +33-477-917-477; Fax: +33-477-917-497; E-mail: [email protected] †
Both authors contributed equally.
Certain categories of oral chemotherapies, such as cytotoxic chemotherapies or targeted therapies, have similar toxicities to their i.v. counterparts [1, 4–6]. However, the levels of safety and monitoring for oral chemotherapy administration are less rigorous than those for i.v. chemotherapy administration [4, 7]. Despite recent guidelines and updates to guidelines, implementation of these recommendations in clinical practices seems heterogeneous, insufficient and is considered to be a priority in this field [1, 3–5, 7–12]. To date, only a single study carried out in 42 American comprehensive cancer centres (CCCs) was carried out to characterise current safety practices and identify variation in these practices in 2007 [7]. This study demonstrated wide variations in prescription practices, in the monitoring of toxicity and in the educational advice given to the patients. No recent data are available as regard to these practices and these information may help in developing and implementing adequate prescription guidelines. The main objective of this study was to achieve an exhaustive collection of information on prescription practices, monitoring
© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].
Downloaded from http://annonc.oxfordjournals.org/ at University of Michigan on July 7, 2015
Background: Oral chemotherapies are increasingly prescribed. Yet wide variations in prescription practices and in monitoring of toxicity have been underlined despite existing guidelines. There is little recent information available as regard to these practices. We aimed to obtain exhaustive information on oral chemotherapy prescription practices and safety monitoring in French hospitals. Methods: A cross-sectional multicentre survey was carried out to collect information on drug prescription, administration and surveillance: prescribing practices, coordination and monitoring of adherence, safety monitoring and side-effects occurrence prevention. Participants were a large sample of the French oncologists prescribing oral chemotherapy (20%). Results: One hundred and fifty-seven oncologists from 112 hospitals ( public, comprehensive cancer centres and private) replied (23.7% of cancer hospitals). The majority (56.1%) of the prescriptions were hand-written on a blank sheet. Eighty-four physicians (53.5%) included dose information and 36 (23%) declared having no monitoring procedures for adherence. Only 84 responders (54%) provided education material at first prescription of oral chemotherapy in way to limit avoidable side-effects. Sixty-one (39%) responders stated that they recalled at least one serious adverse event in the previous year declared in their centre. Conclusions: In this 2012 study, the majority of prescribers followed no standards in prescription writing, safety monitoring and toxicity prevention. The implementation of the international recommendations for oral chemotherapy administration should be considered as a top priority—for both prescribers and health authorities—as regards to the dynamic of development of these molecules and their potential side-effects. Key words: oral chemotherapy, prescription practices, safety monitoring, side-effects prevention, patient adherence, education of patient
original articles
Annals of Oncology
and management of patients taking oral chemotherapy prescribed by oncologists in France. The secondary objectives were to compare prescribing practices and level of recollection of adverse events across centres.
methods We carried out a cross-sectional, prospective and multicentre study of French oncologists between January 2012 and April 2012. We targeted all active oncologists prescribing oral chemotherapy in public and private hospitals or in a CCC.
questionnaire
The responders’ characteristics were analysed descriptively by the frequency ( percentages). The association between the type of centre and the frequency of recollection of severe adverse events and prescription practices was explored using univariate analyses. Binomial, stepwise multivariate logistic regression analyses were carried out for the dependant variable ‘reporting of a severe adverse event’. Variables with a P < 0.20 in the univariate analyses were included in the multivariate analyses with a significance threshold of P < 0.05. All analyses, except the spatial analyses, were carried out using SAS (version 9.1).
results responses Overall, 260 oncologists were proposed this survey, and 157 questionnaires were completed (20.1% of the 780 French oncologists). These questionnaires came from 112 different centres in France, including the French overseas departments and territories, i.e. 23.7% of the 473 French hospitals authorised to prescribe chemotherapy [13]. Our survey covered 56 public hospitals (i.e. 23.6% of the French public hospitals including 77% of French teaching hospitals), 20 CCC (i.e. all the French centres) and 36 private hospitals (i.e. 17% of the private hospitals specialised in cancer). Supplementary Figure S1, available at Annals of Oncology online shows that the distribution of the responders throughout France was uniform. The responders (Table 1) practiced mostly in the public sector (45.2%), and they were more often experienced doctors (89.2% hospital physicians compared with 10.2% residents).
study protocol Oncologists were contacted by phone from January 2012 to April 2012 to obtain their answers to the questionnaire by Pacaut during office hours. Information on serious adverse events recollection was based on respondents’ reports. Serious adverse events were defined as events associated to oral chemotherapy and either (i) a grade 4 toxicity requiring hospitalisation; (ii) resulting in work incapacity or (iii) considered as life-threatening and reported accordingly. If the investigator remembered a declaration of serious adverse events in his centre for at least one patient in the previous year, the event was coded as being a recollection of a serious adverse event.
data collected The responses to the questionnaire provided a description of oncologists’ current practices. We analysed the response rates in terms of geographic distribution. We also analysed the responses by type hospital ( public, private or CCC) and tried to identify specific prescription practices that could be associated with a recollection of serious adverse event.
prescribing Oral chemotherapy prescribing practices were highly variable, as were the compulsory elements required for each prescription (Table 2). Fifty-six percent of responders still use handwritten prescriptions, while 38.9% report using electronic order entry systems. The inclusion of the compulsory requirements for the prescription of the six most commonly used oral chemotherapies was also highly variable; 53.5% of the clinicians provided information on the dose; 26.8% provided the calculation of the body surface area; and only 8.3% had the prescription verified by another clinician. Almost half (44.6%) of the clinicians
Table 1. Characteristics of the 157 clinicians who replied to the questionnaire Characteristics (N = 157)
sample selection All practicing physicians are registered with the French Medical Board; there were 780 medical oncologists practicing in France at the start of this study. Our goal was to interview 20% (156 of 780) of those registered in order to obtain a representative sample, to allow feasibility of this study and to obtain a sufficient precision as regard to the answers. Sample size was calculated before study to allow a 5%–10% precision in the answer related to recollection of adverse event. Assumptions were based on the Weingart et al. study [7]. To reach this objective, we carried out a computer-generated randomisation (without stratification) to select 260 of them (one-third).
Volume 25 | No. 2 | February 2014
Type of centre Public sector Comprehensive cancer centre Private sector Function Professor Senior Resident No answer
Responders, n (%) 71 (45.2) 49 (31.2) 37 (23.6) 9 (5.7) 131 (83.5) 16 (10.2) 1 (0.6)
doi:10.1093/annonc/mdt553 |
Downloaded from http://annonc.oxfordjournals.org/ at University of Michigan on July 7, 2015
We used a French translation of the questionnaire on prescription practices used in 2005 in the study of American CCCs [7]. We obtained permission from Dr Weingart to translate and use the questionnaire for the same objective of collecting data on prescription practices in France. Two oncologists and a physician–methodologist translated the questionnaire; the translated questionnaire was tested on five local oncologists and modified to integrate their comments to improve its clarity while respecting the initial text. The English version of this questionnaire can be found online (supplementary Appendix, available at Annals of Oncology online). The questionnaire examined prescribing practices, safety monitoring, coordination and monitoring of adherence and education of patients about oral chemotherapy. Oral chemotherapy was defined to respondents as ‘cytotoxic chemotherapies and targeted molecular therapies considered by the responding oncologist as having a high risk of toxicity (hormonal therapies excepted)’, at the beginning of the interview.
statistical analysis
original articles
Annals of Oncology
provided none of this information on the prescription and did not have the prescription verified.
patient information and education Specific notices regarding adverse events prevention and medication adherence, dedicated to patients, were available in most (82%) of the centres (Table 3). However, 54% of prescribers actually delivered it to their patients receiving oral chemotherapy for the first time. Twenty-eight percent of the centres had developed additional therapeutic educational material, and 12 clinicians (8%) practiced in centres where therapeutic education workshops were organised for patients. Additionally, one-third
Table 2. Prescribing practices for oral chemotherapy among the 157 prescribers Responders, n (%)a
Prescription type, n (%) Handwritten paper prescription 88 (56.1) Preprinted paper prescriptions 41 (26.1) Electronic order entry 61 (38.9) Compulsory requirements on prescription Diagnosis 19 (12.1) Protocol number (when 54 (34.4) appropriate) Cycle number 43 (27.4) Double check by another 13 (8.3) clinician Calculation of body surface area 42 (26.8) Calculation of dose/m2 84 (53.5) None 70 (44.6)
Frequency of use when used (%) 77 60 83
adherence and safety assessment Various methods for adherence and safety monitoring were reported as used by the responders: two-third (65%) declared having a dedicated logbook, half of the respondents declared their monitoring to be based on patients’ declaration (53%) and 23% declared having no formal monitoring (Table 4).The most objective monitoring method, pill counting, which is the most labour-intensive, was used by only 20 clinicians. Over the previous year, 39% of the clinicians said that they recalled at least one serious adverse event declaration, related to oral chemotherapy, in their centre. The majority of the responders (80%) said that they felt absolutely concerned about the risks of oral chemotherapy (Table 4). Univariate analysis included all variables described in Tables 1–3 and adherence assessment described in Table 4. Multivariate analyses included all variables with a P < 0.20 in the univariate analyses ( physician concerned by safety, other educational materials available and staff members in charge of patient education) and did not identify any practices associated to the recollection of serious adverse events.
differences across institutions
a
Sum of proportions can be higher than 100%, since several answers were possible for those questions.
Little differences as regard to prescribing practices were observed across institutions (supplementary Table S1, available at Annals of Oncology online). CCCs declared using additional educational material more often than their counterparts (51% versus 27% and 16% in public and private hospitals respectively, P = 0.03). Additional educational materials included videos, specific websites or educational workshops. The other responses to the questionnaire did not show differences in practices according to the type of centre.
Table 3. Educational programmes developed in the hospitals of the 157 prescribers Survey question (N = 157)
Responders, n (%)
Staff members in charge of patient education (multiple answers were possible) Senior oncologist 149 (95) Resident 28 (18) Nurse 55 (35) Pharmacist 10 (6) Other 35 (22) Written educational material provided to patients 129 (82) Educational material always given to patients at first 84 (54) prescription of oral chemotherapy Other educational materials available for patients 44 (28) Educational workshop available for patients 12 (8) Staff members responsible for education receive 57 (36) special training or certification internally
| Bourmaud et al.
Table 4. Monitoring of adherence and safety in the hospital of the 157 prescribers Survey question (N = 157)
Respondents, n (%)
Adherence assessment (multiple answers were possible) Logbook 102 (65) Patient’s declaration 83 (53) Pill count 20 (13) No formal process 36 (23) Safety Recollection of at least one ‘serious adverse drug 61 (39) event’ in the centre in the past year Recollection of at least one ‘serious near miss 32 (20) event’ in the centre in the past year Physician state they are definitely concerned by 126 (80) safety
Volume 25 | No. 2 | February 2014
Downloaded from http://annonc.oxfordjournals.org/ at University of Michigan on July 7, 2015
Survey question (N = 157)
of the clinicians were provided with training by their centre to teach them to provide therapeutic education to their patients (36%). Responders frequently shared responsibility with other health professionals [nurse (35%), residents (18%) and others (22%)] for educating patients (Table 3).
original articles
Annals of Oncology
discussion
Volume 25 | No. 2 | February 2014
conclusion In conclusion, the present study provides the first complete, inventory of the prescribing and monitoring practices for oral chemotherapy in a Western European country. It reveals a great heterogeneity in practices, with little implementation of
doi:10.1093/annonc/mdt553 |
Downloaded from http://annonc.oxfordjournals.org/ at University of Michigan on July 7, 2015
This study is one of the very few and to the best of our knowledge the only one carried out in Europe, evaluating prescription practices for oral chemotherapy in cancer patients. This study also gave us the opportunity to compare the results with those from the 2005 US [7]. The strengths of the present study include the high participation rate and the good representation of our sample; 20.1% of the prescribing oncologists, randomly selected, representing 23.7% of the French hospitals that prescribe oral chemotherapy replied to our questionnaire. In particular, all the French CCCs, 77% of the French teaching hospitals and 17% of the private hospitals replied. Like the results reported by Weingart et al., we report that, in 2012 in France, there is a great heterogeneity in the prescribing practices and monitoring for oral chemotherapy. The prescription requirements were noted on the oral chemotherapy prescription as rarely in the USA in 2005 as in France in 2012 (between 8.3% and 53.5%). Fewer than half of the clinicians follow the guidelines for the control and quality assurance procedures for their prescriptions. Fifty-six percent of the prescriptions are handwritten but more clinicians use electronic order entry systems (38.9% in France compared with 6% in the USA). Only 12 responders (8%) worked in hospitals where therapeutic education and monitoring programmes are available to patients. In 2005 in the USA as well as in 2012 in France, the proportion of hospitals offering special training or certification for those who educate patients about these medications is low; a third in the USA compared with 36% in France. The French prescribers in 2012 use the same methods for monitoring adherence as the American colleagues; labourintense, objective methods are rarely used ( pill count 13% in France compared with 21% in the USA), and, in both countries, one prescriber in four does not monitor treatment adherence formally. Although no adherence monitoring has yet proved to be reliable in assessing adherence, these methods might help in improving adherence among patients [3]. Eighty percent of respondents declared being concerned about these agents safety. This positive mind set could help in improving overall practices regarding prescription and monitoring of these agents. Thirtynine percent of the prescribers in our study reported that they recalled at least one treatment-related serious adverse event in their centre in the past year, which is almost twice than previoulsy reported in the American study (24%). This discrepancy could be due to differences regarding study period (2005 versus 2012), population of interest (USA versus France) or proportion of responders. Over the last 7 years, the increased number of patients receiving these agents could also have explained the high rate of adverse events recollection. Another, explanation could be that the prescribers pay more attention to the adverse events related to oral chemotherapy. This hypothesis is supported by the illustration of a high number of respondents declaring their concerns regarding safety (80%). The comparison between the various centres provided us with two pieces of information. The first is that the heterogeneity observed in oral chemotherapy prescribing practices is not correlated with the
type of hospital or oncologist (considering an a posteriori power estimated from 15% to 25%). The second is that the CCCs developed more new educational tools (51%) compared with 27% and 16% for the public and private general hospitals, respectively. The present study has limitations that need to be taken into account. First, the questionnaire survey design induced a selection bias. Hence, responders are likely to be more concerned about prescription of and patient adherence to oral chemotherapy. Also the response rates from the different types of hospital suggest the presence of a selection bias with 100% of the CCCs, compared with 17% of private hospitals and 23.6% of public hospitals. However, as results of the randomised selection and the large proportion of responders (60% of the sample), can be considered as an accurate snapshot of declared practices. Secondly, this study relies on a translated questionnaire which was completed by phone whereas the initial one was completed by mail. This may have led to unintended modification of meaning or misleading information. However, in way to limit these misinterpretations, the translated version of the questionnaire was modified according to French particularities and validated by five oncologists for its face validity and readability. In addition, the descriptive and closed questions of this questionnaire might also have helped in reducing influence of such variation to our general results. Thirdly, the declarative approach used for data collection, increased the risk that omission bias was present for the replies on what was included on the prescription and recollection of adverse events. Despite this bias, our results suggest that current prescription practices differ widely from recommendations and standardised good prescribing practices. Fourthly, in our study, oral chemotherapy was defined as ‘cytotoxic chemotherapies and targeted molecular therapies considered by the responding oncologist as having a high risk of toxicity (hormonal therapies excepted)’. This definition was necessarily limited and responders might not have shared a common appreciation of the concerned agents. However, this precision appeared essential to understand group of treatments concerned by this survey and might have helped in understand meaning of our results and comparability with the previous study [7]. Additionally, as regard to patient education, responders in our study often declared sharing this charge with nurses or junior physician. The exact role of these associated professionals remains unknown. Although a multidisciplinary approach is likely to improve quality of care, additional studies are needed to more carefully assess exact role of these professionals and their influence on oral chemotherapy management. Finally, despite similarities in cancer care across European countries [14], extent of our results to the remaining Europe remains to be evaluated. Nevertheless, our results provide evidences of a limited compliance to recommendations while prescribing oral chemotherapy and should encourage to a formal evaluation across Europe.
original articles the existing guidelines into clinical practice. It seems essential for health authorities to implement prescription standards, to more actively look for adverse events and to support development of therapeutic educational programmes, to prevent them to occur. These factors along with patients’ empowerment are forthcoming challenges in management of these chronically ill patients.
acknowledgements The authors thank Saul N. Weingart (Dana-Farber Cancer Institute) for sharing his questionnaire, for is attentive editing of this article and for his precious suggestions. They would also thank Margaret Haugh (MediCom Consult) for translation and editing services.
This work was supported by the Hygée Centre: manuscript translation fees.
disclosure YM has relationships with GlascoSmithKline that might have an interest in the submitted work. All remaining authors have declared no conflicts of interest.
references 1. Weingart SN, Brown E, Bach PB et al. NCCN Task Force Report: oral chemotherapy. J Natl Compr Canc Netw 2008; 6(Suppl 3): S1–14.
| Bourmaud et al.
2. Bedell CH. A changing paradigm for cancer treatment: the advent of new oral chemotherapy agents. Clin J Oncol Nurs 2003; 7(6 Suppl): 5–9. 3. Partridge AH, Avorn J, Wang PS et al. Adherence to therapy with oral antineoplastic agents. J Natl Cancer Inst 2002; 94(9): 652–661. 4. Birner A. Safe administration of oral chemotherapy. Clin J Oncol Nurs 2003; 7(2): 158–162. 5. Goodin S, Griffith N, Chen B et al. Safe handling of oral chemotherapeutic agents in clinical practice: recommendations from an international pharmacy panel. J Oncol Pract 2011; 7(1): 7–12. 6. Johnson PE, Chambers CR, Vaida AJ. Oncology medication safety: a 3D status report 2008. J Oncol Pharm Pract 2008; 14(4): 169–180. 7. Weingart SN, Flug J, Brouillard D et al. Oral chemotherapy safety practices at US cancer centres: questionnaire survey. BMJ 2007; 334(7590): 407. 8. Faithfull S, Deery P. Implementation of capecitabine (Xeloda) into a cancer centre: UK experience. Eur J Oncol Nurs 2004; 8(Suppl1): S54–S62. 9. Hartigan K. Patient education: the cornerstone of successful oral chemotherapy treatment. Clin J Oncol Nurs 2003; 7(6 Suppl): 21–24. 10. Jacobson JO, Polovich M, Gilmore TR et al. Revisions to the 2009 American Society of Clinical Oncology/Oncology Nursing Society chemotherapy administration safety standards: expanding the scope to include inpatient settings. J Oncol Pract 2012; 8(1): 2–6. 11. Weingart SN, Li JW, Zhu J et al. US Cancer Center Implementation of ASCO/ Oncology Nursing Society Chemotherapy Administration Safety Standards. J Oncol Pract 2012; 8(1): 7–12. 12. Neuss MN, Polovich M, McNiff K et al. 2013 Updated American Society of Clinical Oncology/Oncology Nursing Society chemotherapy administration safety standards including standards for the safe administration and management of oral chemotherapy. J Oncol Pract 2013; 9(2 Suppl): 5s–13s. 13. I national du cancer. Le traitement du cancer dans les établissements de santé en France en 2010: soins et vie des malades. Boulogne-Billancourt: Institut national du cancer 2010. 14. Ades F, Senterre C, de Azambuja E et al. Discrepancies in cancer incidence and mortality and its relationship to health expenditure in the 27 European Union member states. Ann Oncol 2013; 24(11): 2897–2902.
Volume 25 | No. 2 | February 2014
Downloaded from http://annonc.oxfordjournals.org/ at University of Michigan on July 7, 2015
funding
Annals of Oncology
Annals of Oncology Annals of Oncology 25: 500–504, 2014 doi:10.1093/annonc/mdt553 Published online 9 January 2014
Is oral chemotherapy prescription safe for patients? A cross-sectional survey A. Bourmaud1,2*,†, C. Pacaut3,†, A. Melis3, F. Tinquaut1, N. Magné4,5, Y. Merrouche2,3 & F. Chauvin1,2,6 1 Department of Public Health, Hygée Centre, Lucien Neuwirth Cancer Institut, Saint Priest en Jarez; 2Therapeutic Targeting in Oncology, EMR3738, Claude Bernard University, Lyon; Departments of 3Medical Oncology; 4Radiotherapy, Lucien Neuwirth Cancer Institut, Saint Priest en Jarez; 5Cellular and Biomolecular Radiobiology, EMR3738, Claude Bernard University, Lyon; 6Clinical Investigation Center and Clinical Epidemiology, CIE 3, Jean Monnet University, Saint-Etienne, France
Received 5 July 2013; revised 7 October 2013 and 30 October 2013; accepted 18 November 2013
introduction More than 25% of the 400 antineoplastic agents currently being developed are oral drugs, most of them being targeted molecular drugs [1]. This move towards developing oral drugs is driven by the potential advantages that oral treatment can provide for patients. Oral administration increases the patients’ autonomy by reducing the number of hospital visits, which is all the more important when the treatment is long term [2]. However, these new oral drugs bring a new set of problems including the need to assess and improve patient’s adherence [3] and to develop information on the management of treatment-related adverse events in outpatients [1].
*Correspondence to: Dr Aurélie Bourmaud, Department of Public Health, Hygée Centre, Lucien Neuwirth Cancer Institut, 108 bis avenue A. Raimond, 42 270 Saint Priest en Jarez, France. Tel: +33-477-917-477; Fax: +33-477-917-497; E-mail: [email protected] †
Both authors contributed equally.
Certain categories of oral chemotherapies, such as cytotoxic chemotherapies or targeted therapies, have similar toxicities to their i.v. counterparts [1, 4–6]. However, the levels of safety and monitoring for oral chemotherapy administration are less rigorous than those for i.v. chemotherapy administration [4, 7]. Despite recent guidelines and updates to guidelines, implementation of these recommendations in clinical practices seems heterogeneous, insufficient and is considered to be a priority in this field [1, 3–5, 7–12]. To date, only a single study carried out in 42 American comprehensive cancer centres (CCCs) was carried out to characterise current safety practices and identify variation in these practices in 2007 [7]. This study demonstrated wide variations in prescription practices, in the monitoring of toxicity and in the educational advice given to the patients. No recent data are available as regard to these practices and these information may help in developing and implementing adequate prescription guidelines. The main objective of this study was to achieve an exhaustive collection of information on prescription practices, monitoring
© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].
Downloaded from http://annonc.oxfordjournals.org/ at University of Michigan on July 7, 2015
Background: Oral chemotherapies are increasingly prescribed. Yet wide variations in prescription practices and in monitoring of toxicity have been underlined despite existing guidelines. There is little recent information available as regard to these practices. We aimed to obtain exhaustive information on oral chemotherapy prescription practices and safety monitoring in French hospitals. Methods: A cross-sectional multicentre survey was carried out to collect information on drug prescription, administration and surveillance: prescribing practices, coordination and monitoring of adherence, safety monitoring and side-effects occurrence prevention. Participants were a large sample of the French oncologists prescribing oral chemotherapy (20%). Results: One hundred and fifty-seven oncologists from 112 hospitals ( public, comprehensive cancer centres and private) replied (23.7% of cancer hospitals). The majority (56.1%) of the prescriptions were hand-written on a blank sheet. Eighty-four physicians (53.5%) included dose information and 36 (23%) declared having no monitoring procedures for adherence. Only 84 responders (54%) provided education material at first prescription of oral chemotherapy in way to limit avoidable side-effects. Sixty-one (39%) responders stated that they recalled at least one serious adverse event in the previous year declared in their centre. Conclusions: In this 2012 study, the majority of prescribers followed no standards in prescription writing, safety monitoring and toxicity prevention. The implementation of the international recommendations for oral chemotherapy administration should be considered as a top priority—for both prescribers and health authorities—as regards to the dynamic of development of these molecules and their potential side-effects. Key words: oral chemotherapy, prescription practices, safety monitoring, side-effects prevention, patient adherence, education of patient
original articles
Annals of Oncology
and management of patients taking oral chemotherapy prescribed by oncologists in France. The secondary objectives were to compare prescribing practices and level of recollection of adverse events across centres.
methods We carried out a cross-sectional, prospective and multicentre study of French oncologists between January 2012 and April 2012. We targeted all active oncologists prescribing oral chemotherapy in public and private hospitals or in a CCC.
questionnaire
The responders’ characteristics were analysed descriptively by the frequency ( percentages). The association between the type of centre and the frequency of recollection of severe adverse events and prescription practices was explored using univariate analyses. Binomial, stepwise multivariate logistic regression analyses were carried out for the dependant variable ‘reporting of a severe adverse event’. Variables with a P < 0.20 in the univariate analyses were included in the multivariate analyses with a significance threshold of P < 0.05. All analyses, except the spatial analyses, were carried out using SAS (version 9.1).
results responses Overall, 260 oncologists were proposed this survey, and 157 questionnaires were completed (20.1% of the 780 French oncologists). These questionnaires came from 112 different centres in France, including the French overseas departments and territories, i.e. 23.7% of the 473 French hospitals authorised to prescribe chemotherapy [13]. Our survey covered 56 public hospitals (i.e. 23.6% of the French public hospitals including 77% of French teaching hospitals), 20 CCC (i.e. all the French centres) and 36 private hospitals (i.e. 17% of the private hospitals specialised in cancer). Supplementary Figure S1, available at Annals of Oncology online shows that the distribution of the responders throughout France was uniform. The responders (Table 1) practiced mostly in the public sector (45.2%), and they were more often experienced doctors (89.2% hospital physicians compared with 10.2% residents).
study protocol Oncologists were contacted by phone from January 2012 to April 2012 to obtain their answers to the questionnaire by Pacaut during office hours. Information on serious adverse events recollection was based on respondents’ reports. Serious adverse events were defined as events associated to oral chemotherapy and either (i) a grade 4 toxicity requiring hospitalisation; (ii) resulting in work incapacity or (iii) considered as life-threatening and reported accordingly. If the investigator remembered a declaration of serious adverse events in his centre for at least one patient in the previous year, the event was coded as being a recollection of a serious adverse event.
data collected The responses to the questionnaire provided a description of oncologists’ current practices. We analysed the response rates in terms of geographic distribution. We also analysed the responses by type hospital ( public, private or CCC) and tried to identify specific prescription practices that could be associated with a recollection of serious adverse event.
prescribing Oral chemotherapy prescribing practices were highly variable, as were the compulsory elements required for each prescription (Table 2). Fifty-six percent of responders still use handwritten prescriptions, while 38.9% report using electronic order entry systems. The inclusion of the compulsory requirements for the prescription of the six most commonly used oral chemotherapies was also highly variable; 53.5% of the clinicians provided information on the dose; 26.8% provided the calculation of the body surface area; and only 8.3% had the prescription verified by another clinician. Almost half (44.6%) of the clinicians
Table 1. Characteristics of the 157 clinicians who replied to the questionnaire Characteristics (N = 157)
sample selection All practicing physicians are registered with the French Medical Board; there were 780 medical oncologists practicing in France at the start of this study. Our goal was to interview 20% (156 of 780) of those registered in order to obtain a representative sample, to allow feasibility of this study and to obtain a sufficient precision as regard to the answers. Sample size was calculated before study to allow a 5%–10% precision in the answer related to recollection of adverse event. Assumptions were based on the Weingart et al. study [7]. To reach this objective, we carried out a computer-generated randomisation (without stratification) to select 260 of them (one-third).
Volume 25 | No. 2 | February 2014
Type of centre Public sector Comprehensive cancer centre Private sector Function Professor Senior Resident No answer
Responders, n (%) 71 (45.2) 49 (31.2) 37 (23.6) 9 (5.7) 131 (83.5) 16 (10.2) 1 (0.6)
doi:10.1093/annonc/mdt553 |
Downloaded from http://annonc.oxfordjournals.org/ at University of Michigan on July 7, 2015
We used a French translation of the questionnaire on prescription practices used in 2005 in the study of American CCCs [7]. We obtained permission from Dr Weingart to translate and use the questionnaire for the same objective of collecting data on prescription practices in France. Two oncologists and a physician–methodologist translated the questionnaire; the translated questionnaire was tested on five local oncologists and modified to integrate their comments to improve its clarity while respecting the initial text. The English version of this questionnaire can be found online (supplementary Appendix, available at Annals of Oncology online). The questionnaire examined prescribing practices, safety monitoring, coordination and monitoring of adherence and education of patients about oral chemotherapy. Oral chemotherapy was defined to respondents as ‘cytotoxic chemotherapies and targeted molecular therapies considered by the responding oncologist as having a high risk of toxicity (hormonal therapies excepted)’, at the beginning of the interview.
statistical analysis
original articles
Annals of Oncology
provided none of this information on the prescription and did not have the prescription verified.
patient information and education Specific notices regarding adverse events prevention and medication adherence, dedicated to patients, were available in most (82%) of the centres (Table 3). However, 54% of prescribers actually delivered it to their patients receiving oral chemotherapy for the first time. Twenty-eight percent of the centres had developed additional therapeutic educational material, and 12 clinicians (8%) practiced in centres where therapeutic education workshops were organised for patients. Additionally, one-third
Table 2. Prescribing practices for oral chemotherapy among the 157 prescribers Responders, n (%)a
Prescription type, n (%) Handwritten paper prescription 88 (56.1) Preprinted paper prescriptions 41 (26.1) Electronic order entry 61 (38.9) Compulsory requirements on prescription Diagnosis 19 (12.1) Protocol number (when 54 (34.4) appropriate) Cycle number 43 (27.4) Double check by another 13 (8.3) clinician Calculation of body surface area 42 (26.8) Calculation of dose/m2 84 (53.5) None 70 (44.6)
Frequency of use when used (%) 77 60 83
adherence and safety assessment Various methods for adherence and safety monitoring were reported as used by the responders: two-third (65%) declared having a dedicated logbook, half of the respondents declared their monitoring to be based on patients’ declaration (53%) and 23% declared having no formal monitoring (Table 4).The most objective monitoring method, pill counting, which is the most labour-intensive, was used by only 20 clinicians. Over the previous year, 39% of the clinicians said that they recalled at least one serious adverse event declaration, related to oral chemotherapy, in their centre. The majority of the responders (80%) said that they felt absolutely concerned about the risks of oral chemotherapy (Table 4). Univariate analysis included all variables described in Tables 1–3 and adherence assessment described in Table 4. Multivariate analyses included all variables with a P < 0.20 in the univariate analyses ( physician concerned by safety, other educational materials available and staff members in charge of patient education) and did not identify any practices associated to the recollection of serious adverse events.
differences across institutions
a
Sum of proportions can be higher than 100%, since several answers were possible for those questions.
Little differences as regard to prescribing practices were observed across institutions (supplementary Table S1, available at Annals of Oncology online). CCCs declared using additional educational material more often than their counterparts (51% versus 27% and 16% in public and private hospitals respectively, P = 0.03). Additional educational materials included videos, specific websites or educational workshops. The other responses to the questionnaire did not show differences in practices according to the type of centre.
Table 3. Educational programmes developed in the hospitals of the 157 prescribers Survey question (N = 157)
Responders, n (%)
Staff members in charge of patient education (multiple answers were possible) Senior oncologist 149 (95) Resident 28 (18) Nurse 55 (35) Pharmacist 10 (6) Other 35 (22) Written educational material provided to patients 129 (82) Educational material always given to patients at first 84 (54) prescription of oral chemotherapy Other educational materials available for patients 44 (28) Educational workshop available for patients 12 (8) Staff members responsible for education receive 57 (36) special training or certification internally
| Bourmaud et al.
Table 4. Monitoring of adherence and safety in the hospital of the 157 prescribers Survey question (N = 157)
Respondents, n (%)
Adherence assessment (multiple answers were possible) Logbook 102 (65) Patient’s declaration 83 (53) Pill count 20 (13) No formal process 36 (23) Safety Recollection of at least one ‘serious adverse drug 61 (39) event’ in the centre in the past year Recollection of at least one ‘serious near miss 32 (20) event’ in the centre in the past year Physician state they are definitely concerned by 126 (80) safety
Volume 25 | No. 2 | February 2014
Downloaded from http://annonc.oxfordjournals.org/ at University of Michigan on July 7, 2015
Survey question (N = 157)
of the clinicians were provided with training by their centre to teach them to provide therapeutic education to their patients (36%). Responders frequently shared responsibility with other health professionals [nurse (35%), residents (18%) and others (22%)] for educating patients (Table 3).
original articles
Annals of Oncology
discussion
Volume 25 | No. 2 | February 2014
conclusion In conclusion, the present study provides the first complete, inventory of the prescribing and monitoring practices for oral chemotherapy in a Western European country. It reveals a great heterogeneity in practices, with little implementation of
doi:10.1093/annonc/mdt553 |
Downloaded from http://annonc.oxfordjournals.org/ at University of Michigan on July 7, 2015
This study is one of the very few and to the best of our knowledge the only one carried out in Europe, evaluating prescription practices for oral chemotherapy in cancer patients. This study also gave us the opportunity to compare the results with those from the 2005 US [7]. The strengths of the present study include the high participation rate and the good representation of our sample; 20.1% of the prescribing oncologists, randomly selected, representing 23.7% of the French hospitals that prescribe oral chemotherapy replied to our questionnaire. In particular, all the French CCCs, 77% of the French teaching hospitals and 17% of the private hospitals replied. Like the results reported by Weingart et al., we report that, in 2012 in France, there is a great heterogeneity in the prescribing practices and monitoring for oral chemotherapy. The prescription requirements were noted on the oral chemotherapy prescription as rarely in the USA in 2005 as in France in 2012 (between 8.3% and 53.5%). Fewer than half of the clinicians follow the guidelines for the control and quality assurance procedures for their prescriptions. Fifty-six percent of the prescriptions are handwritten but more clinicians use electronic order entry systems (38.9% in France compared with 6% in the USA). Only 12 responders (8%) worked in hospitals where therapeutic education and monitoring programmes are available to patients. In 2005 in the USA as well as in 2012 in France, the proportion of hospitals offering special training or certification for those who educate patients about these medications is low; a third in the USA compared with 36% in France. The French prescribers in 2012 use the same methods for monitoring adherence as the American colleagues; labourintense, objective methods are rarely used ( pill count 13% in France compared with 21% in the USA), and, in both countries, one prescriber in four does not monitor treatment adherence formally. Although no adherence monitoring has yet proved to be reliable in assessing adherence, these methods might help in improving adherence among patients [3]. Eighty percent of respondents declared being concerned about these agents safety. This positive mind set could help in improving overall practices regarding prescription and monitoring of these agents. Thirtynine percent of the prescribers in our study reported that they recalled at least one treatment-related serious adverse event in their centre in the past year, which is almost twice than previoulsy reported in the American study (24%). This discrepancy could be due to differences regarding study period (2005 versus 2012), population of interest (USA versus France) or proportion of responders. Over the last 7 years, the increased number of patients receiving these agents could also have explained the high rate of adverse events recollection. Another, explanation could be that the prescribers pay more attention to the adverse events related to oral chemotherapy. This hypothesis is supported by the illustration of a high number of respondents declaring their concerns regarding safety (80%). The comparison between the various centres provided us with two pieces of information. The first is that the heterogeneity observed in oral chemotherapy prescribing practices is not correlated with the
type of hospital or oncologist (considering an a posteriori power estimated from 15% to 25%). The second is that the CCCs developed more new educational tools (51%) compared with 27% and 16% for the public and private general hospitals, respectively. The present study has limitations that need to be taken into account. First, the questionnaire survey design induced a selection bias. Hence, responders are likely to be more concerned about prescription of and patient adherence to oral chemotherapy. Also the response rates from the different types of hospital suggest the presence of a selection bias with 100% of the CCCs, compared with 17% of private hospitals and 23.6% of public hospitals. However, as results of the randomised selection and the large proportion of responders (60% of the sample), can be considered as an accurate snapshot of declared practices. Secondly, this study relies on a translated questionnaire which was completed by phone whereas the initial one was completed by mail. This may have led to unintended modification of meaning or misleading information. However, in way to limit these misinterpretations, the translated version of the questionnaire was modified according to French particularities and validated by five oncologists for its face validity and readability. In addition, the descriptive and closed questions of this questionnaire might also have helped in reducing influence of such variation to our general results. Thirdly, the declarative approach used for data collection, increased the risk that omission bias was present for the replies on what was included on the prescription and recollection of adverse events. Despite this bias, our results suggest that current prescription practices differ widely from recommendations and standardised good prescribing practices. Fourthly, in our study, oral chemotherapy was defined as ‘cytotoxic chemotherapies and targeted molecular therapies considered by the responding oncologist as having a high risk of toxicity (hormonal therapies excepted)’. This definition was necessarily limited and responders might not have shared a common appreciation of the concerned agents. However, this precision appeared essential to understand group of treatments concerned by this survey and might have helped in understand meaning of our results and comparability with the previous study [7]. Additionally, as regard to patient education, responders in our study often declared sharing this charge with nurses or junior physician. The exact role of these associated professionals remains unknown. Although a multidisciplinary approach is likely to improve quality of care, additional studies are needed to more carefully assess exact role of these professionals and their influence on oral chemotherapy management. Finally, despite similarities in cancer care across European countries [14], extent of our results to the remaining Europe remains to be evaluated. Nevertheless, our results provide evidences of a limited compliance to recommendations while prescribing oral chemotherapy and should encourage to a formal evaluation across Europe.
original articles the existing guidelines into clinical practice. It seems essential for health authorities to implement prescription standards, to more actively look for adverse events and to support development of therapeutic educational programmes, to prevent them to occur. These factors along with patients’ empowerment are forthcoming challenges in management of these chronically ill patients.
acknowledgements The authors thank Saul N. Weingart (Dana-Farber Cancer Institute) for sharing his questionnaire, for is attentive editing of this article and for his precious suggestions. They would also thank Margaret Haugh (MediCom Consult) for translation and editing services.
This work was supported by the Hygée Centre: manuscript translation fees.
disclosure YM has relationships with GlascoSmithKline that might have an interest in the submitted work. All remaining authors have declared no conflicts of interest.
references 1. Weingart SN, Brown E, Bach PB et al. NCCN Task Force Report: oral chemotherapy. J Natl Compr Canc Netw 2008; 6(Suppl 3): S1–14.
| Bourmaud et al.
2. Bedell CH. A changing paradigm for cancer treatment: the advent of new oral chemotherapy agents. Clin J Oncol Nurs 2003; 7(6 Suppl): 5–9. 3. Partridge AH, Avorn J, Wang PS et al. Adherence to therapy with oral antineoplastic agents. J Natl Cancer Inst 2002; 94(9): 652–661. 4. Birner A. Safe administration of oral chemotherapy. Clin J Oncol Nurs 2003; 7(2): 158–162. 5. Goodin S, Griffith N, Chen B et al. Safe handling of oral chemotherapeutic agents in clinical practice: recommendations from an international pharmacy panel. J Oncol Pract 2011; 7(1): 7–12. 6. Johnson PE, Chambers CR, Vaida AJ. Oncology medication safety: a 3D status report 2008. J Oncol Pharm Pract 2008; 14(4): 169–180. 7. Weingart SN, Flug J, Brouillard D et al. Oral chemotherapy safety practices at US cancer centres: questionnaire survey. BMJ 2007; 334(7590): 407. 8. Faithfull S, Deery P. Implementation of capecitabine (Xeloda) into a cancer centre: UK experience. Eur J Oncol Nurs 2004; 8(Suppl1): S54–S62. 9. Hartigan K. Patient education: the cornerstone of successful oral chemotherapy treatment. Clin J Oncol Nurs 2003; 7(6 Suppl): 21–24. 10. Jacobson JO, Polovich M, Gilmore TR et al. Revisions to the 2009 American Society of Clinical Oncology/Oncology Nursing Society chemotherapy administration safety standards: expanding the scope to include inpatient settings. J Oncol Pract 2012; 8(1): 2–6. 11. Weingart SN, Li JW, Zhu J et al. US Cancer Center Implementation of ASCO/ Oncology Nursing Society Chemotherapy Administration Safety Standards. J Oncol Pract 2012; 8(1): 7–12. 12. Neuss MN, Polovich M, McNiff K et al. 2013 Updated American Society of Clinical Oncology/Oncology Nursing Society chemotherapy administration safety standards including standards for the safe administration and management of oral chemotherapy. J Oncol Pract 2013; 9(2 Suppl): 5s–13s. 13. I national du cancer. Le traitement du cancer dans les établissements de santé en France en 2010: soins et vie des malades. Boulogne-Billancourt: Institut national du cancer 2010. 14. Ades F, Senterre C, de Azambuja E et al. Discrepancies in cancer incidence and mortality and its relationship to health expenditure in the 27 European Union member states. Ann Oncol 2013; 24(11): 2897–2902.
Volume 25 | No. 2 | February 2014
Downloaded from http://annonc.oxfordjournals.org/ at University of Michigan on July 7, 2015
funding
Annals of Oncology
