A comparison of the Food and Drug Administration’s and Health Canada’s regulatory decisions about failed confirmatory trials for oncology drugs: an observational study

Background: Oncology drugs are frequently approved on the basis of surrogate outcomes that require further trials to confrm the benefts, but at times these trials fail and regulators need to decide whether to withdraw approval for the indication and/or to remove the drug from the market. This study compares decisions by the Food and Drug Administration and Health Canada about oncology drugs that were approved using either Accelerated Approval (FDA) or Notice of Compliance with conditions (NOC/c, Health Canada) and that failed confrmatory trials. Methods: Drug/indications approved by the FDA through its Accelerated Approval Pathway and that later failed confrmatory studies were identifed from a published study and additional information on these drugs was collected from Drugs@FDA. Health Canada websites were searched on September 11, 2021 for the same group of drugs to determine if they were approved in Canada under the NOC/c pathway for the same indication as in the US. Information from both the FDA and Health Canada about these products was entered into an Excel spreadsheet. Decisions about whether to withdraw the drugs or remove the failed indication for the drug and requirements for confrmatory studies were compared. In addition, the dates of decisions by the two agencies were compared. Results: Ten drug/indications were available for comparison. Regulatory decisions were similar in 4 cases, diferent in 1 case and could not be determined in the remaining 5, in 1 case because decisions were pending in both countries and in the other 4, because the NOC/c had not been fulflled in Canada. The requirements for the confrmatory studies were similar in both countries. Decisions were made earlier in the United States. Conclusions: This study shows that decisions made by Health Canada and the FDA about whether to withdraw a drug or remove a failed indication when drug/indications fail a confrmatory trial are usually similar, although the sample size on which this conclusion is made is small. The clinical implications of these similarities and diferences should be explored.

Background: Oncology drugs are frequently approved on the basis of surrogate outcomes that require further trials to confrm the benefts, but at times these trials fail and regulators need to decide whether to withdraw approval for the indication and/or to remove the drug from the market. This study compares decisions by the Food and Drug Administration and Health Canada about oncology drugs that were approved using either Accelerated Approval (FDA) or Notice of Compliance with conditions (NOC/c, Health Canada) and that failed confrmatory trials. Methods: Drug/indications approved by the FDA through its Accelerated Approval Pathway and that later failed confrmatory studies were identifed from a published study and additional information on these drugs was collected from Drugs@FDA. Health Canada websites were searched on September 11, 2021 for the same group of drugs to determine if they were approved in Canada under the NOC/c pathway for the same indication as in the US. Information from both the FDA and Health Canada about these products was entered into an Excel spreadsheet. Decisions about whether to withdraw the drugs or remove the failed indication for the drug and requirements for confrmatory studies were compared. In addition, the dates of decisions by the two agencies were compared. Results: Ten drug/indications were available for comparison. Regulatory decisions were similar in 4 cases, diferent in 1 case and could not be determined in the remaining 5, in 1 case because decisions were pending in both countries and in the other 4, because the NOC/c had not been fulflled in Canada. The requirements for the confrmatory studies were similar in both countries. Decisions were made earlier in the United States. Conclusions: This study shows that decisions made by Health Canada and the FDA about whether to withdraw a drug or remove a failed indication when drug/indications fail a confrmatory trial are usually similar, although the sample size on which this conclusion is made is small. The clinical implications of these similarities and diferences should be explored.