can we prevent cytotoxic disasters?

Review

CAN WE PREVENT CYTOTOXIC DIASTERS?

The purpose of this review is to explore the realm of cytotoxicdisaster, which results in the accidental injury or death of apatient through an error or series of errors of chemotherapyadministration. It will also examine how a better under-standing of the processes that lead to these errors may helpto reduce future catastrophic accidental events. The discus-sion is divided into three main sections: a description of themagnitude of the problem; an outline of a series oftechniques to recognize and intercept such errors; and asummary of strategies for the prevention of cytotoxic errors.

The main focus of the review will be errors of commission,such as overdose, incorrect route of administration orincorrect formulation, as these best exemplify cytotoxicdisaster. However, errors of omission may be equally harmfulin allowing compromise of the aim of cure. Chemotherapyerror is not unique as a drug mishap, but the consequence ofsuch error has a greater potential for severe repercussionsthan with other classes of pharmaceuticals. Chemotherapyerrors share with other medication errors aetiologies thatinclude the fallibility of humans and the failure of systems tointercept the error before harm reaches the patient (Leapeet al, 1991) It is clear that most serious mishaps, whether ornot in the setting of chemotherapy administration, are aresult of a compounded series of errors rather than one event(Leape et al, 1995; Cohen et al, 1996).

Unfortunately, even as medicine and supportive technol-ogy advances, it is unlikely that we will ever completelyeradicate chemotherapy errors. There are a myriad of factorsthat contribute to this situation, including recognition of thecomplexity of cancer chemotherapy and the intricacy of thesystems that support its administration. There is a need for astructure that allows marked precision in the ordering,preparation and administration of chemotherapy. However,even a very good structure may be compromised by thedif®culty in maintaining and ensuring competence of highlyspecialized healthcare professionals who interact with eachof the elements of the chemotherapy system.

A contributing factor to continuing risk for error is anattitude of `it cannot happen here or to me' or that `itoccurred to him because of his incompetence'. From aphilosophical viewpoint, one must consider the wisdom ofperpetuating the impression of infallibility of physicians,nurses or pharmacists, or the system itself. Healthcareprofessional responsibility includes informing ourselves andour patients of these risks. An attitude of infallibility preventsthe remediation of error or processes leading to the error.

Open acknowledgement of vulnerability to error may lead toimprovement and institution of proper checks and balancesin the system.

MAGNITUDE AND SCOPE OF THE PROBLEM

An accurate picture of the magnitude in both frequency andseriousness of cytotoxic errors is dif®cult to ascertain. InCanada and in many other countries, there are no mandatednational, comprehensive reporting structures, nor is therean obligation on physicians or others to report errors.Indeed, for healthcare workers in most countries, a climate oflitigation, disciplinary action, potential demotion or lostadvancement opportunities and the stigma of being asso-ciated with an error tend to discourage reporting of errors(Brennan et al, 1991; Leape et al, 1995; Hingorani et al,1999). A related issue is the general paucity of systematiccollection of `near misses', in which errors are detectedbefore the patient is harmed. All the disincentives toreporting described above are operative in the situation ofa near miss, in spite of no harm being accrued to the patient.Thus, there exists an even smaller likelihood of reporting andopportunity for prevention of further incidents.

From a patient perspective, Hingorani et al. (1999)reported that physicians are less likely to disclose theoccurrence of an adverse event than patients report thatthey would like. It has been postulated that, in addition to thewish to avoid anxiety in patients, physicians avoid reportingadverse events to patients because error is often automati-cally equated with incompetence, because the task isunpleasant and time consuming and because there is afear of losing trust, being blamed or being sued (Leape et al,1995; Hingorani et al, 1999). Many chemotherapy errorscannot be hidden even if one wanted to and should not be forat least three reasons. First, there may be speci®c interven-tions required that may positively affect the eventualoutcome (Spiegel et al, 1984; Pierga et al, 1992). Secondly,discovery by the patient of an undisclosed error would lead tofurther erosion of trust and con®dence, thereby compound-ing the original harm. Thirdly, adopting a paternalisticattitude of not allowing anxiety fails to acknowledge thatpatients increasingly wish to have control of their healthcareand the decisions around it and therefore have a right to thisknowledge.

A number of studies (not restricted to chemotherapy) haveexamined the incidence of drug errors and iatrogenicmorbidity and mortality in hospitalized patients (Brennanet al, 1991; West et al, 1994; Leape et al, 1991, 1995; Bateset al, 1995; Dean et al, 1995; Phillips et al, 1998). Thesestudies have shown that adverse drug events occur in

British Journal of Haematology, 2000, 108, 464±469

464 q 2000 Blackwell Science Ltd

Correspondence: Conrad V. Fernandez, I.W.K. Grace Health Centre

for Children, Women and Families, 5850/5980 University Avenue,

PO Box 3070, Halifax, Nova Scotia, B3J 3G9, Canada.

3´7±6´5% of hospitalized patients. In one study of adverseevents resulting from drugs, operations and diagnosticprocedures, 30% of the events resulted in disability lastingmore than 6 months, 2´6% resulted in permanent injury and13´6% resulted in death (Brennan et al, 1991). Theproportion of these adverse events attributable to errors ofdrug administration was as high as 48% (Brennan et al,1991; Leape et al, 1995). Overall, errors by physicians andother healthcare workers contribute in a signi®cant way topatient disability or death, as well as resulting in costlyinterventions (Schneider et al, 1995). The frequency of nearmisses or potential errors has also been documented in theliterature, although the true number is harder to assess andis probably underestimated. Oncology patients are certainlynot immune to these general risks (Brennan et al, 1991).

There have been numerous case reports and severalsummaries of chemotherapy errors leading to death ordisability (Mortensen et al, 1992; Trinkle & Wu, 1996;Fernandez et al, 1998; Mehta et al, 1998). A wide variety ofcircumstances and contributing factors lead to these errorsand include overdose, incorrect route of administration andsubstitution of one drug for another. Some errors, such asintrathecal vincristine installation, continue to occur despitethree decades of case reports describing its dangers(Schochet et al, 1968; Shepherd et al, 1978; Bain et al,1991; Fernandez et al, 1998). These reports underscore theneed for continued education of healthcare workers involvedin chemotherapy administration, vigilance and assessmentof systems and the unfortunate likelihood that error willcontinue to occur.

Trinkle & Wu (1996) conducted a MEDLINE reviewencompassing the period from 1966 to 1993 for paediatricchemotherapy errors and found 52 cases involving primarilyoverdoses or inadvertent intrathecal injection of chemo-therapy. Fourteen of these cases resulted in a fatal outcome(seven of intrathecal vincristine, four of intravenous vincris-tine overdose, two of intrathecal methotrexate overdose andone of intrathecal daunorubicin). The most common non-fatal error was that of intravenous vincristine overdose. Thereport did not review putative causes for the errors. A recentcase report and review of the literature documents thecauses of inadvertent intrathecal vincristine administration(Fernandez et al, 1998). The reasons for error found in thisreport included mistaking intravenous vincristine for one ofthe intrathecal therapies to be given, not recognizing thatvincristine was not to be given intrathecally and failing tocheck physician orders. Pharmacy or nursing error wasuncommonly identi®ed as a major contributing factor to theultimate compromise of the patient but, clearly, as part of thesystem, could have played a role in recognition andprevention of the error.

A review (1991±98) of the National Chemotherapy ErrorsDatabase run by the United States Pharmacopeia MedicationErrors Reporting Program cited 38 reports of chemotherapyerrors or near misses occurring in 40 patients (Mehta et al,1998). Twenty-eight patients in this review were reported tohave received an incorrect drug, an incorrect dose orincorrect route of administration. Six of these patients died,and 13 suffered signi®cant disability. The majority of the

errors were found to involve confusing similar looking orsounding drugs. In these cases, either the wrong drug wasordered, or the dose for another similar drug was substituted(i.e. carboplatin dosing used for cisplatin dosing, resulting insevere toxicity, including hearing loss, renal failure or death).Seven cases were reported to have the intended amount overthe entire course of treatment given as a single daily dose (i.e.cyclophosphamide intended as 1 g/m2/day ´ 4 days given as4 g/m2/day ´ 4 days). Overdoses of this nature led to thegreatest mortality and morbidity in this study.

The estimated rate of error (0´06%) in the administrationof very high dose chemotherapy, such as seen in bonemarrow transplant settings, is similar to that seen in generalmedicine. In one bone marrow transplantation study, themost common error was that of inadvertent overdose eitherby administering the intended cumulative dose as a singledose or by nursing infusion errors (Chen et al, 1997). Theerrors occurred more frequently in less established trans-plant units, suggesting that familiarity with the protocolsand techniques of this procedure was important to the eventoccurring. A separate US study demonstrated that juniorhouse staff were more likely to err in medication orders thanconsultant staff. However, one should note that theconsultant staff had a small, but signi®cant, de®ned rate oferror, which con®rmed the statement that no individual isimmune to error (Folli et al, 1987).

System designers must consider that all individuals, nomatter how skilled or experienced, are at risk of makingserious errors. They must recognize and support criticalcheck-points, accommodate multiple skill levels andincorporate processes for validating internal safety.

IDENTIFICATION OF ERRORS/SYSTEMS ANALYSIS

The need for error-free systems in such sensitive domains asaviation, nuclear power plants and other mission-criticalareas has provided models for similar applications tomedicine. Taxonomies of active error types have beendeveloped upon which to structure these models (Rasmus-sen, 1982; Reason, 1990; Runciman et al, 1993; Arnstein,1997). These include contextual classi®cations (in whichactions that lead to an error are described in relation toenvironment), modal classi®cations (in which errors arecategorized, such as omission, repetition or substitution) andpsychological classi®cations (Table I). The ®rst two classi®ca-tions of error are not very conducive to determining thecause of an error. However, the psychological classi®cation ofcognitive processing describes why an error occurred, andcan therefore be used to predict how it may be prevented(Rasmussen, 1982; Reason, 1990).

It has become increasingly understood that psychologicalerrors are to be interpreted recognizing that they exist indynamic, complex systems, which include human±technicalinterfaces, multiple points of entry and potential feed-back,psycho-social variables of individuals and group safetyculture (i.e. poor attitudes leading to error) (Rasmussen,1990; Runciman et al, 1993; Kirwan, 1998a). Latent errors(contributing factors) have a powerful in¯uence in shapingpsychological errors. Examples of these include fatigue, poor

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design of equipment, lack of adequate training of personnel,multiperson interactions and lack of appropriate work space(Runciman et al, 1993).

Latent errors may allow an error to occur in a system thatappears safe when optimum conditions are present, but istruly unsafe because of the potential latent weaknesses.

There are multiple human error identi®cation techniquesfor risk assessment in high-risk systems. Kirwan (1998a,b)reviewed these techniques extensively and classi®es them astaxonomies of error, psychologically based tools, cognitivemodelling tools, cognitive simulations and reliability-orien-tated tools. Their application in medicine has fallen into anumber of broad strategies, including systems error analysis,medication error de®nitions and classi®cations, speci®cpharmacist interventions, severity-indexed, incident report-based medication error programmes and educational inter-ventions (Betz & Levy, 1985; Blum et al, 1988; Hartwig et al,1991; Schneider & Hartwig, 1994; Cohen et al, 1996). Thesystem errors identi®cation methods are complementary toeach other, and many of these strategies have beenincorporated into the management of quality and safety insuccessful chemotherapy programmes.

One of the more robust methods of error reduction issystems analysis, in which each step of a process is carefullyexamined (for example, in the case of chemotherapyadministration, from manufacture and packaging to phar-macy handling of the drug to healthcare workers' main-tenance of competence to speci®c interventions at thebedside). In this model, attention is initially focused onapplications and time-points that, in the event of error,would result in the death of or injury to the patient.Interventions are then devised at points at which errors aremost likely to occur or where an error would have acatastrophic outcome. The ascertainment of these points isfacilitated by a current database of actual and potentialerrors. The information from the database can be used todetermine whether theoretical risks are indeed real, toidentify areas that are not intuitively obvious and as asubsequent quality assurance process. There should be amechanism in all centres that administer chemotherapy tocapture and review errors, and to recommend systemchanges.

Schneider & Hartwig (1994) described a severity-indexed,incident report-based medication error reporting

programme that determined error rates, the distribution oferrors by severity and the error types. Their results allow forfocus on the system breakdown points and drug classes mosthighly associated with error. The system breakdown points,in rank order of most frequent to least frequent, were errorsin administration, errors in transcription, errors in drugavailability, errors in communication, errors in medicationordering and errors in dispensing. Charting and labellingproblems were infrequent. Clearly, some of these systembreakdown points may occur in oncology settings and canand should be used as a guide to examine the functioningand safety of local chemotherapy programmes.

A third strategy is to use the skills of pharmacists (Betz &Levy, 1985; Folli et al, 1987; Hartwig et al, 1992;Hutcherson & Gammon, 1997). Severity-indexed (errorsgraded by potential or actual harms), voluntary or observa-tional medication error programmes overseen by thepharmacy service can be used to identify trends in types oferrors (omissions, incorrect dose, time, rate, frequency orroute of drug) and in systems breakdown points (physicianorder, transcription, charting, dispensing/labelling or admin-istration). These trends can then be used to interveneappropriately.

A number of studies have demonstrated a reduction indrug error rates through pharmacist interventions. Onestudy using clinical pharmacists demonstrated a medicationorder error rate of <4´9 per 1000 medication orders (Folliet al, 1987). All physician orders were screened againstformularies, protocols and experience. Five per cent of theerrors intercepted by pharmacists were potentially lethal. Ingeneral, the reported medication ordering error rate rangedfrom 0´3% to 1´9% (Blum et al, 1988) Thus, where clinicalprogrammes are large and busy, a dedicated oncologypharmacist is invaluable and should be mandated. Smallprogrammes, in which the volume to maintain physician,nurse and pharmacist expertise is low, should also have atrained pharmacist as a resource, as well as strict rules aboutwho can and cannot order, process, dispense and administerchemotherapy.

PREVENTION OF CYTOTOXIC ERRORS

The prevention of errors in complex systems requires anorganized approach, which can address the multiple

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Table I. Classi®cation of cognitive processing errors.

Error type De®nition Examples

Skill-based errors Dissociation between automatic modes of action Omission of checking whichand conscious control chemotherapy agent is being injected

Rule-based errors Failure to apply a rule designed to avoid error or Failure to check that a vein is free ¯owing

application of an inappropriate rule or a poor rule before injecting a vesicant chemotherapy agent

Cognitive-based errors Error that results from inadequate Inadequate knowledge that the chemotherapy

knowledge/experience or problem-solving de®ciencies is an overdose or wrong for that cancer

Summarized from Rasmussen (1982) and Reason (1990).

contributing factors that may lead to the end-result of harmto the patient. A stepwise approach is summarized in Table II(Runciman et al, 1993; Reason, 1990). General designprinciples for reducing error include integrating designerand user knowledge to develop an accurate model of thesystem, simplifying the structure of tasks, making theexecution and evaluation of a task discernible, exploitingnatural actions and natural or arti®cial constraints, design-ing with the expectation that error will occur andconsidering standardization (Reason, 1990). Many or all ofthese strategies may be incorporated into a chemotherapysafety programme.

Several sources have suggested standards for the deliveryof cancer chemotherapy in a safe manner, recognizing that itis potentially delivered in a number of hospital and othersettings (Cohen et al, 1996; Fischer et al, 1996; Woodmanet al, 1996). The Joint Council for Clinical Oncology in theUK has recommended the following regarding cancerchemotherapy (as summarized by Woodman et al, 1996):

1 That it be carried out in designated, properly equippedareas;

2 That it should be carried out by experienced, trained staff;3 That regimens be initiated by appropriately trained

oncology staff;4 That the speci®c protocol be available on the ward, in the

clinic and in the pharmacy;5 That speci®c checks be made before administration of the

chemotherapy, including con®rmation of the regimen,identi®cation of the patient, con®rmation of the drug,dose, route of administration, frequency and diluent;

6 That cancer therapy be undertaken during normalworking hours if possible; and

7 That the consultant involved is responsible for the safeinstitution of procedures and practices.

Additional recommendations focusing on addressing skill-,rule- and knowledge-based cognitive errors include not

accepting verbal chemotherapy orders, the need for inde-pendent recalculation of drug dosing, the necessity of doublechecking chemotherapy orders and administration by asecond quali®ed person, the avoidance of drug acronyms,abbreviations and brand names and the use of standardpreprinted chemotherapy orders and checklists. (Cohen et al,1996; Fischer et al, 1996; Fernandez et al, 1998). Some ofthe responsibility also lies at the manufacturer level inconsidering and predicting name confusion or manufactur-ing drugs in volumes or colours that may enhance patternrecognition (Cohen et al, 1996). In addition, assistance withthe education of healthcare workers before and at the time ofintroduction of new products has been suggested by some tobe a manufacturer responsibility. Finally, empoweringpatients as their own advocates, through education aboutthe chemotherapy that they are to receive, is an added safetycheckpoint.

Despite these recommendations, there are a number ofhospitals and pharmacies working under suboptimal condi-tions (Fischer et al, 1996; Woodman et al, 1996) Althoughoncology nurses are usually speci®cally trained and certi®edin chemotherapy administration, physicians may not bequali®ed to administer these agents. It is perhaps one of themost vital aspects of preventing chemotherapy errors thatmaintenance of competence be made a high priority in anycentre that plans to administer chemotherapy. One may havean elaborate checklist and safety net of recommendationsbut, if individuals at all levels of the chemotherapy processare not aware of the dangerous nature of these agents,further disasters are sure to occur.

One must be cautious that policies that are implementedare workable. Policies that are overly complex, allow forinterpretation, are cumbersome to use, not clearly written ornot developed in conjunction with the ultimate users aredestined to add more opportunity for error, rather than toameliorate it. Untenable policies lead to a `normalization ofdeviance' in which standards are collectively reduced and

467Review


Table II. An approach to the identi®cation and prevention of errors.

Steps to error prevention Examples of mechanisms

1. Determine what errors are occurring Morbidity/mortality/incident reports,(non-punitive forum) simulation/observation studies

2. Collect information and prioritize based on severity index Pharmacy and therapeutics/morbidity/

(potential or actual errors) formal chemotherapy review committees

3. Categorize errors ± skill-based, rule-based, knowledge-based, technical Use human error identi®cation techniques

4. Categorize latent or contributing factors Design reports to capture negative or positivein¯uences on error outcome/occurrence

5. Develop strategies/policies/procedures ± Multidisciplinary input, risk/bene®t

prevention, detection, minimizing error analysis, national standards

6. Implement strategies/policies/procedures Education of and feedback from user groups,

need to be functional and understandable

7. Determine whether strategy is effective Return to no. 1

Summarized from Reason (1990); Runciman et al. (1993); Arnstein (1997); Kirwan (1998a).

accepted, usually because the group has been fortunateenough not to have a critical incident occur (Vaughan,1996). Multidisciplinary checkpoints at physician, phar-macy, nursing and institutional levels should be clear, andthe role of each individual supported. If the responsibility forensuring the safe administration of the chemotherapy isdelegated, either to untrained staff or to the next individual,errors are more likely to occur.

The continued reporting and analysis of previous errors isessential, both internally and in the medical literature, toeducate and guide other facilities. This means not onlyreporting errors that occur de novo, but establishing amechanism whereby policies developed to address previouserrors are evaluated in practice.

A number of factors may in¯uence whether or not anerror is reported, including fear of disciplinary action,disagreement over whether or not an error occurred andthe effort required to make the report. One of the strategiesdescribed to overcome this reluctance to report adverseevents secondary to errors is a switch in emphasis fromdisciplinary action to collaborative involvement in improvingthe systems that allowed the error to occur. Individualculpability should be reserved for signi®cant departures fromacceptable practice when there are no mitigating factors(Runciman et al, 1993). A pilot project at the Children'sHospital of Philadelphia has shown a marked reduction inerrors by exactly such an approach (B. Bickert, personalcommunication). An important component of this tactic isrecognition by all multidisciplinary parties involved (physi-cians, nurses and pharmacists) that the organization ofchemotherapy administration brings presumptions andobstacles that may be unique to their own speci®c role.Multidisciplinary collaboration to identify and solve systemserrors is therefore the key.

CONCLUSIONS

In answer to the question: Can we prevent cytotoxicdisasters?, the conclusion is that it is unlikely that we willbe able to eliminate these errors completely. Reliance onindividual vigilance, the threat of discipline and the diligenceof others will always be insuf®cient, especially in complexsystems such as human medicine.

This review shows clearly that we can, however,signi®cantly reduce the additional burden to our patientsof adverse effects from error through a curtailing of thefrequency and possibly the consequences of chemotherapymishaps. Dedicated oncology pharmacists, institutional rulesof chemotherapy preparation and administration, systematicand repeated analysis of programmes, maintenance ofcompetence of healthcare workers, careful documentationand reporting of errors and evaluation of new policies are allessential elements in attempting to reduce morbidity andmortality from chemotherapy error. Institutions should beencouraged to maintain formal chemotherapy reviewprocedures, possibly as a subcommittee of the localpharmacy and therapeutics committee.

A non-punitive approach to the identi®cation of error andpotential error should be fostered to encourage reporting at

all levels and by all participants in the chemotherapyprocess. A practice built on censure in response to drugerror is only likely to drive these errors and the potential forprevention out of sight. This will then subvert a key tenet ofsystems analysis, which is the free sharing of multidisciplin-ary experience in recognizing potential points of concern inthe chemotherapy administration process.

Consideration should be given to the establishment notonly of central registries of errors, such as the NationalChemotherapy Errors Database in the United States, but alsoof information sites (such as Internet web sites) in whichexperience about the prevention and treatment of cytotoxicerrors could be available. Co-operative Oncology Groupswould have access to resources so that they could be idealmanagers of such a site (Lampkin & Wells, 1996; Fernandezet al, 1998).

All these steps should establish a co-operative system tominimize cytotoxic errors. Although the prospect of perfec-tion is unlikely, we have an obligation to our patients and ourcoworkers to maximize the reduction of error by carefulsystems analysis and adherence to well thought out rules ofconduct.

ACKNOWLEDGMENTS

The author would like to thank Dr Dorothy Barnard and MsBarb McCully for critical review of the manuscript.

IWK Grace Health Centre C O N R A D V.for Children, Women and Families, F E R N A N D E Z

5850/5980 University Avenue,PO Box 3070, Halifax,Nova Scotia, B3J 3G9, Canada

REFERENCES

Arnstein, F. (1997) Catalogue of human error. British Journal of

Anaesthesia, 79, 645±656.Bain, P.G., Lantos, P.L., Djurovic, V. & West, I. (1991) Intrathecal

vincristine: a fatal chemotherapeutic error with devastating

central nervous system effects. Journal of Neurology, 238, 230±

234.Bates, D.W., Cullen, D.J., Laird, N., Petersen, L.A., Small, S.D., Servi,

D., Laffel, G., Sweitzer, B.J., Shea, B.F., Hallisey, R., Vliet, M.V.,

Nemeskal, R. & Leape, L.L. (1995) Incidence of adverse drug

events and potential adverse drug events. Implications forprevention. Journal of the American Medical Association, 274, 29±

34.

Betz, R.P. & Levy, H.B. (1985) An interdisciplinary method ofclassifying and monitoring medication errors. American Journal of

Hospital Pharmacy, 42, 1724±1832.

Blum, K.V., Abel, S.R., Urbanski, C.J. & Pierce, J.M. (1988)

Medication error prevention by pharmacists. American Journal ofHospital Pharmacy, 45, 1902±1903.

Brennan, T.A., Leape, L.L., Laird, N.M., Hebert, L., Localio, A.R.,

Lawthers, A.G., Newhouse, J.P., Weiler, P.C. & Hiatt, H.H. (1991)

Incidence of adverse events and negligence in hospitalizedpatients. Results of the Harvard Medical Practice Study I. New

England Journal of Medicine, 324, 370±376.

Chen, C.S., Seidel, K., Armitage, J.O., Fay, J.W., Appelbaum, F.R.,Horowitz, M.M., Shpall, E.J., Weiden, P.L., Antman, K.S.,

Champlin, R.E., Kersey, J.H. & Sullivan, K.M. (1997) Safeguarding

468 Review


the administration of high-dose chemotherapy: a national

practice survey by the American Society for Blood and Marrow

Transplantation. Biology of Blood and Marrow Transplantation, 3,

331±340.Cohen, M.R., Anderson, R.W., Attilio, R.M., Green, L., Muller, R.J. &

Pruemer, J.M. (1996) Preventing medication errors in cancer

chemotherapy. American Journal of Health-System Pharmacists, 53,

737±746.Dean, B.S., Allan, E.L., Barber, N.D. & Barker, K.N. (1995)

Comparison of medication errors in an American and a British

hospital. American Journal of Health-System Pharmacists, 52,2543±2549.

Fernandez, C.V., Esau, R., Hamilton, D., Fitzsimmons, B. & Pritchard,

S. (1998) Intrathecal vincristine: an analysis of reasons for

recurrent fatal chemotherapeutic error with recommendations forprevention. Journal of Pediatric Hematology/Oncology, 20, 587±

590.

Fischer, D.S., Alfano, S., Knobf, M.T., Donovan, C. & Beaulieu, N.

(1996) Improving the cancer chemotherapy use process. Journalof Clinical Oncology, 14, 3148±3155.

Folli, H.L., Poole, R.L., Benitz, W.E. & Russo, J.C. (1987) Medication

error prevention by clinical pharmacists in two Children'sHospitals. Pediatrics, 79, 718±722.

Hartwig, S.C., Denger, S.D. & Schneider, P.J. (1991) Severity-indexed,

incident report-based medication error-reporting program. Amer-

ican Journal of Hospital Pharmacy, 48, 2611±2616.Hartwig, S.C., Siegel, J. & Schneider, P.J. (1992) Preventability and

severity assessment in reporting adverse drug reactions. American

Journal of Hospital Pharmacy, 49, 2229±2232.

Hingorani, M., Wong, T. & Va®dis, G. (1999) Patients' and doctors'attitudes to amount of information given after unintended injury

during treatment: cross sectional, questionnaire survey. British

Medical Journal, 318, 640±641.

Hutcherson, D.A. & Gammon, D.C. (1997) Preventing errors withantineoplastic agents. Hospital Pharmacy, 32, 194±202.

Kirwan, B. (1998a) Human error identi®cation techniques for risk

assessment of high risk systems. Part 1: review and evaluation oftechniques. Applied Ergonomics, 29, 157±177.

Kirwan, B. (1998b) Human error identi®cation techniques for risk

assessment of high risk systems. Part 2: towards a framework

approach. Applied Ergonomics, 29, 299±318.Lampkin, B.C. & Wells, R. (1996) Intrathecal leukovorin after

intrathecal methotrexate (editorial). Journal of Pediatric Hematology/

Oncology, 18, 249.

Leape, L.L., Brennan, T.A., Laird, N., Lawthers, A.G., Localio, A.R.,Barnes, B.A., Hebert, L., Newhouse, J.P., Weiler, P.C. & Hiatt, H.

(1991) The nature of adverse events in hospitalized patients.

Results of the Harvard Practice Study II. New England Journal ofMedicine, 324, 377±384.

Leape, L.L., Bates, D.W., Cullen, D.J., Cooper, J., Demonaco, H.J.,

Gallivan, T., Hallisey, R., Ives, J., Laird, N., Laffel, G., Nemaskal, R.,

Petersen, L.A., Porter, K., Servi, D., Shea, B.F., Small, S.D.,Sweitzer, B.J., Thompson, B.T. & Vliet, M.V. (1995) Systems

analysis of adverse drug events. Journal of the American Medical

Association, 274, 35±43.

Mehta, P., Beltz, S. & Cousins, D. (1998) A review of the national

chemotherapy errors database and recommendations for safe

administration. International Journal of Pediatric Hematology/

Oncology, 5, 463±473.

Mortensen, M.E., Cecalupo, A.J., Lo, W.D., Egorin, M.J. & Batley, R.(1992) Inadvertent intrathecal injection of daunorubicin with

fatal outcome. Medical and Pediatric Oncology, 20, 249±253.

Phillips, D.P., Christenfeld, N. & Glynn, L.M. (1998) Increase in US

medication-error deaths between 1983 and 1993. The Lancet,351, 643.

Pierga, J., Beuzeboc, P., Dorval, T., Palangie, T. & Pouillart, P. (1992)

Favourable outcome after plasmapharesis for vincristine overdose.The Lancet, 340, 185.

Rasmussen, J. (1982) Human errors: a taxonomy for describing

human malfunction in industrial incidents and accidents. Journal

of Occupational Accidents, 4, 311±333.Rasmussen, J. (1990) The role of error in organizing behaviour.

Ergonomics, 33, 1185±1189.

Reason, J.T. (1990) Human Error. Cambridge University Press,

Cambridge, UK.Runciman, W.B., Sellen, A., Webb, R.K., Williamson, J.A., Currie, M.,

Morgan, C. & Russell, W.J. (1993) Errors, incidents and accidents

in anaesthetic practice. Anaesthesia and Intensive Care, 21, 506±519.

Schneider, P.J. & Hartwig, S.C. (1994) Use of severity-indexed

medication error reports to improve quality. Hospital Pharmacy,

29, 208±211.Schneider, P.J., Gift, M.G., Lee, Y.P., Rothermich, E.A. & Sill, B.E.

(1995) Cost of medication-related problems at a university

hospital. American Journal of Health-System Pharmacists, 52,

2415±2418.Shepherd, D.A., Steuber, C.P., Starling, K.A. & Fernbach, D.J. (1978)

Accidental intrathecal administration of vincristine. Medical and

Pediatric Oncology, 5, 85±88.

Schochet, S.S. Jr, Lampert, P.W. & Earle, K.M. (1968) Neuronalchanges induced by intrathecal vincristine sulfate. Journal of

Neuropathology and Experimental Neurology, 27, 645±658.

Spiegel, R.J., Cooper, P.R., Blum, R.H., Speyer, J.L., McBride, D. &Mangiardi, J. (1984) Treatment of massive intrathecal metho-

trexate overdose by ventriculolumbar perfusion. New England

Journal of Medicine, 311, 386±388.

Trinkle, R. & Wu, J.K. (1996) Errors involving pediatric patientsreceiving chemotherapy: a literature review. Medical and Pediatric

Oncology, 26, 344±351.

Vaughan, D. (1996) The Challenger Launch Decision. Risky Technology,

Culture and Deviance at NASA. University of Chicago Press, Chicago.West, D.W., Levine, S., Magram, G., MacCorkle, A.H., Thomas, P. &

Upp, K. (1994) Pediatric medication order error rates related to

the mode of order transmission. Archives of Pediatric and AdolescentMedicine, 148, 1322±1326.

Woodman, C., Nicolson, M., Hare, L., So, J., Hey, R., McIllmurray, M.

& Crowther, D. (1996) Towards quality control in cancer

chemotherapy. British Journal of Cancer, 73, 117±118.

Keywords: adverse drug events, human error, chemotherapy,systems analysis.

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