Patient Safety Tip of the Week
May 5, 2015 Errors with Oral Oncology
Drugs
Most reports on
chemotherapy errors have focused on IV or intrathecal chemotherapy agents. But
oral chemotherapy agents have been increasing in number and reports of errors
relating to them are beginning to appear. Several recent articles provide
important lessons to avoid such incidents.
ISMP Canada last
month published an analysis of incidents involving oral chemotherapy agents
that were reported to their incident database or to a national Canadian
incident reporting database (ISMP
Canada 2015). They analyzed 516 incidents over a 12 year period and while
patient harm or death occurred in only a small minority of cases there were
multiple lessons learned. They were able to identify 3 major themes: (1)
lack of specialized knowledge by care providers (2) medication name mix-ups and
(3) lack of safe medication handling processes. They provide case examples to
illustrate each of these themes.
Chemotherapy
regimens can be very complex and ISMP Canada notes that community pharmacists
may not have a good understanding of chemotherapy cycles, side-effect profiles,
etc. The same applies to many other non-oncologist healthcare professionals. As
a result, patient education on these complex issues may be insufficient. The
example they provide is a patient who was on a protocol-defined capecitabine
cyclical dosing regimen who was mistakenly given capecitabine daily when
admitted as an inpatient and then the prescription given the patient at
discharge also erroneously called for daily capecitabine. You may recognize
this problem of prescribing a drug daily rather than on a different regimen because
we’ve written about very similar problems with methotrexate in the past (see
our What’s New in the Patient Safety World columns for July 2010 “Methotrexate
Overdose Due to Prescribing Error” and July 2011 “More
Problems with Methotrexate”).
As a subtheme of the
“lack of specialized knowledge” they mention that failure to include some
critical information on the prescriptions may contribute. Such information might
include diagnosis, patient height and weight, duration of the chemotherapy
cycle, etc.
The second theme,
medication name mix-ups, of course is not unique to chemotherapy agents. The
ISMP Canada study notes a partial list of some of these easily mistaken drug
name pairs, which may include confusion between brand names, between generic
names or between brand and generic names. (Note that ISMP Canada is putting
together a list of easily confused medications with TALLman lettering
recommendations and ISMP
in the US has recently updated its list of confused medication names.) It
discusses the importance of using TALLman lettering to help avoid such errors,
as well as including the indication and both brand and generic drug names on
prescriptions and use of barcoding. Note that another recent article (O’Rourke
2015) identifies several factors make this particularly problematic in
oncology. For example, the names of many chemotherapy agents end in “nib”.
The third theme in
the ISMP Canada report is lack of safe handling procedures. Remember - many
chemotherapy agents are hazardous substances and precautions must be taken to
prevent exposure of healthcare workers, caretakers, etc. to these substances.
Prominent warning labels should be used and standardized procedures for
handling these medications are needed. The latter would include things like
designating who can prepare, dispense, or administer such agents and
appropriate precautions such as use of personal protective equipment and use of
designated devices. An example given was failure to properly clean a tray that
had been used for filling a hydroxyurea prescription before using the tray to
fill another prescription. They also note use of automated packaging
technologies, particularly in the long-term care setting, may inadvertently
contaminate multiple medications if the packing device is exposed to hazardous
chemotherapy agents.
ISMP Canada also
cautions hospitals to be wary of allowing patients to use their own supply of
medications when hospitalized because this may bypass many of the safety
interventions put in place to prevent such incidents.
Many of these issues
were identified in a classic article on medication errors related to oral
chemotherapy (Weingart
2010). Weingart and colleagues identified issues with oral chemotherapy
from a variety of sources. They identified over 500 such errors, including 99
actual adverse drug events. While many of the remaining events were near-misses
they did provide the opportunity for patient harm and thus were helpful in
identifying potential vulnerabilities. The most common complications with harm
involved bone marrow suppression or compromise of treatment efficacy. The
errors identified occurred in every stage of the medication use process and
involved oncologists, pharmacists, nurses, patients, and patients’ families or
friends. Wrong dose errors were most frequent but wrong drug errors also
occurred. One particularly salient problem was supplying the wrong number of
days. As noted above, chemotherapy regimens may be very complex and involve
cycles and different dosing at different times so this can result in confusion
for patients, pharmacists, and other healthcare workers. Actually, last year
ISMP provided an example of this in an unfortunate incident where a woman being
treated for a brain tumor received an overdose of lomustine (ISMP
2014). A mail order pharmacy dispensed a 3-dose supply of lomustine rather
than a single dose. The patient, who had been used to taking her previous
chemotherapy as a single dose, took the whole supply of lomustine as a single
dose before she realized the mistake. This led to a protracted painful death
with bone marrow suppression. Ironically, this was not the first such case.
ISMP noted multiple prior similar errors. ISMP recommended that prescribers
always specify a single dose when prescribing lomustine and specifically
provide both verbal counselling and written instructions for the patient.
Pharmacies and pharmacists should program alerts into their computer systems to
specify “single dose only” (ISMP also suggests avoiding mail order pharmacies
for such drugs since they often provide multi-month supplies and payors should
only pay for single doses of such drugs) and do appropriate counselling of
patients. They also note the FDA and manufacturers need to ensure that warnings
appear in a much more obvious way for such drugs.
Weingart et al. also
noted several cases where health literacy issues and language barriers probably
played a role. The wrong drug errors were often due to look-alike
sound-alike (LASA) confusion and were likely to involve chemotherapy agents
being given to patients who did not have cancer. They also identified missed
dose errors, errors related to confusing or ambiguous instructions, incomplete
prescriptions, and others.
Importantly, the
Weingart study demonstrated that the types of errors identified varied
significantly by the source of the reports, i.e. reports from hospital sources
differed from those from pharmacy sources, and so on.
One recent article
described the team approach at Memorial Sloan-Kettering to preventing oral
chemotherapy agent errors (O’Rourke
2015). Among common causes of chemotherapy errors they noted ones that may
affect any medication, such as miscommunicated verbal orders, interruptions, LASA issues, use of abbreviations, packaging/labeling
issues, legibility/fax issues, and drug shortages. They again highlighted the
issue of taking daily doses when a different regimen was intended and provide
examples, including the ones regarding methotrexate and lomustine that we
discussed earlier. But they also point out that many chemotherapy agents have
interactions with medications patients are taking for other medical conditions
and provide a list of selected interactions. They stress a team approach and
use of standardized protocols and processes. They also stress one of our
frequent recommendations (“stories not statistics”), noting that the
presentation of actual events is a powerful tool in educating staff about
possible errors.
One particular
concern with chemotherapy agents is dose calculation. Doses for some
drugs are based upon the patient’s weight or body surface area (BSA), the
latter requiring knowledge of the patient’s height. Any time we are dealing
with dose calculations the issue of decimal points arises. In our September 9,
2008 Patient Safety Tip of the Week “Less
is More…and Do You Really Need that Decimal?” we discussed whether numbers should
ever follow a decimal point. They may be important in certain circumstances
(eg. for a dose of 0.3 mg or 2.7 mg of a drug you would avoid rounding).
However, at higher doses they become much less relevant and rounding of the
dose is appropriate. For example, let’s say you performed a calculation and the
result was a recommended dose of a drug is 72.2 mg. Is there really a difference if
the patient gets 72 mg or 72.2 mg of most drugs? Yet ordering the latter dosage
increases the risk that the decimal point may not be seen or not input into a
computer or missed in a faxed order and the patient gets a 10x overdose. So we
strongly recommend that in writing medication orders one specifically decides
whether such fractional doses are important or merely place the patient at
increased risk of an error.
Speaking of weight-based and BSA-based dose calculations, making
the ECRI Institute Top 10 list for patient safety concerns for 2015 were
medication errors related to pounds and kilograms (ECRI 2015).
Calculations done mixing up pounds and kilograms can result in roughly a
two-fold error in calculated dose. Especially for oncology drugs that have a
very narrow therapeutic index and safety margin, such errors could easily
result in toxicity or in lack of efficacy, depending on which direction the
error is made in.
ECRI recommends doing away with scales that measure in
pounds in healthcare settings and requiring all weights be input into EHR’s
using only kilograms. Note that one could still erroneously enter a value in
pounds in an EHR field but clinical decision support tools can at least compare
a value to an expected weight and flag those falling outside that range. But
it’s not failsafe. A PPSA advisory (PPSA
2009) on the importance of accurate weights in avoiding medication errors
did not list chemotherapy agents among their most frequently reported
medication errors but nevertheless had important recommendations. PPSA also recommends
including the date of the weight. That might be particularly relevant to
oncology patients who may have had significant weight change since the last
recorded weight.
Both the ISMP and
Memorial Sloan-Kettering experiences look to use of computerized tools to help
prevent such errors. Using CPOE (computerized physician order entry) or
e-prescribing systems has the advantage of automating dose calculations, thereby
reducing some potential errors. They also provide easy access to standardized
order sets. They also have the advantage of being able to use clinical decision
support tools for generating alerts for excessive doses, etc.
Partners Healthcare
and the Dana Farber Cancer Institute built a system for electronically prescribing
oral chemotherapy agents (Weingart
2012). That system provided support for calculating doses based upon
patient weight or body surface area and even calculations for toxicity-related
dose adjustments. It also included a field for the primary cancer diagnosis,
which could either be imported from other fields in the EHR or input by the
ordering clinician, and another field for indicating reason for the
chemotherapy agent (eg. curative, adjuvant, palliative). Clinicians could also
input items such as the cycle number or a clinical trial number. The system
also had the other capabilities we expect in e-prescribing systems like allergy
alerts, drug-drug interaction alerts, renal dose warnings, etc. The system was
well-accepted by clinicians. The reason for the chemotherapy agent was seldom
entered. The primary cancer diagnosis was entered in about half the cases,
perhaps because that diagnosis was often imported from other fields. There was
also a free-text field where prescribers could enter things like clarifying the
number of tablets of different strengths that should be taken together. Alerts
were triggered in 5.9% of prescriptions but most were actually not helpful (the
dose-limit for some drugs had been set below the currently used standard).
Overall, 6 drugs accounted for 83% of the prescriptions, likely reflecting the
patient population served by the study hospitals and practices. They learned
some valuable lessons for building such systems. One was that use of the
diagnosis and reason/intent field was suboptimal. Clinicians also need easier
ways to indicate things like cycle number, days per cycle, nontreatment days,
and instructions for combining tablets of different strength. They also learned
that dose-limit alerts need to be updated regularly to keep up with current
practice standards.
Another study compared non-intercepted dose errors for
chemotherapy agents in paper-based vs. computer-based systems (Mattsson 2015).
They found an overall risk of a
prescription dose error of 1.73 per 100 prescriptions (1.60 for CPOE and 1.84
errors per 100 prescriptions, a nonsignificant difference). Fifteen different
types of errors and four potential risk factors were identified. They found the
computer system reduced the risk of calculation errors but introduced other
errors. The Mattsson and Weingart studies highlight the potential of
computerized systems to reduce errors but both show we have a long way to go in
reaching that goal.
A handy monograph on
preventing chemotherapy errors (Kloth
2010) has a great list of the “Do’s” and Do Not’s” of prescribing. Many of
the “Do Not’s” apply to all prescribing, not just chemotherapy agents (eg.
abbreviations, trailing zeros, lack of zero preceding decimals, etc.). But a
few are especially important when chemotherapy drugs are used. Kloth recommends
never using verbal orders for chemotherapy. Also describing “vials” should not
be done since vials of chemotherapy agents come in so many sizes and
concentrations. He also cautions against using outdated laboratory results for
those agents that may be affected by things like renal or hepatic function.
Among the “Do’s” is always writing the full name (preferably the generic name)
of the drug. For doses greater than 5 mg use rounding so no digits appear after
a decimal point (see above). He also emphasizes the importance of double checks.
In our October 16, 2012 Patient Safety Tip of the Week “What
is the Evidence on Double Checks?” we concluded that double checks remain a relatively weak safety
intervention and they are prone to errors but, done correctly, the independent
double check probably does provide an additional element to our defenses
against errors. Particularly for high-alert medications, such as chemotherapy
agents, doing independent double checks at multiple stages makes a lot of
sense.
Our prior columns related to chemotherapy safety:
- September 11, 2007 “Root
Cause Analysis of Chemotherapy Overdose”
- April 2010 “Medication
Incidents Related to Cancer Chemotherapy”
- April 6, 2010 “Cancer
Chemotherapy Accidents”
- July 2010 “Methotrexate
Overdose Due to Prescribing Error”
- July 2011 “More
Problems with Methotrexate”
References:
ISMP Canada. Analysis of Incidents Involving Oral
Chemotherapy Agents. ISMP Canada Safety Bulletin 2015; 15(4): 1-4, April 22,
2015
http://www.ismp-canada.org/download/safetyBulletins/2015/ISMPCSB2015-04_OralChemotherapyAgents.pdf
ISMP (Institute for Safe Medication Practices). ISMP’s List
of Confused Drug Names. Updated February 2015
http://www.ismp.org/Tools/confuseddrugnames.pdf
O’Rourke K. Preventing Oral Chemo Errors: A Team Approach.
Pharmacy Practice News 2015; 42: 1-4 March 2015
Weingart SN, Toro J, Spencer J, et al. Medication errors
involving oral chemotherapy. Cancer 2010; 116(10): 2455-2464
http://onlinelibrary.wiley.com/doi/10.1002/cncr.25027/abstract
ISMP (Institute for Safe Medication Practices). With oral
chemotherapy, we simply must do better! ISMP Medication Safety Alert! Acute
Care Edition. July 17, 2014
https://www.ismp.org/newsletters/acutecare/showarticle.aspx?id=84
ECRI Institute. Top 10 Patient Safety Concerns for 2015
https://www.ecri.org/Pages/Top-10-Patient-Safety-Concerns.aspx
PPSA (Pennsylvania Patient Safety Authority). Medication
Errors: Significance of Accurate Patient Weights. Pa Patient Saf Advis 2009;
6(1): 10-15
http://patientsafetyauthority.org/ADVISORIES/AdvisoryLibrary/2009/Mar6%281%29/Pages/10.aspx
Weingart SN; Mattsson T; Zhu J; Shulman LN; Hassett M. Improving
electronic oral chemotherapy prescription: can we build a safer system? Journal
of oncology practice/American Society of Clinical Oncology 2012; 8(6): e168-73,
2012 Nov
http://jop.ascopubs.org/content/8/6/e168.full.pdf+html?sid=b1353905-08c7-46d9-9e91-12517e009862
Mattsson TO, Holm B, Michelsen H, et al. Non-intercepted
dose errors in prescribing antineoplastic treatment: a prospective, comparative
cohort study. Ann Oncol 2015; 26(5): 981-986 First
published online: January 28, 2015
http://annonc.oxfordjournals.org/content/26/5/981.abstract
Kloth DD. Guide to the Prevention of Chemotherapy Medication
Errors. Second Edition. New York: McMahon Publishing 2010
http://www.clinicaloncology.com/download/pg1012_mederrors_conc0610_WM.pdf
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