Drug regulation farther down in the distribution system came under scrutiny in 1955, when FDA undertook a pilot study of adverse drug reaction reporting. In cooperation with the American Society of Hospital Pharmacists, the American Medical Association, and others, the study focused on reactions reported by hospitals and pharmacists. Adverse reaction reporting at this time was voluntary and reports normally were scarce.

The emergence of fatal blood dyscrasias associated with chloramphenicol in the early 1950s led to the search for better adverse reaction reporting.

This study blossomed into a more ambitious effort in 1957, a large-scale system for voluntary reporting to assist with post-marketing evaluation of new drugs. By 1963 the study had evolved into a voluntary reporting system with almost 200 participating hospitals.