OVERVIEW
Companies developing novel drugs or biologic products for rare diseases or other life-threatening diseases can now plan clinical studies for Investigational New Drugs (INDs) to establish their drug or biologic candidate’s effectiveness and explore strategies reduce to their time to market with New draft guidance from FDA.
GUIDANCE: ‘Providing Evidence of Effectiveness of Human Drug and Biologic Products’
The US Food and Drug Administration has released draft guidance (FDA-2019-D-4964) in December 2019, building on top of FDA’s guidance, ‘Providing Evidence of Effectiveness of Human Drug and Biologic Products’. The new draft provides guidance on using a single adequate and well-controlled clinical trial and confirmatory evidence to be used as to support approval of a drug or biologic product.
FDA GUIDANCE AIMS AT OFFERING ADDITIONAL FLEXIBILITY
The new guidance has been provided in lieu of novel mechanisms of drugs and biologic products developed over past two decades with advancement of scientific knowledge. The guidance aims at offering additional flexibility under following circumstances,
- In case of life-threatening or severely debilitating diseases with an unmet medical need
- Rare diseases
- In cases where it is not ethical or feasible to conduct clinical studies on human subjects
CLINICAL TRIAL DESIGNS
The guidance discusses multiple types of clinical trial designs in additional to most rigorous clinical study designs such as randomized, double-blinded, controlled superiority trials that may be considered to establish evidence for effectiveness of drugs or biologic products. It also discusses scenarios where more than one study design may be required to substantiate the evidence or a single study design with multi-center studies.
TABLE 1 : QUANTITY OF CLINICAL EVIDENCE BY FDA TO ESTABLISH EFFECTIVENESS
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Quantity of Clinical Evidence Expected by FDA to Establish Effectiveness |
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Meeting the substantial evidence standard based on two adequate and well controlled clinical investigations |
Meeting the substantial evidence standard based on one adequate and well controlled clinical investigation plus confirmatory evidence |
Meeting the substantial evidence standard for a new population or a different dose, regimen, or dosage form, based on reliance of FDA’s previous finding of effectiveness of an approved drug when scientifically justified and legally permissible *In cases where FDA can rely on its previous findings of approved drug provided it is scientifically justified and legally permissible |
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Two adequate and well-controlled clinical investigations *When there is a need for substantiation of results |
One adequate and well-controlled clinical investigation on a new indication for an approved drug, supported by existing adequate and well-controlled clinical investigation(s) that demonstrated the effectiveness of the drug for its other, closely related approved indication(s) |
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One adequate and well-controlled large multi-center trial that can provide substantial evidence of effectiveness *In cases where the outcome may not be considerably different from two adequate studies |
One adequate and well-controlled clinical investigation supported by data that provide strong mechanistic support |
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One adequate and well-controlled clinical investigation with compelling results, supported by additional data from the natural history of the disease |
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One adequate and well-controlled clinical investigation of the new drug, supported by scientific knowledge about the effectiveness of other drugs in the same pharmacological class |
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Quantity of Clinical Evidence Expected by FDA to Establish Effectiveness
Meeting the substantial evidence standard based on two adequate and well controlled clinical investigations
Meeting the substantial evidence standard based on one adequate and well controlled clinical investigation plus confirmatory evidence
Meeting the substantial evidence standard for a new population or a different dose, regimen, or dosage form, based on reliance of FDA’s previous finding of effectiveness of an approved drug when scientifically justified and legally permissible
*In cases where FDA can rely on its previous findings of approved drug provided it is scientifically justified and legally permissible
Two adequate and well-controlled clinical investigations
*When there is a need for substantiation of results
One adequate and well-controlled clinical investigation on a new indication for an approved drug, supported by existing adequate and well-controlled clinical investigation(s) that demonstrated the effectiveness of the drug for its other, closely related approved indication(s)
One adequate and well-controlled large multi-center trial that can provide substantial evidence of effectiveness
*In cases where the outcome may not be considerably different from two adequate studies
One adequate and well-controlled clinical investigation supported by data that provide strong mechanistic support
One adequate and well-controlled clinical investigation with compelling results, supported by additional data from the natural history of the disease
One adequate and well-controlled clinical investigation of the new drug, supported by scientific knowledge about the effectiveness of other drugs in the same pharmacological class
RESOURCES
- FDA
- WHITEPAPER:Establishment Registration with the FDA.
- WHITEPAPER: US Representative
- WHITEPAPER: US Medical Devices
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