This detailed blog focuses specifically on adverse events, covering:
- Understanding Lack of Efficacy and What It Isn’t
- Assessing Cases to Determine Lack of Efficacy
- Exploring Why Lack of Efficacy is Special Cases in Pharmacovigilance
Table of Contents:
- Differences in Definitions Between Efficacy and Lack of Efficacy
- Factors Undermining the Assessment of Lack of Efficacy Scenarios in Pharmacovigilance
- The Role of Pharmacovigilance in Elevating Efficacy Through LOE
- MedDRA Criteria for Coding Lack of Efficacy
- Addressing LOE to FDA
- Key takeaways
- Conclusion
- References
Definitions
Before we delve into the details of Lack of Efficacy (LOE), let’s first understand what efficacy means so we can grasp the concept of LOE more clearly.
Efficacy
In pharmacology, efficacy refers to how well a drug works and the maximum effect or the response it can produce. There are two main aspects to consider:
- Method effectiveness: This refers to the highest response achieved when using the drug as prescribed.
- Use effectiveness: It’s about how the drug performs in real-world situations compared to its expected effects based on clinical studies and research findings.
“The journey towards drug efficacy is paved with the vigilant pursuit of understanding, where each reported lack of efficacy becomes a beacon guiding us towards safer and more effective treatments.”
Lack of efficacy
Lack of efficacy is defined as:
- Specifically, the administered drug did not work or was inefficient in producing the expected effect under the conditions of recommended use.
- If the administered drug did not alter the nature of a particular disease for the better.
- Not benefiting, not being utilized by the individual, or not preventing or controlling the existing condition.
- Did not achieve the desired result/ improvement, even when the drug was taken under ideal circumstances.
- The probability of expected benefit not being received correctly.
Difficulty in Determining Lack of Efficacy
There is no shortage of definitions for Lack of efficacy; nor is there relating to distinctions between terms such as efficacy, effectiveness and Lack of efficacy.
Many people have misconceptions about what lack of efficacy truly entails. Below are a few examples to clarify:
Examples Excluded from Lack of Efficacy Assessment
Few examples of situations that might appear similar to Lack of Efficacy (LOE) but are not:
- Feels ineffective but Usage of the drug for a condition it’s not intended for.
- Choosing or administering the wrong drug or dosage.
- Using counterfeit or fake medication.
- Errors in medication administration.
- Using a drug obtained from an unauthorized source.
- It’s important to note that situations involving counterfeit products do not constitute Lack of Efficacy.
Examples Included to Lack of Efficacy Assessment
Below are a few examples, both known and unknown, of verbatims that actually indicate Lack of Efficacy (LOE):
- Failure of therapeutics effects
- Failure of drug treatment
- Confirmed clinical vaccine failure
- Remission not achieved
- Low drug level
- Therapy non-responder
- Drug level abnormal
- No drug effect
- Drug effect variable
- Wearing off effect
- Drug resistance
How Pharmacovigilance Elevates Efficacy through LOE?
Through pharmacovigilance processing, we can explore various aspects related to Lack of Efficacy (LOE) cases, including:
- Identifying counterfeit and fake drugs.
- Discovering unauthorized dealers.
- Initiating the recall of specific batches of drugs.
- Conducting cross-verification and pre-marketing studies to assess current effects post-market.
- Comparing the effects of the latest superior marketed drug with existing drugs in the market.
When patients, healthcare professionals, or others notice or suspect that a medication isn’t working as expected, it’s important to report this to regulatory authorities or the drug manufacturer.
These reports help evaluate the safety and effectiveness of the medication over time.
📢 Check out, To learn more in detail about the role of Drug Regulatory Authorities.
Investigating and addressing lack of efficacy is crucial for patient safety. It could lead to further studies, updates to labels, changes in dosing, or even removing the medication from the market if needed.
Continuously monitoring and reporting lack of efficacy helps maintain the safety and quality of medications.
If a report mentions lack of efficacy along with suspected counterfeit medication use, it should initially only be coded as a counterfeit case. The lack of efficacy should be disregarded until confirmation and investigation confirm that the drug is not fake or counterfeit.
MedDRA Criteria for Coding Lack of Efficacy
Table 1
Criteria used to classify reports as “useful” for manual evaluation
| Criterion | Description |
|---|---|
| 1 | The suspect product of drug ineffective was clearly identifiable |
| 2 | An informative narrative to support the reported drug ineffectiveness AND one or more of the following four criteria: |
| 3 | MedDRA preferred term(s) in addition to “drug ineffective” was reported |
| 4 | Suspect product’s batch or lot number was reported |
| 5 | A beneficial response prior to the administration of the suspect product was reported |
| 6 | Medication switching was reported |
Addressing LOE to FDA
- File a Form FDA 1639 and submit for all spontaneous domestic reports of “lack of effect” in the periodic report with other ADE’s.
- The inclusion of lot number of the suspect drug is mandatory in Item 14.
- Regular analysis for at least quarterly during the initial 3 years post-marketing, and annually thereafter, to monitor any potential increase in frequency.
- Detection of increase in frequency, and the same submission of narrative report within 15 days of detection.
- Analyze the spontaneous reports separately and however, the LOE reports from foreign reports not necessary.
- If the report of “lack of effect” is for an unapproved indication, the event is not reportable. However, the inclusion of this information is compulsory in the narrative summary section of the- periodic report.
Key take away:
- The collection of reports from lack of therapeutic efficacy is mandatory and if even they do not meet the minimum requirements, so further follow-up attempt(s) must be performed.
- The cases that the aggravation or the progression of the disease not attributed to the drug ineffective.
- The reports are not associated with suspected adverse drug reactions not LOE.
- Record of lack of therapeutic efficacy with the most appropriate MedDRA terms should be used to describe the clinical condition of the patient.
- If the report of “lack of effect” is for an unapproved indication, the event is not reportable.
Wrap-up
Hope the above write-up proves helpful in assessing the scenarios we’ve discussed. It aims to clear up any confusion and provide valuable insights for beginners facing interviews or Q&A sessions.
If there are any specific areas I may have missed discussing or if you wish to explore further topics within this subject, feel free to let us know.
Your feedback on this article is greatly appreciated, and if there are any recommendations or corrections you’d like to suggest, I’m all ears. Thank you for your attention thus far.
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