## Facts

- Edison Pharmaceutical Co. sponsored a new drug application (NDA) for Cothyrobal, an injectable combination of thyroid extract, sodium levothyroxine, and vitamin B12, intended to treat hypercholesterolemia and hypothyroidism.
- Edison filed the NDA in May 1969; the FDA denied the application in December 1969 for failing to meet statutory submission requirements and for lack of adequate proof of effectiveness.
- FDA maintained that approval required “adequate and well-controlled” clinical investigations, including double-blind controlled studies comparing Cothyrobal with levothyroxine.
- Edison refused to conduct double-blind comparison studies, asserting that giving levothyroxine without B12 would be unsafe and unethical.
- In earlier appellate litigation, the court required an evidentiary hearing to determine whether such double-blind studies could be conducted safely and to decide issues relevant to approvability.
- On remand, an administrative law judge (ALJ) found limited double-blind testing could be done safely and concluded Edison’s submitted studies did not demonstrate safety and effectiveness under the FDCA.
- The ALJ excluded certain testimonial materials offered to show efficacy (e.g., anecdotal or uncontrolled clinical impressions) as insufficiently reliable under the governing evidentiary framework.
- The Commissioner adopted the ALJ’s findings and issued a final order refusing NDA approval; Edison petitioned for judicial review.

## Issues

1. Whether substantial evidence supported the Commissioner’s refusal to approve the NDA, including findings that Edison had not provided adequate and well-controlled proof of safety and effectiveness and that limited double-blind testing was feasible and safe.
2. Whether FDA complied with the court-ordered “full evidentiary hearing,” or instead violated the mandate by excluding Edison’s proffered efficacy testimony.

## Decision

- The court denied the petition for review and affirmed the Commissioner’s final order refusing NDA approval.
- The court held the refusal was supported by substantial evidence on the record as a whole.
- The court held FDA provided the required evidentiary hearing and permissibly excluded unreliable or non-probative evidence under the applicable standards.
- The court deferred to FDA’s scientific judgment regarding the necessity and design of controlled clinical studies, where supported by the administrative record.

## Legal Principles

- Under the FDCA, the NDA sponsor bears the burden to establish safety and effectiveness through “substantial evidence,” generally requiring adequate and well-controlled clinical investigations.
- A reviewing court upholds FDA’s denial of an NDA if the agency’s findings are supported by substantial evidence on the record as a whole.
- FDA may require controlled, comparative clinical studies when the record supports their feasibility and safety, even when the sponsor raises ethical or medical objections.
- A court-ordered “full evidentiary hearing” requires a fair opportunity to present relevant and reliable evidence, but does not eliminate the agency’s authority to exclude evidence that lacks probative value under statutory and regulatory standards.

## Conclusion

The D.C. Circuit upheld FDA’s refusal to approve Cothyrobal because substantial evidence supported the agency’s determination that Edison failed to provide adequate and well-controlled proof of effectiveness and that limited double-blind testing could be conducted safely; the court also rejected claims that evidentiary exclusions deprived Edison of the mandated hearing.


Edison Pharmaceutical Co. v. Food & Drug Admin., 600 F.2d 831 (D.C. Cir. 1979)