Related Experiment Video
Updated: Aug 13, 2026
09:38
Determining Pain Detection and Tolerance Thresholds Using an Integrated, Multi-Modal Pain Task Battery
Published on: April 14, 2016
Model-Informed Drug Development (MIDD) for Analgesics: Review of Applications, Regulatory Integration, and Emerging
Albert Dahan1,2, Joseph V Pergolizzi2, Marieke Niesters3,4
1Clinical Sciences, MediD Consultancy Group, Amsterdam, the Netherlands.
Journal of Pain Research
|August 12, 2026
Summary
Model-Informed Drug Development (MIDD) offers quantitative tools to address challenges in analgesic drug development, such as high placebo rates and opioid safety. While MIDD is increasingly used, its full potential for analgesic development remains to be realized.
Area of Science:
- Pharmacology
- Drug Development
- Quantitative Systems Pharmacology
Background:
- Analgesic drug development faces unique hurdles including high placebo response rates, subjective pain assessment variability, opioid safety concerns, and dose optimization difficulties.
- Model-Informed Drug Development (MIDD) encompasses various quantitative modeling and simulation methods relevant to these challenges.
Purpose of the Study:
- To review MIDD methodologies and their application across all phases of drug development, focusing on analgesic development.
- To clarify the progress and remaining gaps in applying MIDD to analgesic drug development.
Main Methods:
- Narrative review of literature identified through PubMed, EMBASE, and regulatory agency databases.
- Analysis of modeling and simulation contributions to regulatory decisions and drug approvals.
- Examination of regulatory frameworks and initiatives supporting MIDD.
Main Results:
- Modeling and simulation analyses informed over 60% of novel drug approvals by the FDA (2010-2020).
- Clinical trial simulation improves Phase II-to-Phase III transition rates and statistical power.
- Physiologically Based Pharmacokinetic (PBPK) modeling supports pediatric dose selection, with predictions generally within twofold of observed values.
- Regulatory adoption of MIDD has reduced uncertainty and incentivized investment.
- MIDD tools have been applied to opioid safety, dose development for specific analgesics, and bioequivalence studies, but no analgesic has undergone fully MIDD-centric development.
Conclusions:
- MIDD represents a significant shift towards evidence-driven, model-guided drug development.
- MIDD has substantial, though not yet fully realized, potential to overcome specific challenges in analgesic drug development.
- Further integration and application of MIDD are needed to optimize analgesic development processes.
Related Concept Videos
01:25Analgesia and Pain Management
Pain is critical to various clinical pathologies, provoking an urgent need for effective management. Pain, whether acute or chronic, is a complex neurochemical process. Its alleviation depends on the type, with nonopioid analgesics effective for mild to moderate pain, such as musculoskeletal or inflammatory pain, while neuropathic pain responds best to anticonvulsants, tricyclic antidepressants, or serotonin/norepinephrine reuptake inhibitors. For severe acute or chronic pain, opioids may be...
01:25Drug Regulation
Drug regulation encompasses the management of drug usage by evaluating its safety and efficacy through assessments conducted by regulatory authorities. Regrettably, the history of drug regulation is marred by several catastrophic events. One such incident is the Elixir Sulfanilamide tragedy, in which the toxic compound diethyl glycol was included in a sweet-tasting medication, leading to numerous fatalities. This event prompted the enactment of the Food, Drug, and Cosmetic Act in 1938. Under...
01:15Impact of Pharmacokinetic–Pharmacodynamic Models: Regulatory Decisions
PK–PD modeling has significantly influenced FDA regulatory decisions, particularly drug approval, dosage optimization, and labeling. These models integrate pharmacokinetics (PK) and pharmacodynamics (PD) to predict drug behavior and effects, aiding in optimizing dosing regimens and enhancing the probability of clinical trial success.One notable example is Nesiritide (Natrecor®), a recombinant human brain natriuretic peptide for treating acute decompensated congestive heart failure (CHF).
01:28Structure-Activity Relationships and Drug Design
Drug design is a dynamic field that involves discovering and developing new medications based on specific biological targets. This process heavily relies on structure-activity relationships (SAR) and quantitative structure-activity relationships (QSAR) to guide the design and optimization of efficient drugs.
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence its...
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence its...
01:26Drug Discovery: Overview
Drug discovery is a multifaceted process involving extensive screening, testing, and optimization of lead compounds to identify potential new drugs for therapeutic use. It combines several approaches, including screening large numbers of natural products, chemical modification of known active molecules, identification of new drug targets, and rational design based on biological mechanisms and drug-receptor structure. These approaches are carried out in both academic research laboratories and...
01:15Opioid Analgesics: Synthetic and Semisynthetic Opioids
Synthetic and semisynthetic opioids are pivotal in pain management and tackling opioid addiction. Semisynthetic opioids, including morphinans (morphine derivatives), oxycodone, oxymorphone, hydrocodone, and hydromorphone, have improved pharmacokinetic profiles compared to morphine. Additionally, heroin and 6-MAM (6-Monoacetylmorphine) show better CNS penetration than morphine due to heightened lipid solubility. Hydromorphone, a potent opioid, undergoes hepatic metabolism to form the active...