What is the compensation formula for injury or death in clinical trials in India under the New Drugs and Clinical Trials Rules, 2019?

Compensation for Clinical Trial-Related Injury or Death in India

Overview of the New Drugs and Clinical Trials Rules, 2019

The New Drugs and Clinical Trials Rules, 2019 establish a structured compensation framework for participants who suffer injury or death during clinical trials in India, with formulas based on age, risk factors, and type of injury. 1

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When Compensation is Applicable

Compensation must be provided by the sponsor in the following circumstances:

• Serious Adverse Events (SAEs) occurring during clinical trials, bioavailability studies, or bioequivalence studies that are causally related to the trial 1
• Injury or death resulting from adverse reactions to the investigational product 1
• Harm due to protocol violations or negligence by the sponsor or investigator 1
• Injury from placebo use in placebo-controlled trials 1
• Injury from concomitant non-standard medications required by the trial 1
• Injury to a fetus resulting from a parent's trial participation 1
• Harm from trial-related procedures 1

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Compensation Formula for Death

For clinical trial-related death, compensation is calculated as:

Compensation = (B × F × R) / 99.37 1

Where:

• B = ₹8,00,000 (base amount) 1
• F = Age factor from the Workmen's Compensation Act (Annexure 1) 1
• R = Risk factor ranging from 0.5 to 4.0 based on disease severity 1

Risk Factor Scale:

• 0.5 = Terminally ill patients (expected survival ≤6 months) 1
• 1.0 = High-risk patients (expected survival 6-24 months) 1
• 2.0 = Moderate-risk patients 1
• 3.0 = Mild-risk patients 1
• 4.0 = Healthy volunteers or no-risk subjects 1

Special provision: For patients with ≥90% expected 30-day mortality, a fixed amount of ₹2 lakhs is paid 1

Compensation range: Minimum ₹8 lakh to Maximum ₹73.6 lakh depending on age and risk factors 1

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Compensation Formula for Permanent Disability

For permanent disability resulting from clinical trial participation:

Compensation = (C × D × 90) / (100 × 100) 1

Where:

• C = Compensation amount that would have been paid if death had occurred 1
• D = Percentage of disability suffered by the trial subject 1

Key principle: 100% disability equals 90% of the death compensation amount; lesser disabilities are proportionate to the actual percentage 1

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Compensation for Congenital Anomaly or Birth Defect

When congenital anomaly or birth defect occurs due to either or both parents' participation in a clinical trial:

Lump-sum compensation = ₹4 lakh (half of the base amount) 1

This applies to:

• Stillbirth 1
• Early death due to anomaly 1
• Correctable deformity 1
• Permanent mental or physical disability 1

Additional provision: For correctable deformities or permanent disabilities, the sponsor must provide long-term medical management over and above the financial compensation 1

The lump sum is calculated to generate monthly interest approximately equal to half the minimum wage of an unskilled worker in Delhi 1

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Compensation for Reversible SAE or Life-Threatening Disease

For hospitalization due to clinical trial-related reversible SAE or life-threatening disease:

Compensation = 2 × W × N 1

Where:

• W = Minimum daily wage of an unskilled worker in Delhi 1
• N = Number of days of hospitalization 1

Rationale: The doubling factor accounts for wage loss, attendant costs, indirect expenses, and inconvenience 1

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Reporting and Assessment Process

Timeline for SAE Reporting:

1. Within 24 hours: Investigator must report all SAEs to the Central Licensing Authority (CLA), sponsor, and Ethics Committee (EC) 1

   • Failure to report requires documented reasons for delay 1

2. Within 14 days: For SAE of death, sponsor and investigator submit analyzed reports to CLA and head of institution 1

3. Within 30 days: EC forwards its report on SAE of death with compensation opinion to CLA 1

4. Within 60 days: Independent Expert Committee (constituted by CLA) examines the case and recommends cause of death and compensation quantum 1

5. Within 30 days of final order: Sponsor must pay the compensation 1

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Role of the Ethics Committee

The EC has critical responsibilities in the compensation process:

• Safeguards participant rights, safety, and well-being throughout the trial 1
• Reviews and recommends SAE compensation within 21 days of receiving the report 1
• Approves protocols and ensures ethical compliance before trial initiation 1
• Forwards compensation recommendations to CLA with detailed analysis 1

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Limitations and Exclusions

Compensation is NOT provided in the following circumstances:

• Lack of therapeutic benefit from the investigational drug 1
• Injury from a comparator drug or licensed product 1
• Injury where subject negligence or protocol deviation by the subject occurred 1

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Key Implementation Challenges

Several practical concerns have emerged since the 2019 rules were enacted:

• Ensuring sponsor compliance with compensation payment obligations within mandated timelines 2, 3
• Transparency with participants regarding their compensation rights before enrollment 2
• Timely SAE reporting to enable prompt resolution and payment 2
• Economic erosion: The compensation formulas finalized in 2013 and carried forward to 2019 may not reflect current economic realities, potentially undervaluing participant protection 3
• Training gaps: The rules do not clearly define training requirements for EC members and other stakeholders involved in compensation assessment 3
• Interpretation challenges: Some aspects of Rule 122 DAB (incorporated unchanged from earlier regulations) remain problematic and need revision for smooth implementation 3

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Medical Management Responsibility

Beyond financial compensation, sponsors must provide:

• Free medical management for all trial-related injuries requiring treatment 1
• Long-term medical care for birth defects and permanent disabilities, over and above financial compensation 1
• Immediate intervention for any SAE, regardless of final causality determination 1