Medication misadventures, medication errors and related concepts in PVG

This article is about medication errors and related concepts.

Why should I care about knowing medication errors (care enough to read an article worth 10–15 minutes, that is?)

• Medication errors are the most important and common preventable adverse drug reactions (side effects).
• MAH have obligations to reports and prevent medication errors with specific requirements by USFDA and EU regulators.
• There are specific issues on how to discuss them in RMPs and aggregate reports.
• Last and foremost, it’s a very specific highly technical stuff, but for a change (hello, EU regulators?) written in a manner using words that does not make you want to gauge your eyes out and question your life decisions!

Let’s start with medication misadventures which is a broader concept:

Medication Misadventures:

• A medication misadventure is an iatrogenic incident that is inherent to medication therapy (the necessary evil, in other words).

• Medication misadventure term includes medication errors, adverse drug reactions, and adverse drug events.

• Medication misadventures occur through omission or commission of medication administration.

• Medication misadventures always are undesirable and unexpected; they may or may not be independent of preexisting pathology; and might be due to human or system error, idiosyncratic, or immunologic response.

•AE is an untoward medical occurrence in a patient who recivd an intervention/product, may or may not be causally related

•ADR is unintended and noxious response to a medication invariably leading to harm.

Medication errors:

•A medication error is an unintended failure in the drug treatment process that leads to, or has the potential to lead to, harm to the patient.

•A failure in the drug treatment process does not refer to lack of efficacy of the drug, rather it refers to human or process mediated failures.

•Medication error is a human or process mediated treatment failure and not due to medicine itself.

Medication errors include any and all of these steps:

• Prescribing (Drug prescription errors)

• Storing

• Dispensing

• Preparation for administration

• Administration of a medicinal product

• Potential medication error

Two types of medication errors:

• Active errors:

Errors occurring at the point of the interface between humans and a complex system

• Latent errors:

The hidden problems within healthcare systems that contribute to the event

Add alt text

Causes of medication errors:

Common causes of medication error include:

• Incorrect diagnosis
• Prescribing errors
• Dose miscalculations
• Poor drug distribution practices
• Drug and drug device related problems
• Incorrect drug administration
• Failed communication and lack of patient education

Medication errors in aggregate reports

Section 9.2 of PBRER covers medication errors.

Search strategy:

• MEddRA has an HLGT concerned with medication errors.
• However, many of the ADR reports with the HLGT term medication error are not medication errors in accordance with the definition (e.g. intentional poisoning, off-label use, interactions, quality issues, irrelevant exposure terms, information of incompatibility etc.)
• To alleviate this problem, MEDDRA has included SMQs (with broad and narrow scopes) dedicated to Medication error.
• However, medical reviewer oversight is necessary to identify and include only ‘true’ medication error cases in the PBRER section analysis.
• Some PTs/ concepts are notorious for being prone to being considered as medication errors when actually they are not.
• In particular, PTs related to overdose, need careful event-by event consideration for inclusion or exclusion in section 9.2 PBRER.
• In overdose related PTs found during reporting period, focus should be on intention behind overdose.
• By definition, medication errors have to be unintentional, hence anyPTs related to intentional overdose would by default be not considered as medication error.
• On the other hand, PTs such as accidental/unintentional overdose and analogous ones would be considered as medication errors.
• In PTs simply saying ‘overdose’, thorough review of the whole narrative, ideally by a medical reviewer should be done and decision should be made.
• One gray area would be PT overdose coded in a narrative with patient having a tendency of drug abuse.
• While theoretically, a patient with drug abuse is prone to accidental overdose due to adverse (massively if I may say so) impact of abused drugs on judgement capacity of an individual and positive reward generated by the human brain during such abuse (such as in ‘Barbiturate fog’ in which patient loses the insight of how many tablets already consumed and keeps on consuming more and more → resulting in unintentional/ accidental overdose and ergo, is a medication error), often co-existing depression and/or suicidality can also mean the overdose can be intentional in such patients.
• Hence, medical oversight can really make a difference in such medication error cases.

Presentation of medication errors section 9.2 in PBRER:

What regulators want to see in this section is:

• Root cause analysis of types of medication error
• How many medication error related cases had AEs
• How many medication errors actually caused AEs
• MAH comment delineating overall analysis, what is known, what is mentioned in the RSI or other reference document and how the MAH wants to prevent future medication errors.

There are multiple way and approaches to present this analysis which merits a separate article (coming soon!)

Some PTs which meet the definition of medication errors:

• Accidental overdose

• Drug administration error

• Drug dose omission

• Drug name confusion

• Expired drug administered

• Incorrect dose administered

• Incorrect route of drug administration

• Intercepted drug administration error

• Labelled drug-drug interaction medication error

• Medication error (the PT, obviously)

• Wrong drug administered

Classification of medication errors (IPAD):

I- Intercepted medication errors

P- Drug prescription errors

A- Drug administration errors

D- Drug dispensing errors

Let’s understand each of these types of medication errors in a bit detail:

1- Intercepted medication error (‘near miss’)

• In the context of pharmacovigilance, an intercepted error indicates that an intervention caused a break in the chain of events in the treatment process before reaching the patient which would have resulted in a ‘potential’ ADR.

• The intervention has prevented actual harm being caused to the patient, e.g. a wrongly prepared medicine was actually not administered to the patient because the error was noticed by the nurse.
• In the context of patient safety reporting systems, the term ‘near miss’ is used as synonym for describing what is classified ‘intercepted error’ for pharmacovigilance purposes.
• A near miss from a patient safety perspective is a random break in the chain of events leading up to a potential adverse event which has prevented injury, damage, illness or harm, but the potential for harm was nonetheless very near.

2- Drug prescription errors:

• Preventable errors occur because systems for safely prescribing, and ordering medication are not appropriately used.

• A widely recognized cause of error is illegible handwritten prescriptions.

• Errors may result from insufficient or missing information about co-prescribed medications, past dose-response relationships, laboratory values and allergic sensitivities.

• Errors in prescribing can occur when an incorrect drug or dose is selected, or when a regimen is too complex.

• When prescriptions are transmitted orally, sound-alike names may cause error.

• Similarly, drugs with similar-looking names can be incorrectly dispensed when prescriptions are handwritten.

• Errors may occur because a prescription is never transmitted to a pharmacy, or a prescription is never filled by the patient.

• Physician sampling of medications can contribute to medication errors due to the lack of both adequate documentation and drug utilization review.

Root causes of drug prescription errors:

•Bad handwriting (yours truly has been guilty of taking ‘doctor handwritings’ to the extreme.. In fact, my first employer sent a company-wide email with do’s and don’ts and item 5 showed my handwritings as an example how not to write!)

• Sound-alike if medication is prescribed orally

• Look alike medicines

• Complex drug regimes

• Insufficient/missing information regarding co-prescribed medications

• The lack of both adequate documentation and drug utilization review

• Prescription is never transmitted to a pharmacy, or a prescription is never filled by the patient

Drug dispensing errors:

• The term dispensing error refers to medication errors linked to the pharmacy or to whatever health care professional dispenses the medication.

Drug dispensing errors of commission:

• Something we did that led to med error (dispensing the wrong stuff)

• These include errors of commission (e.g. dispensing the wrong drug, wrong dose or an incorrect entry into the computer system)

Drug dispensing errors of omission:

• Something we did not do/missed to do which led to med error (missed vigilance)

• e.g. failure to counsel the patient, screen for interactions or ambiguous language on a label)

• Errors may be potential — detected and corrected prior to the administration of the medication to the patient.

• The three most common dispensing errors are:

1. Dispensing an incorrect medication, dosage strength or dosage form
2. Miscalculating a dose
3. Failing to identify drug interactions or contraindications

Drug administration errors:

• Errors caused by drug administration can be made by the health care provider or by the patient themselves.

• Much of the problem in drug administration is communication.

• Patients are often unaware that errors can happen and often do not take an active role in understanding what is being communicated to them.

• Errors most often occur when communication is unclear regarding drug name, drug appearance, why the patient is taking the drug, how much and how often to take it, when is the best time to take it, how long to take it, what common side effects could occur, what to do about a missed dose, common interactions with other drugs or foods, and whether this new drug replaces or augments other therapy.

• Over-the-counter medications can lead to medication errors because labels may not be sufficiently read or understood, and health care providers are often unaware when patients are taking over-the-counter medications.

Risk categorization of medication errors:

•Any risk minimization measures proposed by the MAH to reduce confusion between newly marketed and existing products (where significant changes to the marketing authorisation or line extensions have been introduced) should be discussed in the RMP.

The decision whether to classify the adverse outcome due to a medication error as an important risk will depend on:

1-The number of cases reported in clinical trials or in post marketing use

2- The level of risk associated with this error

When to make medication error as a potential risk?

• Situations where medication errors may occur but where the impact of medication errors occurring is uncertain may represent a potential risk

Examples:

• Risk of overdose resulting from inaccurate dosing of an oral liquid medication

• Risk of decreased efficacy resulting from difficulty using the administration device

• ME can occur but impact uncertain à Potential risk

When to consider medication error as an identified risk?

• Where reports of medication errors have been received which have resulted in adverse outcomes, medication error (specifying the adverse outcome) should be considered an identified risk

• So, cases identified due to medication error → Identified risk

When to consider medication error as an important safety concern?

•A medication error leading to a risk which impacts on the benefit-risk balance of the product or which has implications for public health may be considered an important safety concern and be included in the RMP.

• Both routine and additional risk minimization measures may be implemented to reduce the risk of medication errors.

MAH obligations for reporting medication errors:

MAHs have obligations:

• To describe and discuss patterns of medication errors and potential medication errors within every periodic safety update report (PSUR), even when these are not associated with adverse outcomes.

• Development safety update reports (DSURs) should also include any evidence of clinically significant medication errors.

Keys to Medication Error Prevention:

• Patient education

• Prior authorization

• Electronic prescription recrods

• Bar coding (NDC and expiry dates)

• EDURà Electronic Drug Utilization Record

• Automated Medication Dispensing

• Internal Quality Control Procedures

Medication error- risk management planning (RMPs):

Risk management planning in relation to medication errors should be:

• Proactive

• Beginning at an early stage in product development

• Focus should be more during drug development stage to prevent

• Continuing with the development of newly marketed products

• Medication errors can arise at any stage of the treatment process, including prescribing, storing, dispensing, preparation for administration or administration

• Such errors can lead to over- or underdosing, incorrect application via the wrong route of administration or administration to the wrong patients

• The consequences may include serious adverse reactions including death, an increased incidence and/or severity of adverse reactions and loss of effectiveness.

• During the product development process, applicants should consider the various sources of medication error, their relevance for the product and the likely impact on the balance of risks and benefits.

The context of reports of medication errors in aggregate reports and RMP:

The context of product use should be considered and discussed in relation to these reports, including:

• The setting of use

• Stage of medication process

• Category (type) of medication error

• Contributing factors

• Medicinal products involved

• Variables amongst the treated population

• Patient outcome

• Seriousness

• Region/country of occurrence

• Mitigating factors

Last but not the least, a very common interview question that requires understanding:

The difference between potential medication error and intercepted medication error?

Let’s take a look at the most famous picture of medication errors below:

Add alt text

To understand classification of med errors, we have to focus on where the break in sequence happened and what was the end result for the patient?

What is a potential medication error?

The term potential medication error refers to all possible mistakes in the prescribing, storing, dispensing, preparation for administration or administration of a medicinal product by all persons who are involved in the medication process and may lead to:

• A medication error with harm, but without knowing the actual cause,

• A medication error without harm and without knowing the actual cause

• A medication error without harm, but with the awareness of the actual cause.

• Potential medication error means all medication errors except the ones leading to harm with known cause.
• In other words, a potential medication error is recognition of circumstances that could lead to a medication error, and may or may not involve a patient

Intercepted medication error (‘near miss’):

• In the context of pharmacovigilance, an intercepted error indicates that an intervention caused a break in the chain of events in the treatment process before reaching the patient which would have resulted in a ‘potential’ ADR.

• The intervention has prevented actual harm being caused to the patient but actual error has already occurred (as opposed to potential medication error where break occurs before actual error), e.g. a wrongly prepared medicine was actually not administered to the patient because the error was noticed by the nurse.
• In the context of patient safety reporting systems, the term ‘near miss’ is used as synonym for describing what is classified ‘intercepted error’ for pharmacovigilance purposes.
• A near miss from a patient safety perspective is a random break in the chain of events leading up to a potential adverse event which has prevented injury, damage, illness or harm, but the potential for harm was nonetheless very near.

The actual difference between potential medication error and intercepted medication error:

• A clear distinction should be made between medication errors associated with adverse reaction(s), medication errors without harm, intercepted medication errors and potential medication errors depending on where the break occurs in the chain of events leading to the error and its consequences for the patient

• If a medication error occurred but was recognized and intercepted before reaching to the patient means resulting in no harm to the patient is intercepted medication error.

Types of med errors:

• Chain of events → Error → Reaches the patient → Harm= ME with harm

• Chain of events → Error occurs → Reaches the patient → Does not result in a harm → ME with no harm

• Chain of events → à Error occurred → Did not reach the patient → NO harm to the patient → Intercepted medication error

• Chain of events → Error did not occur → Potential medication error

Take home way of telling difference between potential medication error and intercepted medication error:

1. So, in short, break occurs before error → Potential error (could have been an error but never occured in reality- recognition of circumstances),
2. Break occurs after an error has occurred but before reaches the patient → intercepted medication error (actual error occurred but due to an intervention, could not harm the patient)

•I would conclude this article here. Hope you enjoyed reading, please tell or discuss your thoughts in comments below :)