Milena Miljkovic ([email protected]). For such chemotherapy-related, common adverse effects (anticipated adverse events) there is no need to perform causality assessment using any of the existing causality assessment algorhitms/scales, because you have allready assessed them using your clinical judgment that such event(s) are related to chemotherapy. However, the assessmet of event severity (for each of the events) should be performed per CTCAE Ver. 5.0 (mild/Grade 1; moderate/Grade 2; severe/Grade 3; life-threatening/Grade 4; and death/Grade 5), as well as the assessment of event seriousness per ICH-E2A (seriousness criteria are specified also on the CIOMS-form, including: death; new/prolonged hospitalization; persistant/significant dissability/incapacity; life-threatenng; congenital anomaly; and other medically important event).

There is a difference between adverse effect, side effect, and adverse event.

Adverse effect is undesirable effect that occurs as a response to a drug, which is noxious and unintended.

Side effect is unintended/unwanted effects, usually secondary effect that occur due to a drug, in addition to its intended effects.

Adverse event is any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related.

You should do causality-assessment if you want to eliminate confounding factors.

Milena Miljkovic (miljkovic.milena57@yahoo)

An underlying malignancy, other comorbidities and concomitant medications may contribute to the development of chemotherapy-related, common adverse effects, but whether they can confound causal relationship between used chemotherapy and manifested chemotherapy-related, common adverse effects is assessed also by medical judgment (even in the presence of confounders, causality is still at least „possible“ for chemotherapy-related, common adverse effects).

An allergy is an adverse drug reaction mediated by an immune response (e.g., rash, hives). A side effect is an expected and known effect of a drug that is not the intended therapeutic outcome. Hope it is clear.

Thanks Milena M Miljkovic for your valuable response.

Here I want to add one more difference between side effect and adverse effect, in the perception of Clinical Trials.

If you find any undesirable/unwanted effects during phase trials(till phase III) are called Side effects. And finding any undesirable/unwanted effects during post marketing surveillance (phase IV) are called Adverse effects.

In detail, Suppose if you enter into a clinical trial with a new chemical entity which showing a desire pharmacological effect. here till phase III trials it shows it's desire pharmacological effect along with few undesirable/unwanted pharmacological effects which we are calling as Side effects.

After phase III trials and FDA approval, this drug with the leaflet mentioned with those possible side effects enters into the market. Here during post marketing surveillance (Phase IV) this same drug has to expose to various climate/storage conditions, has to expose to different individuals with different cultures, food habits, and health conditions(co-morbidity). In these circumstances this drug may show few more undesirable/unwanted effects, that we are calling as Adverse Effects.

Am I right?

thank you very much Mohd Masnoon Saiyed for your answer.

thanks Nitin Kulkarni for your comments

Milena Miljkovic: Since in clinical trials of a new chemical entity, we do not know much about effects of an investigational product, because they are being investigated (in controlled conditions and in a limited number of subjects/patients), therefore the term “side effect” is more appropriate. During the first five years of post-marketing monitoring, that drug is administered to a wider population (in patients with other comorbidities, who use other drugs) and, therefore, the term “adverse effect” is more appropriate. However, in order to avoid any confusion in terminology, the use of the following two terms in pharmacovigilance/drug safety is recommended: “adverse event” and “adverse reaction”. Definitions for these two terms are internationally accepted (Guideline ICH E2A, EMA-GVP Annex I, etc.) and the differences between them are clear, regardless whether we use them in clinical trials or post-marketing settings. Finally, in the product information (USPI, SmPC), the term “adverse reaction” is used (the term "undesirable effects" is used only for the title of section 4.8 of SmPC, within which "adverse reactions" are included).

Thanks Milena M Miljkovic for your valuable information.