What is Efficacy?

By Marzia KhanReviewed by Danielle Ellis, B.Sc.

Efficacy in healthcare interventions
Efficacy in pharmacology
Efficacy in clinical trials
Efficacy vs. effectiveness
Challenges and limitations in measuring efficacy
Real-world applications
References
Further reading

Efficacy can be defined as the capacity to generate an effect, such as lowering blood pressure. This is measured under ideal conditions with expert supervision in a group of patients through a controlled clinical trial, which is the basis for the healthcare and pharmacology industry.¹

Interestingly, efficacy is not the same as effectiveness, with effectiveness being defined as how well a drug works when used in the real world. This is significant as a drug may show results of having high efficacy in lowering blood pressure within clinical trials. However, it may be low in effectiveness due to several adverse effects, leading to patient disuse.¹ A treatment is considered to be “effective” if it works in real life in non-ideal conditions.²

Efficacy in healthcare interventions

Observational studies and randomized controlled trials are predominantly used to evaluate the efficacy of treatments. Real practice studies can also be used to assess interactions with other medications as well as interactions with health conditions in patients.²

Pharmaceutical interventions are used to address many health conditions and diseases that cannot be managed through surgery or when surgery is not preferred by the patient. Studying the efficacy of various interventions optimizes shared decision-making for both patients and physicians.³

Randomized controlled trials (RCTs) are the gold standard for modern evidence-based medicine and are used to investigate evidence of efficacy and safety of new drugs. They are also the preferred method for assessing novel, high-risk medical devices when possible.⁴

However, medical devices can have their own route to market, such as through the Medical Device Regulation (MDR) framework that was implemented in the European Union (EU) in 2021, providing guidance on balancing efficient approval and showing evidence of safety.⁴

Analysis of drug efficacies is common; for example, a meta-analysis compared the efficacy and safety of COVID-19 vaccine RCTs, ranking four different categories of these vaccines according to risk ratio. The authors ranked the categories as followed: (i) inactivated vaccines; (ii) viral vector vaccines; (iii) protein subunit vaccines, (iv) mRNA vaccines.⁵

Inactivated vaccines were analyzed in this meta-analysis as having performed better than the others, based on the indirect comparison, with mRNA vaccines being at the bottom. Inactivated vaccines were also found to have the lowest risk of both local and systemic adverse events after being immunized. These analyses align with the knowledge that inactivated vaccines have a high level of safety due to the lack of viral genetic material.⁵

Efficacy in pharmacology

Principles of pharmacokinetics and pharmacodynamics are integral in drug development, enabling researchers to understand the efficacy of a drug.⁶

Maximum response (Emax) and the concentration of producing 50% of Emax (C₅₀) are two significant parameters of pharmacodynamics.⁶ Pharmacodynamics, which can sometimes be described as what the drug does to the body, includes analysis of physiologic, biochemical and molecular effects of the drug. It can also explain the relationship between the dose of the drug and its response.⁷

Dose-response data is usually visualized in a graph form, with the dose or dose function being on the x-axis and the measured effect, or response, being on the y-axis. The response is often recorded as maximal at the time of peak effect. A hypothetical dose-response curve can be seen in Figure 1, with varying features including (i) the potency (the location of the curve along the dose axis), (ii) the maximum efficacy (the maximum response attainable), (iii) and the slope (the change in response per unit dose).⁷

Graphing dose-response curves of drugs under the same conditions can assist in comparing the pharmacologic profiles of drugs, as well as aid researchers in determining the optimal dose for a desired response.⁷

Efficacy in clinical trials

As previously mentioned, randomized controlled trials are used to measure the effectiveness of interventions.^8,9 In these studies, participants are randomly assigned to either receive the drug (experimental group) or a comparator, which may either be a placebo or a standard of treatment.⁸ Randomization reduces bias and enables “cause and effect” relationships to be assessed between the drug and its outcome.⁹

In the United States, drug treatments are regulated through the Food and Drug Administration (FDA), with pharmaceutical companies requiring FDA approval before their drug is allowed onto the market for patient use. This approval is dependent on rigorous clinical trials on the efficacy and safety of drugs in patient populations.¹⁰

The European Medicines Agency (EMA) also provides regulatory approval for drugs that have demonstrated high efficacy and safety within clinical trials in Europe.¹¹

Efficacy vs. effectiveness

Efficacy and effectiveness studies hold significant roles in pharmaceutical research; however, they have distinctive purposes with varying study designs.

Efficacy studies aim to investigate the benefits and drawbacks of therapeutic interventions under highly controlled conditions; this includes placebo-controlled RCTs, which utilize restricted patient samples and have methodologic advantages and high internal validity.¹²

On the other hand, effectiveness studies, which are also known as pragmatic studies, aim to assess therapeutic interventions under conditions that are more closely related to real-world practice, including heterogeneous patient populations, as well as having less standardization in treatment protocols and delivery in routine clinical environments.¹²

Effectiveness studies may also utilize RCT designs but may use standard-of-care treatments as a comparator rather than a placebo. Fewer restrictions are placed in this study, which can reduce its internal validity but provide higher external validity.¹²

This distinction is significant for both patients and healthcare providers, ensuring full comprehension of the effects of the drug. Efficacy research increases the chance of seeing if there is an effect of the drug, while effectiveness trials account for external factors that may moderate the effect of a drug, such as patients, healthcare providers, and other system-level factors.¹²

Challenges and limitations in measuring efficacy

A challenge for efficacy studies includes its overestimation of an intervention’s effect when it is applied in clinical practice.¹²

For an intervention to be useful for patients, it must be (i) readily available, (ii) have a target population identified by providers, and (iii) have high adherence by patients. These parameters are significant as obstacles such as poor access and adherence rates can lead to highly efficacious interventions that are not as effective in practice.¹²

Additionally, efficacy trials that utilize placebo RCTs reduce trial biases and population differences, with standardization of interventions and double-blinding. This type of trial also eliminates access and adherence issues, with the intervention being provided for free and utilizing only participants who will accept and adhere to the trial.¹²

These standardizations and strict study design protocols do not reflect the real world with substantial deviations from clinical practice.¹²

Real-world applications

Efficacy data can aid healthcare decisions due to its capacity to drive beneficial or therapeutic change as a result of drugs being studied and made available to the public.²

With clinical trials being integral for the delivery of the next generation of therapeutics, pharmaceutical companies, including AstraZeneca, have aimed to increase the use of digital health tools for novel digital healthcare solutions in clinical trials.¹³

Digital health solutions carry the potential to decrease the burden of participation for both patients and trial teams. The design of trials with digital health tools aims to support health equity and inclusion, as well as increase delivery outcomes in a more environmentally sustainable approach.¹³

Bespoke tools such as Merlin can be used to provide an automatic score that is used to estimate the likely patient experience index for the study, which is based on the study design and patient feedback about the burden of visits and procedures. This can be used to compare new study designs with previous similar studies to improve patient experience, as well as provide data on cost, timeline, and environmental impact.¹³

References

1. Lynch SS. Drug Efficacy and Safety - Clinical Pharmacology. MSD Manual Professional Edition. https://www.msdmanuals.com/professional/clinical-pharmacology/concepts-in-pharmacotherapy/drug-efficacy-and-safety. Published May 2022. Accessed January 31, 2025.
2. Enrique B, Marta B. Efficacy, Effectiveness and Efficiency in the Health Care: The Need for an Agreement to Clarify its Meaning. International Archives of Public Health and Community Medicine. 2020;4(1). doi:10.23937/2643-4512/1710035. https://clinmedjournals.org/articles/iaphcm/international-archives-of-public-health-and-community-medicine-iaphcm-4-035.php
3. Zavalis EA, Rameau A, Saraswathula A, Vist J, Schuit E, Ioannidis JP. Availability of Evidence and Comparative Effectiveness for Surgical Versus Drug Interventions: An Overview of Systematic Reviews and Meta-Analyses. BMJ Open. 2024;14(1). doi:10.1136/bmjopen-2023-076675. https://pubmed.ncbi.nlm.nih.gov/38195174/
4. Buccheri S, James S, Mafham M, et al. Large Simple Randomized Controlled Trials—From Drugs to Medical Devices: Lessons From Recent Experience. Trials. 2025;26(1). doi:10.1186/s13063-025-08724-x. https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-025-08724-x
5. Wu X, Xu K, Zhan P, et al. Comparative Efficacy and Safety of COVID-19 Vaccines in Phase III Trials: A Network Meta-Analysis. BMC Infectious Diseases. 2024;24(1). doi:10.1186/s12879-023-08754-3. https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-023-08754-3
6. Holford N. Pharmacodynamic principles and the time course of immediate drug effects. Translational and Clinical Pharmacology. 2017;25(4):157. doi:10.12793/tcp.2017.25.4.157. https://pubmed.ncbi.nlm.nih.gov/32095468/
7. Farinde A. Dose-Response Relationships - Clinical Pharmacology. MSD Manual Professional Edition. https://www.msdmanuals.com/professional/clinical-pharmacology/pharmacodynamics/dose-response-relationships. Published November 2023. [Updated June 2024] Accessed January 31, 2025.
8. Braga LH, Farrokhyar F, Dönmez Mİ, et al. Randomized Controlled Trials – The What, When, How and Why. Journal of Pediatric Urology. December 2024. doi:10.1016/j.jpurol.2024.11.021. https://pubmed.ncbi.nlm.nih.gov/39701869/
9. Hariton E, Locascio JJ. Randomised Controlled Trials – The Gold Standard for Effectiveness Research. BJOG: An International Journal of Obstetrics & Gynaecology. 2018;125(13):1716-1716. doi:10.1111/1471-0528.15199. https://pmc.ncbi.nlm.nih.gov/articles/PMC6235704/
10. Types and Phases of Clinical Trials: What Are Clinical Trial Phases? What Are Clinical Trial Phases? | American Cancer Society. https://www.cancer.org/cancer/managing-cancer/making-treatment-decisions/clinical-trials/what-you-need-to-know/phases-of-clinical-trials.html. Published August 18, 2020. Accessed January 31, 2025.
11. Authorisation of Medicines. European Medicines Agency (EMA). https://www.ema.europa.eu/en/about-us/what-we-do/authorisation-medicines. Accessed January 31, 2025.
12. Singal AG, Higgins PD, Waljee AK. A Primer on Effectiveness and Efficacy Trials. Clinical and Translational Gastroenterology. 2014;5(1). doi:10.1038/ctg.2013.13. https://pmc.ncbi.nlm.nih.gov/articles/PMC3912314/
13. Duran C, Bonam M. Clinical Innovation: How Digital Health Solutions are Transforming Our Trials. https://www.astrazeneca.com/what-science-can-do/topics/clinical-innovation/clinical-innovation-digital-health-solutions-transforming-trials.html. Published September 26, 2023. [Updated November 2023] Accessed January 31, 2025.

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