It's possible – but not always appropriate.
Can you skip MAD studies?
See how it works
Discover if an alternative pathway fits your program with our Early Phase Decision Guide. In about 10 minutes, you'll evaluate if your program is a good candidate, identify key risks early and prepare for regulatory discussions.
Developed from our experience.
Here's how it works
The Early Phase Decision Guide walks you through six critical factors to understand your readiness, identify gaps, and get results based on your inputs to discuss with experts. It's not a replacement for expert consultation. Every program is unique, and our experts can dive deeper into your specific situation.
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Regulatory engagement
What is your regulatory engagement status?
A
Why it matters Early regulatory engagement is critical. Alternative pathways are not standard - you need to build alignment with regulators before proceeding. Pre-IND meetings or scientific advice sessions let you gauge regulatory appetite, address concerns early, and avoid costly surprises like clinical holds.
Received positive feedback from regulators supporting an alternative pathway
B
No regulatory engagement yet
C
Regulators expressed concerns or requested traditional pathway
D
Go to next factor
Planning or scheduled pre-IND/scientific advice meeting
Significant gap. Proceeding without regulatory input is risky. Schedule a pre-IND meeting before committing to an alternative pathway. Our regulatory experts can help.
Critical issue. If regulators have already expressed concerns, alternatives are likely not viable.
Good proactive approach. Complete this engagement before finalizing your strategy.
Huge advantage. Regulatory support is one of the strongest predictors of success.
Scientific rationale
What is your primary scientific rationale for considering an alternative pathway?
Why it matters This is the most critical scientific factor. The strongest case for alternative pathways is when the drug can ONLY be evaluated in patients with the disease, or when there are compelling safety or PK/PD reasons to go directly to patients.
Drug mechanism/target only assessable in patients with disease (disease-specific biomarkers, patient-specific effects)
Drug too toxic for healthy volunteer MAD studies (safety justification)
Well-established drug class with strong modeling/simulation supporting dose selection
Disease significantly affects PK/PD, requiring patient data for dose selection
Valid safety rationale. If the drug is too toxic for HV, patient studies may actually be safer with appropriate monitoring.
Moderate rationale. Known classes benefit from historical data and predictive modeling.
Strongest rationale. If your drug's effects can only be assessed in patients with the disease, this is a key scientific justification.
Strong rationale. Disease-affected pharmacokinetics/dynamics require patient data to establish safe doses.
Disease characteristics
Which best describes your target disease?
Why it matters Regulators are more flexible when there is high unmet medical need, especially in rare or life-threatening diseases. The severity and rarity of the disease strengthens the case for expedited development.
Life-threatening or severely debilitating rare disease with high unmet need
Chronic or mild condition, or well-served by existing therapies
Serious disease with moderate unmet need
Harder to justify. Consider whether the time savings outweigh the risks.
Strongest candidate. Rare, life-threatening diseases with high unmet need are the most favorable for alternative pathways.
Acceptable but requires strong justification. Serious diseases can support alternative pathways if other factors align.
Patient population
Can your patient population tolerate slow, conservative dose escalation?
Why it matters Alternative pathways require slow, conservative dose escalation in patients. This takes time. If your patient population cannot tolerate this, you may actually save time by doing MAD studies in HV first.
Yes - disease progression is slow, and we have sufficient patients available
No - patients need rapid dose optimization OR very limited patient pool
Uncertain - need more analysis
Possibly - tight but manageable with careful planning
Consider whether HV studies might actually be faster. If patients need rapid optimization, MAD studies in HV can identify the right dose quicker.
Critical to analyze before deciding. Model out timelines for both approaches.
Favorable conditions. Slow disease progression and adequate patient availability support the extended timelines needed for conservative escalation.
Requires careful planning. Work with experts to design an escalation scheme that balances safety with practical constraints.
Assessment in HV
Can your drug's pharmacodynamic effects be adequately evaluated in healthy volunteers?
No - requires disease state or disease-specific biomarkers to assess
Yes - fully assessable in healthy volunteers
Partially - some effects observable in HV, but key effects require patients
Critical gap. Consider a traditional pathway or an abbreviated MAD study.
Partial assessment weakens the case. You will need to articulate which effects require patients and why those are critical.
Why it matters This is a critical factor. If you can fully assess your drug's pharmacodynamic effects in healthy volunteers, there's little scientific rationale for skipping those studies. The strongest case for alternative pathways is when the drug can ONLY be evaluated in patients with the disease.
Key scientific justification. Your drug's effects can only be assessed in patients with the disease, which strongly supports going directly to patient studies.
Preclinical safety
How would you rate your preclinical safety data?
Why it matters A robust preclinical package is non-negotiable for alternative pathways. Without comprehensive safety data and wide safety margins, you are exposing patients to unacceptable risk. Regulators will scrutinize your preclinical data heavily if you are proposing to skip HV studies.
Comprehensive GLP toxicology with wide safety margins (>10x) and robust PK/PD modeling
Limited safety data or narrow margins (<3x)
Preclinical program still incomplete
See your results
Standard toxicology package with adequate safety margins (3-10x)
Critical gap. Makes it too risky. Complete your preclinical program before considering this approach. More traditional path is strongly recommended.
Essential foundation in place.
Adequate but not ideal. Standard packages may support hybrid approaches but make it harder to justify skipping HV studies entirely.
Your results
Your program has multiple factors that support an alternative pathway. With proper planning and risk mitigation, skipping MAD studies may be feasible. Discuss your specific program with our experts. We'll help you: Evaluate your complete data package Develop regulatory strategy Design the optimal approach for your program Assess risks and mitigation plans
Your program is a strong candidate for an alternative pathway
Discuss your program with our experts
Your program has some factors that support alternative pathways, but also some gaps. Consider hybrid options or strengthening identified areas. Discuss your specific program with our experts. We'll help you: Evaluate hybrid pathway options Identify gaps to strengthen Develop regulatory strategy Design the optimal approach for your program
Your program should consider a hybrid approach
Based on your responses, an alternative pathway is not advisable at this time. Focus on traditional development with an optimized MAD study design. Discuss your specific program with our experts. We'll help you: Optimize your MAD study design Develop regulatory strategy Accelerate your development timeline Assess alternative efficiencies
A traditional pathway is recommended for your program
