Intended for healthcare professionals

Rapid response to:


Doctors warned to be wary of new drugs

BMJ 2002; 324 doi: (Published 11 May 2002) Cite this as: BMJ 2002;324:1113

Rapid Response:


The physician is responsible for prescribing the right medication at
effective dose potency with minimal risk to the patient. The more potent
the medication, the more potential the risk to inducing harm from
prescription dose. Some new medication is predisposed to create dose-
induced risk more than others. Individual patient differences add other
factors for increasing the risk of reaction to dose-induced harm. With the
massive expanding lists new drugs with the potential to impose harm
further exacerbates risk for a poorly-predicted reaction.

-Patient education by the medical office staff insures higher compliance
and exact prescription use reducing the risk of overdose or misuse

-Checks and balances for review of prescription and dose reduces risk
of overdose resulting in medical error

-Clinical pharmacy services and hospital pharmacy staffing variables
are associated with reducing medication error rates

-Preclinical prescription screening tools for reducing risk of excess
dose for some prescription drugs may be limited to lethal dose 50% [LD50]
from animal studies

The practice of modern medicine has limited power remarkably
dependant upon a conservative approach for generating good and reducing
the risks of additional harm. [1] Clinicians are human; no physician has
yet to report a lifetime of error-free medicine. Verification of dose and
schedule are critical steps in the practice of medicine. Less than optimal
dosing can result in reduced efficacy, and an overdose can cause profound
toxicity and death. A model example is presented in the systematic format
for reviewing chemotherapy orders reducing the potential for medication
errors. Patient safety is further enhanced by careful verification of
dosages and schedules. [2]

One-third of the disciplinary actions against physicians in 1990
involved prescriptions for controlled or high abuse drugs. Problems
involving the prescribing of controlled medications may occur because of
overdose dependence or use by known drug abusers. A common problem facing
the physician is the identification of potential overdose victims and
addicted patients. [3]

Antidepressant drugs are among the most common drugs involved in
fatal poisoning and large variations between antidepressant drugs have
been noted. There are humane and practical reasons for developing a pre-
clinical indicator of toxicity in overdose for this rapidly expanding
group of drugs. Buckley & McManus examined what preventative overdose
measures. They concluded the best current pre-clinical indicator of fatal
toxicity in humans is the LD50 from animal studies. [4] What the lethal
dose is for 50% of test animal subjects presents a wide margin for error
for a small but undetermined percent of prescription-dosed human subjects.

Overdose of prescription drugs typically occurs through two venues,
patient abuse and/or dose prescription exceeding patient tolerance. The
patients may either accidentally or purposely overdose a medication.
Conservative standard prescriptions may occasionally exceed a patient's
physical tolerance. During one study of 836 patients who were diagnosed
for lung obstructive chronic disease, cirrhosis, gastrointestinal
hemorrhage and cancer, 6,308 drug prescriptions were written. An "Expert
Drug System" was employed to evaluate these prescriptions and dose
according to patient characteristics, such as age, weight, height, sex,
renal function and liver function. The system recommends the correct dose,
detects interactions and adverse effects and makes suggestions in
pregnancy and lactation. The expert system detected 458 overdoses and 33
underdoses, mainly in antibiotics and antiulcer drugs, and 1,722
interactions. The frequency of drug overdose and underdosages in patients
admitted in this university hospital is relatively high. [5]

Copenhagen University Hospital evaluated 170 prescriptions in a
project at Copenhagen University Hospital Pharmacy. Prescriptions were
collected at two private pharmacies in Copenhagen during a two-week period
in October 1995. The prescriptions contained an average of 1.5 errors and
89% had errors with only 11% without fault. The three most frequent errors
of omission were code of department, inadequate identification of the
physician and indications of use. [6] Were these prescriptive dose
misdirections limited only to these 2 European hospitals examined or is
this a commonly widespread phenomena? Are hospitals and health systems in
the USA using the best practices that are available today to order,
dispense, and monitor medications for patients?

The direct relationships and associations among clinical pharmacy
services, pharmacist staffing, and medication errors in United States
hospitals were evaluated. A database was constructed from the 1992
National Clinical Pharmacy Services database. A total of 429,827
medication errors were evaluated from 1081 hospitals. Medication errors
occurred in 5.22% of patients admitted to these hospitals each year.
Hospitals experienced a medication error every 22.04 hours (1 in every
19.13 admissions). These findings suggest that at minimum, 90,895 patients
annually were harmed by medication errors in American general medical-
surgical hospitals. Factors associated with increased medication
errors/occupied bed/year were drug-use evaluation increased staffing of
hospital pharmacy administrators/occupied bed, and increased staffing of
dispensing pharmacists/occupied bed. Factors associated with decreased
medication errors/occupied bed/year were presence of a drug information
service, pharmacist-provided adverse drug reaction management, pharmacist-
provided drug protocol management, pharmacist participation on medical
rounds, pharmacist-provided admission histories, and increased staffing of
clinical pharmacists/occupied bed. As staffing increased for clinical
pharmacists/occupied bed from the 10th percentile to the 90th percentile,
medication errors decreased from 700.98 +/- 601.42 to 245.09 +/-
197.38/hospital/year, a decrease of 286%. Specific increases or decreases
in yearly medication errors associated with these clinical pharmacy
services in the 1081 study hospitals were drug-use evaluation (21,372 more
medication errors), drug information services (26,738 fewer medication
errors), adverse drug reaction management (44,803 fewer medication
errors), drug protocol management (90,019 fewer medication errors),
medical round participation (42,859 fewer medication errors), and
medication admission histories (17,638 fewer medication errors). Overall,
clinical pharmacy services and hospital pharmacy staffing variables were
associated with medication error rates. [7] Though such results should
help hospitals reduce the number of medication errors that occur each
year, in the meantime, one medical error may result in needless loss of a
human life.

Studies using physician implicit review have suggested that the
number of deaths due to medical errors in USA hospitals is also too high.
Reviewer estimates of whether deaths could have been prevented by optimal
care and of the probability that patients would have lived to discharge or
for 3 months or more if care had been optimal were rated. Similar to
previous studies, almost a quarter (22.7%) of active-care patient deaths
were rated as at least possibly preventable by optimal care, with 6.0%
rated as probably or definitely preventable. They estimated that the
percentage of patients who would have left the hospital alive had optimal
care been provided was 6.0%. However, after considering 3-month prognosis
and adjusting for the variability and skewness of reviewers' ratings,
clinicians reestimated that only 0.5% of patients who died would have
lived 3 months or more in good cognitive health if care had been optimal,
representing roughly 1 patient per 10,000 admissions to the study
hospitals. [8]

Though 9,999 persons survive standard medical treatment but one life
is errantly lost, that is one life that otherwise should have been saved.
When the present order of medical staffing is increased in order to reduce
case overload, with responsible 2nd and 3rd party prescription-treatment
dose review prior to dose application, the consequences of risk for
medical error from higher dose prescriptions may be decreased.

In my opinion, we need more people involved on the "treatment team"
in order to resolve medical prescription error. George Dunea summarized,
"Diagnostic mistakes could further be avoided by recognizing the
underlying factors that distract attention, such as boredom, frustration,
anger, work overload, or environmental factors, such as noise or heat.
Errors may be due to poor skills, faulty judgment, flawed data, or bias,
haste, not seeing the patient as a whole, and not failure to spend the
time to diagnose from prescribing without complete knowledge. Unwanted
outcomes may also result from leaving major decisions in the hands of
inexperienced junior staff; these often also represent system failures and
should be corrected by better deployment of medical personnel. [9] A very
good example worthy of review is finding others to lighten the load by
numerically increasing professional assistance for the "treatment team."
Nurse Practitioners assigned to the medical staff were observed to
effectively expand treatment capacity and reduce the workload's impact of
risk to create a medical error. [10] The new drugs require study in depth
review before an effective dose-effect is accurately applied. This calls
to question for a published drug review by an independant physician's
group which details dose outcome to the general patient population to whom
the drug may help or may be contraindicated.


[1] Smith R. Why are doctors so unhappy? BMJ 2001;322:1073-1074.

[2] Schulmeister L. Preventing chemotherapy dose and schedule errors.
Clin J Oncol Nurs. 1997 Jul;1(3):79-85.

[3] Voth EA, Dupont RL, Voth HM. Responsible prescribing of
controlled substances. Am Fam Physician. 1991 Nov;44(5):1673-8.

[4] Buckley NA, McManus PR. Can the fatal toxicity of antidepressant
drugs be predicted with pharmacological and toxicological data? Drug Saf.
1998 May;18(5):369-81.

[5] Codina C, Corominas N, Roca M, Tuset M, del Cacho E, Soy D, Gomez
B, Perez M, Masso J, Ribas J. [Comparative study of an expert system
application in the prescription of medications] Med Clin (Barc). 1997 Oct

[6] Andersen SO, Beurling C. [Prescriptions, prescription-writing
errors and patient safety] Ugeskr Laeger. 1997 Mar 3;159(10):1454-8.

[7] Hayward RA, Hofer TP. Estimating hospital deaths due to medical
errors: preventability is in the eye of the reviewer. JAMA. 2001 Jul

[8] Bond CA, Raehl CL, Franke T. Clinical pharmacy services, hospital
pharmacy staffing, and medication errors in United States hospitals.
Pharmacotherapy. 2002 Feb;22(2):134-47.

[9] Dunea G, Views and Reviews, Soundings, Mistakes. BMJ
1998;316:1026 ( 28 March )

[10] Horrocks S, Anderson E, Salisbury C, Systematic review of
whether nurse practitioners working in primary care can provide equivalent
care to doctors. BMJ 2002; 324: 819-823.

Bill Misner, Ph.D. <>
The author has no competing interests in this subject area.

Competing interests: No competing interests

11 May 2002
Bill D. Misner Ph.D.
R & D Director, ECAPS Inc.
Spokane, Washington, 99205, USA