The first testing of a drug to be approved in Canada, or in the US by the FDA, or for the EU's drug agency, requires giving the drug at various doses to healthy persons. We often are taught that these are very much volunteers, who participate for only good reasons.
If there are bad side effects or even dangerous consequences to new drugs, then these factors must be known or clinical trials on sick persons might cause great harm. Yet, we seem to experience the removal of some drugs from the market long after their approved use causes some severe adverse effects. The adverse effects signal tends to take a couple of years or more before it becomes apparent that the drug should never have been approved because of its severe side effects. How can this be missed in Phase-I? This is how.