This article will cover the following knowledge areas related to medication safety:

• Error prevention strategies for data entry (e.g., prescription or medication order to correct patient)
• Patient package insert and medication guide requirements (e.g., special directions and precautions)
• Identify issues that require pharmacist intervention (e.g., DUR, ADE, OTC recommendation, therapeutic substitution, misuse, missed dose)
• Look-alike/sound-alike medications
• High-alert/risk medications
• Common safety strategies (e.g., tall man lettering, separating inventory, leading and trailing zeros, limit use of error prone abbreviations)

Terminology

To get started in this chapter, there are some terms that should be defined.

medication errors - A medication error is any incorrect or wrongful administration of a medication, such as a mistake in dosage or route of administration, failure to prescribe or administer the correct drug or formulation for a particular disease or condition, use of outdated drugs, failure to observe the correct time for administration of the drug, or lack of awareness of adverse effects of certain drug combinations.

mondegreen - A mondegreen is the mishearing or misinterpretation of a phrase as a result of near-homophony, in a way that gives it an unintended meaning.

risk evaluation and mitigation strategy - A risk evaluation and mitigation strategy (REMS) is a plan to manage a known or potential serious risk associated with a drug or biological product.

prospective drug utilization review - Prospective drug utilization review (ProDUR) require state Medicaid provider pharmacists to review Medicaid recipients' entire drug profile before filling their prescription(s). The ProDUR is intended to detect potential drug therapy problems.

MedWatch - MedWatch is the Food and Drug Administration’s reporting system for an adverse event.

adverse drug event - An adverse drug event (ADE) is any undesirable experience temporally associated with the use of a medication.

Vaccine Adverse Event Reporting System - Vaccine Adverse Event Reporting System (VAERS) is a post-marketing safety surveillance program, collecting information about adverse events (possible side effects) that occur after administration of vaccines.

Medication errors

A medication error is any incorrect or wrongful administration of a medication, such as a mistake in dosage or route of administration, failure to prescribe or administer the correct drug or formulation for a particular disease or condition, use of outdated drugs, failure to observe the correct time for administration of the drug, or lack of awareness of adverse effects of certain drug combinations. Causes of medication error may include difficulty in reading handwritten orders, confusion about different drugs with similar names, and lack of information about a patient's drug allergies or sensitivities.

The National Coordinating Council for Medication Error Reporting and Prevention (NCC MERP) has organized medication errors into four major groupings encompassing a total of nine categories (categories A through I):

• No Error
  • Category A: Circumstances or events that have the capacity to cause error
• Error, No Harm
  • Category B: An error occurred but the error did not reach the patient
  • Category C: An error occurred that reached the patient but did not cause patient harm
  • Category D: An error occurred that reached the patient and required monitoring to confirm that it resulted in no harm to the patient and/or required intervention to preclude harm
• Error, Harm
  • Category E: An error occurred that may have contributed to or resulted in temporary harm to the patient and required intervention
  • Category F: An error occurred that may have contributed to or resulted in temporary harm to the patient and required initial or prolonged hospitalization
  • Category G: An error occurred that may have contributed to or resulted in permanent patient harm
  • Category H: An error occurred that required intervention necessary to sustain life
• Error, Death
  • Category I: An error occurred that may have contributed to or resulted in the patient’s death

The following are some sobering facts related to medication errors.

• The Institute of Medicine (IOM) estimates that up to 98,000 people die annually in the United States from medical errors and does not include those seriously injured.
• To go further, a study conducted by The Leapfrog Group estimates that 7,000 of these deaths are due to medication errors.
• According to Franklin et al, 1.5 million people in the United States are sickened, injured, or killed each year due to prescription errors.

Common error sources

According to a study of prescription errors conducted by MEDMARX and released in 2005, the following is a quick breakdown about the causes of these errors:

• Performance deficit (failure to act in accordance with education and training)- 38%
• Procedure/protocol not followed - 17%
• Transcription inaccurate/omitted - 13%
• Computer entry - 12%
• Documentation lacking/inaccurate - 12%
• Knowledge deficit - 10%
• Communication - 9%

Error prone abbreviations

There are a number of abbreviations and dose designations that can be misinterpreted. Below is a list of some of the more commonly misinterpreted abbreviations and dose designations.

μg - microgram - mistaken as "mg" - to avoid confusion use "mcg"
U or u - unit - mistaken for "0" (zero), the number "4" (four) or "cc" - to avoid confusion write "unit"
IU - International Unit - mistaken for "IV" (intravenous) or the number "10" (ten) - to avoid confusion write "International Unit"
Q.D., QD, q.d., or qd - daily - mistaken for qod (every other day) or "qid" (four times a day) - to avoid confusion write "Daily"
Q.O.D., QOD, q.o.d., or qod - every other day - the period after the Q mistaken for "I" and the "O" mistaken for "I" causing confusion with "qid" - to avoid confusion write "every other day"
q.i.d., or qid - four times a day - the "I" may be missed or mistaken for a "." or a "O" causing confusion with "qd" and "qod" - to avoid confusion write "four times a day"
TIW or tiw - three times a week - misinterpreted as twice a week - to avoid confusion write "three times a week" or list the specific days
Trailing zero (X.0 mg) - means X mg - the decimal point may be missed and read as "X0 mg" - to avoid confusion don't use a trailing zero
Lack of leading zero (.X mg) - means 0.X mg - Without a leading zero, the decimal can be missed causing "X mg" to be dispensed - to avoid confusion write "0.X mg"
MS - Can mean morphine sulfate or magnesium sulfate and therefore can be misinterpreted - to avoid confusion write "morphine sulfate" or "magnesium sulfate"
MSO4 and MgSO4 - morphine sulfate and magnesium sulfate - they can be confused for one another - to avoid confusion write "morphine sulfate" or "magnesium sulfate"

Look-alike/sound-alike medications

A number of medications have names with similar spellings (hydroxyzine and hydralazine), similar appearance (captopril and carvedilol are both available as small round white tablets), and some medication names can be misheard for each other (Doribax and Zovirax are nearly homophones). A modern term for this last category is a mondegreen. Barcoding technologies and tallman lettering are two of the more common strategies used to overcome these challenges and are discussed further later in this chapter.

High-alert/risk medications

High-alert medications are drugs that bear a heightened risk of causing significant patient harm when they are used in error. Although mistakes may or may not be more common with these drugs, the consequences of an error are clearly more devastating to patients. The Institute for Safe Medication Practice (ISMP) has assembled a list to identify which medications require special safeguards to reduce the risk of errors. This may include strategies such as standardizing the ordering, storage, preparation, and administration of these products; improving access to information about these drugs; limiting access to high-alert medications; using auxiliary labels and automated alerts; and employing redundancies such as automated or independent double-checks when necessary. (Note: manual independent double-checks are not always the optimal error-reduction strategy and may not be practical for all of the medications on the list).

Classes/categories of high-alert medications

The following list of classes/categories of high-alert medications come form the ISMP.

• adrenergic agonists, IV (e.g., EPINEPHrine, phenylephrine, norepinephrine)
• adrenergic antagonists, IV (e.g., propranolol, metoprolol, labetalol)
• anesthetic agents, general, inhaled and IV (e.g., propofol, ketamine)
• antiarrhythmics, IV (e.g., lidocaine, amiodarone)
• antithrombotic agents, including:
  • anticoagulants (e.g., warfarin, low-molecular-weight heparin, IV unfractionated heparin)
  • Factor Xa inhibitors (e.g., fondaparinux)
  • direct thrombin inhibitors (e.g., argatroban, bivalirudin, dabigatran etexilate, lepirudin)
  • thrombolytics (e.g., alteplase, reteplase, tenecteplase)
  • glycoprotein IIb/IIIa inhibitors (e.g., eptifibatide)
• cardioplegic solutions
• chemotherapeutic agents, parenteral and oral
• dextrose, hypertonic, 20% or greater
• dialysis solutions, peritoneal and hemodialysis
• epidural or intrathecal medications
• hypoglycemics, oral
• inotropic medications, IV (e.g., digoxin, milrinone)
• insulin, subcutaneous and IV
• liposomal forms of drugs (e.g., liposomal amphotericin B) and conventional counterparts (e.g., amphotericin B desoxycholate)
• moderate sedation agents, IV (e.g., dexmedetomidine, midazolam)
• moderate sedation agents, oral, for children (e.g., chloral hydrate)
• narcotics/opioids including:
  • IV
  • transdermal
  • oral (including liquid concentrates, immediate and sustained-release formulations)
• neuromuscular blocking agents (e.g., succinylcholine, rocuronium, vecuronium)
• parenteral nutrition preparations
• radiocontrast agents, IV
• sterile water for injection, inhalation, and irrigation (excluding pour bottles) in containers of 100 mL or more
• sodium chloride for injection, hypertonic, greater than 0.9% concentration

Specific high-alert medications

The following list of specific high-alert medications come form the ISMP.

• epoprostenol (Flolan), IV
• magnesium sulfate injection
• methotrexate, oral, non-oncologic use
• opium tincture
• oxytocin, IV
• nitroprusside sodium for injection
• potassium chloride for injection concentrate
• potassium phosphates injection
• promethazine, IV
• vasopressin, IV or intraosseous

Error prevention strategies

The medical profession has a responsibility to provide safe and effective health care and that includes reducing medication misadventures. There are a broad array of error prevention tools out there including using the five rights (some times also expanded to the seven rights), using extra precautions with respect to high-alert medications, adopting system wide use of Tallman lettering, avoiding error prone abbreviations, using barcoding technology, and even just separating inventory. Providing infiormation to patients through medications guides, patient counselling, and drug utilization reviews (DURs) improves compliance and decreses errors as well.

Five rights

There are five rights commonly associated with medication administration to help improve patient safety.

The five rights of medication administration are:

• Right patient - Most important of all, do you have the right patient? Verify the patient information. Check the wrist band. Ask the patient to tell you his name and date of birth. If he can't tell you, does he know his physician's name? Is there a family member present to verify identification? Never use the room and bed number as the sole means of identification.
• Right medication - Check the label on the bottle, bubble pack or other packaging. Also be aware of the generic name of the medication ordered in case of product substitution.
• Right dose - Make sure that the quantity and strength of the medication matches what was ordered.
• Right time - Many medications are time sensitive. Be sure to give the medication at the proper time and at the proper interval.
• Right route - Some medications have various routes that they could be administered, be sure that the medication you have is appropriate for the route it needs to be administered.

Many institutions have started including additional rights which vary from facility to facility. These additional rights most typically include:

• Right technique - Be sure you are using the correct technique to administer the medication. Typically something intended for intramuscular injection will not achieve the desired effect if given intravenously.
• Right chart information - In an institutional setting there will typically be a patient chart that you can verify all your information against in order to double-check everything else.
• Right documentation - Proper documentation of information will help the other health professionals provide better care for the patient when they look over the patient's chart/medication administration record.
• Right attitude - Patients and their family members will typically be much more compliant and helpful if the medical care givers display an appropriate attitude.

Tallman lettering

Tallman lettering (or Tall Man lettering) is the practice of writing part of a drug's name in upper case letters to help distinguish sound-alike, look-alike drugs from one another in order to avoid medication errors. Several studies have shown that highlighting sections of drug names using tallman letters can help distinguish similar drug names, making them less prone to mix-ups. ISMP, FDA, The Joint Commission, and other safety-conscious organizations have promoted the use of tallman letters as one means of reducing confusion between similar drug names.

Below are two lists with recommendations for the use of tallman lettering. The first list is of FDA-approved established drug names with recommended tallman letters, which were first identified during the FDA Name Differentiation Project. The second list is of additional drug names with recommendations from ISMP regarding the use and placement of tallman letters.

FDA's list

The following is a Food and Drug Administration approved list of generic drug names with tallman letters. The medications have been grouped to emphasize which medications are commonly mistaken by having sound sound-alike, look-alike names.

Established Name	Recommended Name
acetohexamide acetazolamide	acetaHEXAMIDE acetaZOLAMIDE
bupropion buspirone	buPROPion busPIRone
chlorpromazine chlorpropamide	chlorproMAZINE chlorproPAMIDE
clomiphene clomipramine	clomiPHENE clomiPRAMINE
cyclosporine cycloserine	cycloSPORINE cycloSERINE
daunorubicin doxorubicin	DAUNOrubicin DOXOrubicin
dimenhydrinate diphenhydramine	dimenhyDRINATE diphenhydrAMINE
dobutamine dopamine	DOBUTamine DOPamine
glipizide glyburide	glipiZIDE glyBURIDE
hydralazine hydromorphone hydroxyzine	hydrALAZINE HYDROmorphone hydrOXYzine
medroxyprogesterone methylprednisolone methyltestosterone mitoxantrone	medroxyPROGESTERone methylPREDNISolone methylTESTOSTERone mitoXANTRONE
nicardipine nifedipine	niCARdipine NIFEdipine
prednisone prednisolone	predniSONE prednisoLONE
risperidone ropinirole	risperiDONE rOPINIRole
sulfadiazine sulfisoxazole	sulfADIAZINE sulfiSOXAZOLE
tolazamide tolbutamide	TOLAZamide TOLBUTamide
vinblastine vincristine	vinBLAStine vinCRIStine

ISMP's list

The following is an Institute for Safe Medication Practices recommended list of drug names with tallman letters. The medications have been grouped to emphasize which medications are commonly mistaken by having sound sound-alike, look-alike names.

Established Name	Recommended Name
alprazolam lorazepam	ALPRAZolam LORazepam
amiloride amlodipine	aMILoride amLODIPine
aripirazole rabeprazole	ARIPiprazole RABEprazole
Avinza Invanz	AVINza INVanz
azacitidine azathioprine	azaCITIDine azaTHIOprine
carbamazepine oxcarbazepine	carBAMazepine OXcarbazepine
carboplatin cisplatin	CARBOplatin CISplatin
cefazolin cefotetan cefoxitin ceftazidime ceftriaxone	ceFAZolin cefoTEtan cefOXitin cefTAZidime cefTRIAXone
Celebrex Celexa	CeleBREX CeleXA
chlordiazepoxide chlopromazine	chlodiazePOXIDE chlorproMAZINE
clonazepam clonidine clozapine Klonopin lorazepam	clonazePAM cloNIDine cloZAPine KlonoPIN LORazepam
dactinomycin daptomycin	DACTINomycin DAPTOmycin
docetaxel paclitaxel	DOCEtaxel PACLitaxel
doxorubicin idarubicin	DOXOrubicin IDArubicin
duloxetine fluoxetine paroxetine	DULoxetine FLUoxetine PARoxetine
ephedrine epinephrine	ePHEDrine EPINEPHrine
fentanyl sufentanil	fentaNYL SUFentanil
flavoxate fluphenazine fluvoxamine	flavoxATE fluPHENAZine fluvoxaMINE
guaifenesin guanfacine	guaiFENesin guanFACINE
Humalog Humulin	HomaLOG HumuLIN
hydrocodone oxycodone Oxycontin	HYDROcodone oxyCODONE OxyCONTIN
hydromorphone morphine	HYDROmorphone morphine
infliximab rituximab	inFLIXimab riTUXimab
isotretinoin tretinoin	ISOtretinoin tretinoin
Lamictal Lamisil	LaMICtal LamISIL
lamivudine lamotrigine	lamiVUDine lamoTRIgine
levetiracetam levocarnitine	levETIRAcetam levOCARNitine
metformin metronidazole	metFORMIN metroNIDAZOLE
mitomycin mitoxantrone	mitoMYcin mitoXANtrone
Nexavar Nexium	NexAVAR NexIUM
nicardipine nifedipine nimodipine	niCARdipine NIFEdipine niMODipine
Novolin Novolog	NovoLIN NovoLOG
olanzapine quetiapine	OLANZipine QUEtiapine
pemetrexed pralatrexate	PEMEtrexed PRALAtrexate
pentobarbital phenobarbital	PENTobarbital PHENobarbital
Prilosec Prozac	PriLOSEC PROzac
quinidine quinine	quiNIDine quiNINE
Risperidal risperidone ropinirole	RisperDAL risperiDONE rOPINIRole
romidepsin romiplostim	romiDEPsin romiPLOStim
Sandimmune Sandostatin	SandIMMUNE SandoSTATIN
Seroquel Sinequan	SEROquel SINEquan
sitagliptin sumatriptan zolmitriptan	sitaGLIPtin SUMAtriptan ZOLMitriptan
Solu-Cortef Solu-Medrol	Solu-CORTEF Solu-MEDROL
sorafenib sunitinib	SORAfenib SUNItinib
sulfadiazine sulfasalazine	sulfADIAZINE sulfaSALAzine
Tegretol Trental	TEGretol TRENtal
tiagabine tizanidine	tiaGABine tiZANidine
tramadol trazodone	traMADol traZODone
valacyclovir valganciclovir	valACYclovir valGANciclovir
Zyprexa Zyrtec	ZyPREXA ZyrTEC

Barcoding technologies

Barcoding technology, while common in many industries was slower to emerge in health care, although in recent years it has become much more common. Various studies have shown the potential for barcodes to reduce medication errors when dispensing medications from the pharmacy. Bedside barcode scanning, the use of barcode technology to verify a patient's identity and the medication to be administered, is a promising strategy for preventing medication errors. Also, many community pharmacies will scan the barcodes on the manufacturer's bottles to verify that the same NDC number entered in the pharmacy's computer system matches the NDC number on the drug being dispensed. Its use has been increasing in notable places such as the Veterans Affairs hospitals, University of Pittsburgh Medical Centers (UPMC), many of the major community pharmacy chains, and various hospitals throughout the United States.

Barcode medication verification at the bedside is usually implemented in conjunction with an electronic medication administration records (eMAR), allowing health care providers to automatically document the administration of drugs by means of barcode scanning. Because the eMAR imports medication orders electronically from either the computerized prescriber order entry (CPOE) or the pharmacy management software, its implementation may reduce transcription errors. Given its potential to improve medication safety, barcoding in combination with eMAR technology is being considered as a criterion for achieving “meaningful use” of health information technology and for obtaining financial incentives under the American Recovery and Reinvestment Act of 2009 in 2013.

Risk evaluation and mitigation strategies

On September 27, 2007, President George W. Bush signed into law the Food and Drug Administration Amendments Act of 2007 (FDAAA), further amending the Food, Drug, and Cosmetic Act. The FDAAA authorizes the Food and Drug Administration (FDA) to require risk evaluation and mitigation strategies (REMS) on medications if necessary to minimize the risks associated with some drugs.

The FDA has a responsibility to ensure that the benefits of a medication outweigh the potential risks of that medication. To determine this, the FDA looks at the seriousness of the disease or condition to be treated, size of the patient population, expected benefit of the drug, expected duration of treatment, and seriousness of the known or potential adverse events.

If a medication's benefits outweigh the risks associated with it, the FDA approves it. Sometimes though, the medication therapy itself still carries a lot of risks with it. In that situation, the FDA may require REMS. These risk minimization strategies go beyond FDA professional labeling. FDA can require a REMS before a drug is approved if they have determined that a REMS is necessary to ensure the benefits of the drug outweigh its risks. Also, FDA can require a REMS post-approval if they become aware of new safety information and make the determination that a REMS is necessary, again, to ensure that the benefits of the drug outweigh its risks. Elements of risk evaluation and mitigation strategies

REMS may contain any of the following elements:

• Medication Guide – Document written for patients highlighting important safety information about the drug; this document must be distributed by the pharmacist to every patient receiving the drug.
• Communication Plan – Plan to educate healthcare professionals on the safe and appropriate use of the drug and consists of tools and materials that will be disseminated to the appropriate stakeholders.
• Elements to Assure Safe Use (EASU) – These are strictly controlled systems or requirements put into place to enforce the appropriate use of a drug. Examples of EASUs include physician certification requirements in order to prescribe the drug, patient enrollment in a central registry, distribution of the drug restricted to certain specialty pharmacies, etc.
• Implementation Plan – A description of how certain EASUs will be implemented.
• Timetable for Submission of Assessments – The frequency of assessment of the REMS performance with regard to meeting the goal(s) and objective(s). FDA requires that assessments be conducted at 18 months, 3 years, and 7 years post-launch, at a minimum. Results of these evaluations must be reported to the FDA and will determine whether additional actions or modifications to the REMS program are required.

Patient package insert/medication guide requirements

A patient package insert or medication guide is a document provided along with a prescription medication to provide additional information about that drug. By providing this information to the patient there is an expectation of improved therapeutic outcomes by improving compliance and helping the patient to avoid some potential errors from medication misuse.

The Food and Drug Administration (FDA) determines the requirements for patient package inserts. Package inserts follow a standard format for every medication and include the same types of information. Different manufacturers may have different titles for their sections, however, to make them easier for the average person to read and comprehend—for example, instead of "Contraindications" the section may be headed, "Who should not take this medication?"

The first thing listed is usually the brand name and generic name of the product. The other sections are as follows:

• Clinical pharmacology - tells how the medicine works in the body, how it is absorbed and eliminated, and what its effects are likely to be at various concentrations. May also contain results of various clinical trials (studies) and/or explanations of the medication's effect on various populations (e.g. children, women, etc.).
• Indications and usage - uses (indications) for which the drug has been FDA-approved (e.g. migraines, seizures, high blood pressure). Physicians legally can and often do prescribe medicines for purposes not listed in this section (so-called "off-label uses").
• Contraindications - lists situations in which the medication should not be used, for example in patients with other medical conditions such as kidney problems or allergies
• Warnings - covers possible serious side effects that may occur
• Precautions - explains how to use the medication safely including physical impairments and drug interactions; for example "Do not drink alcohol while taking this medication" or "Do not take this medication if you are currently taking MAOI inhibitors"
• Adverse reactions - lists all side effects observed in all studies of the drug (as opposed to just the dangerous side effects which are separately listed in "Warnings" section)
• Drug abuse and dependence - provides information regarding whether prolonged use of the medication can cause physical dependence (only included if applicable)
• Overdosage - gives the results of an overdose and provides recommended action in such cases
• Dosage and administration - gives recommended dosage(s); may list more than one for different conditions or different patients (e.g., lower dosages for children)
• How supplied - explains in detail the physical characteristics of the medication including color, shape, markings, etc., and storage information (e.g., "Do not store above 95°")

Prospective drug utilization reviews

The Omnibus Budget Reconciliation Act of 1990 (OBRA-90) placed expectations on the pharmacist in how to interact with the patient. While the primary goal of OBRA-90 was to save the federal government money by improving therapeutic outcomes, the method to achieve these savings was implemented by imposing on the pharmacist counseling obligations, prospective drug utilization review (ProDUR) requirements, and record-keeping mandates.

These ProDURs require state Medicaid provider pharmacists to review Medicaid recipients' entire drug profile before filling their prescription(s). The ProDUR is intended to detect potential drug therapy problems. Computer programs can be used to assist the pharmacist in identifying potential problems. It is up to the pharmacists' professional judgment, however, as to what action to take, which could include contacting the prescriber. As part of the ProDUR, the following are areas for drug therapy problems that the pharmacist must screen:

• Therapeutic duplication
• Drug–disease contraindications
• Drug–drug interactions
• Incorrect drug dosage
• Incorrect duration of treatment
• Drug–allergy interactions
• Clinical abuse/misuse of medication

Patient counselling

When pharmacists assist patients with information on their medication use, they should include over the counter medications and dietary supplements as well. Technicians may assist in this process by identifying patients that could benefit from counseling and by gathering information, but all actual drug advice given to the patient should come from the pharmacist.

To take this a step further, the Medicare Modernization Act of 2003 allows for a pharmacist to provide (and get reimbursed for) medication management therapy services (MMTS) or an annual in-depth review of the medicare patient's medication profile. This review is to add a safety feature to prevent adverse reactions and drug interactions and to look at ways to reduce the patient cost.

Separating inventory

Separating inventory can be a useful tool for preventing errors by making harder to grab the wrong product, whether it is a concern over incorrect dosage form or an error caused by sound-alike, look-alike drugs being near each other on a shelf. Pharmacies will separate hazardous drug storage from nonhazardous drugs and internal products from external products. Many pharmacies will even take extra steps to separate sound-alike, look-alike drugs whether by physically placing them on separate shelves or through the use of automation to dispense (such as a medstation) to maintain them apart from each other.

Error reporting

The National Medication Errors Reporting Program, operated by the Institute for Safe Medication Practices (ISMP MERP), is a confidential voluntary program that provides expert analysis of system-based causes of medication errors. Through various media outlets, the Institute for Safe Medication Practices (ISMP) communicates recommendations for improving safety. ISMP MERP's voluntary reporting is available at https://www.ismp.org/orderforms/reporterrortoismp.asp

It is also useful to report medication misadventures to the Food and Drug Administration's MedWatch program at http://www.fda.gov/Safety/MedWatch/default.htm, excluding vaccines. Adverse events involving vaccines should be reported to Vaccine Adverse Event Reporting System (VAERS) at http://vaers.hhs.gov/esub/index which is ran by both the FDA and the CDC. Much like ISMP MERP, MedWatch is also voluntary, but VAERS is actually mandatory.

MedWatch

MedWatch is the Food and Drug Administration’s reporting system for an adverse event (sometime also called a sentinel event), and was founded in 1993. An adverse event is any undesirable experience temporally associated with the use of a medical product. The MedWatch system collects reports of adverse reactions and quality problems, primarily with drugs and medical devices, but also for other FDA-regulated products (e.g., dietary supplements, cosmetics, medical foods, and infant formulas). Vaccines are not covered by MedWatch, but instead entails the Vaccine Adverse Event Reporting System (VAERS). MedWatch also does not cover veterinary medicine and internet fraud.

FDA's MedWatch program offers voluntary reporting by healthcare professionals, consumers, and patients. This reporting can be conducted several different ways including a single, one-page reporting form (Form FDA 3500) that can be mailed to the address on the form or faxed to 1-800-FDA-0178, online reporting is available at https://www.accessdata.fda.gov/scripts/medwatch/medwatch-online.htm , or by phone at 1-800-FDA-1088.

The MedWatch system is intended to detect safety hazard signals for medical products. If a signal is detected, the FDA can issue medical product safety alerts or order product recalls, withdrawals, or labeling changes to protect the public health. Important safety information is disseminated to the medical community and the general public via the MedWatch web site at http://www.fda.gov/Safety/MedWatch/default.htm and the MedWatch E-list and texting service that can be subscribed to at https://public.govdelivery.com/accounts/USFDA/subscriber/new?pop=t&topic_id=USFDA_46

Raw data from the MedWatch system, together with adverse drug reaction reports from manufacturers as required by regulation, are part of a public database. Online tools that analyze the database are available for both health care consumers and professionals. The database is open enough that it was even used by journalists to investigate FDA's drug approval practice.

History of MedWatch

Before David Kessler, former FDA Commissioner, introduced MedWatch in 1993 there was not a simple mechanism in place for healthcare professionals to report adverse events associated with medications or devices directly to the FDA. Many facilities and drug manufacturers had their own complicated forms along with the FDA having separate forms for drug reactions, drug quality products problems, device quality product problems, and adverse reactions to medical devices creating a patchwork of reporting tools that were largely ignored. This was despite the post marketing surveillance required of all FDA approved medications.

Various studies conducted in the 1980's suggested that 3 to 11% of admissions could be attributed to adverse drug events and yet only about 1% of adverse events were being reported to the FDA. This means that out of 1400 hospital admissions approximately 100 would be related to adverse drug events and yet only 1 was actually being reported.

MedWatch was intended to simplify this process and the FDA was also trying to actively engage physicians, hospitals, and schools involved in health care education to use this new voluntary system. MedWatch encourages health care professionals to regard reporting as a fundamental professional and public health responsibility.

Why adverse event reporting is needed

Many health care professionals and their patients do not know that in approving medical products, including medications, biologics and devices, for sale and use that FDA does not develop or test the products itself. FDA reviews the results of laboratory, animal and human clinical testing done by companies to determine if the product they want to put on the market is safe and effective.

Because FDA's review is based on a relatively small number of users, and because variations in quality can happen in manufacturing, FDA keeps careful watch on reports of adverse experiences with products after they are marketed. If this monitoring turns up a problem that needs to be corrected, FDA can take timely actions to improve the safety of the product.

The FDA's role postmarketing surveillance when it is monitoring for safety, is a critical one because of the limitations of pre-marketing review and the controlled clinical trials used to prove the effectiveness of the product before it is approved by FDA.

For example, the reliance of FDA and the manufacturer on the controlled clinical trial to demonstrate the efficacy of a drug for its intended use in a controlled population during NDA approval is of great use. It can be determined with some certainty that the product is effective when compared with placebo and the common serious adverse reactions will be identified. But, limitations such as number of participants and subject characteristics results in uncertainties about the safety of the pharmaceutical once it is marketed and used in a wider population, over longer periods of time, in patients with co-morbidities and concomitant medications and for 'off-label' uses not previously evaluated. This is a weakness of the clinical trial as a safety identification process. Therefore, the true picture of product safety actually evolves over the years that make up a product's lifetime in the marketplace.

How MedWatch works

The FDA is interested in receiving three types of reports, first those involving suspected serious adverse events associated with drugs, either prescription or OTC, biologic products, medical devices, cosmetics and special nutritional products such as dietary supplements, medical foods and infant formulas. Second, reports, especially from pharmacists and nurses of product quality problems that might suggest manufacturing or other quality problems with drugs or devices. In addition, FDA is very interested in reports of suspected counterfeit products. Third, reports of medication and device use errors, for example, the wrong drug/wrong dose errors that may be caused by either product name confusion or confusion resulting from packaging and labeling.

This reporting can be conducted several different ways including a single, one-page reporting form (Form FDA 3500) that can be mailed to the address on the form or faxed to 1-800-FDA-0178, online reporting is available at https://www.accessdata.fda.gov/scripts/medwatch/medwatch-online.htm , or by phone at 1-800-FDA-1088. The four core elements of the report include: a reporter's name, a suspect drug or device product a narrative report of the adverse event or problem and an identifiable patient. The FDA, however, holds the identity of patients in strict confidence, protected by federal law and regulation

Patients are encouraged to take this form to their health care professional so that the report contains more detailed information when received by FDA; however, patients may submit reports directly to FDA.

Voluntary versus mandatory reporting

Often, there is a lot of concern over MedWatch's voluntary reporting, as opposed to implementing a mandatory adverse event reporting provision. The challenge would be enforcing such a provision. For a program to be mandatory there would have to be a penalty involved with noncompliance, the the FDA is concerned that penalizing individuals might deter participation rather than increase it.

An example of MedWatch's effectiveness

The story of the drug Depakote (divalproex sodium) illustrates that even after twenty years of use, new information that will improve the safe use of a medical product will be detected with the help of voluntary reports from health professionals.

In July 2000, FDA added new safety information, a black boxed warning, for Depakote after receiving multiple reports of a serious adverse event, pancreatitis, in patients taking the drug. Although the condition was listed as a possible adverse reaction when first approved in 1978, the severity of this serious condition was found to be much greater when used more widely for newer and common indications such as migraines, depression, and seizures. It was with this increased use that spontaneous reports began to be received at the FDA through it MedWatch program, prompting the new warnings to inform doctors and patients of this risk.

Even after twenty years, new information that will impact the clinical use of a medical product can be detected. Consequently, all medical products need to be continually assessed for safety.

VAERS

The Vaccine Adverse Event Reporting System is a United States program for vaccine safety, co-managed by the Centers for Disease Control and Prevention (CDC) and the Food and Drug Administration (FDA). VAERS is a post-marketing safety surveillance program, collecting information about adverse events (possible side effects) that occur after administration of vaccines.

The National Childhood Vaccine Injury Act (NCVIA) of 1986 requires health professionals and vaccine manufacturers to report to the U.S. Department of Health and Human Services (HHS) specific adverse events that occur after the administration of routinely recommended vaccines. In response to NCVIA, CDC and FDA established VAERS in 1990.

VAERS has demonstrated its public health importance by providing health scientists with signals about possible adverse events following immunization. In one instance, VAERS detected reports for intussusception over that what would be expected to occur by chance alone after the RotaShield rotavirus vaccine in 1999. Epidemiologic studies confirmed an increased risk, and these data contributed to the product's removal from the US market. In another example, VAERS determined that there may be a potential for a small increase in risk for Guillain-Barre' syndrome (GBS) after the meningococcal conjugate vaccine, Menactra. As a result of this finding, a history of GBS became a contraindication to the vaccine and further controlled studies are currently underway to research this issue.

Reporting

You are required to report all significant adverse events that occur after vaccination of adults and children, even if you are not sure whether the vaccine caused the adverse event. There are three ways to report to VAERS including online, by fax, and by mail. The online form can be found at https://vaers.hhs.gov/esub/step1 . You may also printout the VAERS form and fax it to (877) 721-0366 or mail it to VAERS, P.O. Box 1100, Rockville, MD 20849-1100. A pre-paid postage stamp is included on the back of the printed form.

Number of reports VAERS receives

VAERS receives around 30,000 reports annually, with 13% classified as serious (e.g., associated with disability, hospitalization, life-threatening illness or death) (CDC VAERS Master Search Tool, April 2, 2008). Since 1990, VAERS has received over 200,000 reports, most of which describe mild side effects such as fever. Very rarely, people experience serious adverse events following immunization. By monitoring such events, VAERS helps to identify any important new safety concerns and thereby assists in ensuring that the benefits of vaccines continue to be far greater than the risks.

Many different types of adverse events occur after vaccination. About 85-90% of the reports describe mild adverse events such as fever, local reactions, and episodes of crying or mild irritability. The remaining reports reflect serious adverse events involving life-threatening conditions, hospitalization, permanent disability, or death, which may or may not have been caused by a vaccine.

Objectives of VAERS

The primary objectives of VAERS are to:

• Detect new, unusual, or rare vaccine adverse events (VAEs);
• Monitor increases in known adverse events;
• Identify potential patient risk factors for particular types of adverse events;
• Identify vaccine lots with increased numbers or types of reported adverse events; and
• Assess the safety of newly licensed vaccines.

Limitations

VAERS has several limitations, including unverified reports, underreporting, inconsistent data quality, and absence of an unvaccinated control group for comparisons to be made against.

See also

Five rights
MedWatch
Drug recalls
Vaccine Adverse Event Reporting System
Antidote
Medication errors
High-alert medications
Barcoding technologies
Tallman lettering

References

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