Causality, Impartiality and Evidence-Based Policy - Mechanism and Causality in Biology and Economics - page 203

4 External Validity and Impartiality in Regulatory RCTs
Today, FDA is probably the institution that makes the most systematic use of RCTs
for regulatory purposes in the world, but has not always been so. Between 1900 and
1950, expert clinical judgement was the main criterion in the assessment of the
properties of pharmaceutical compounds in the United States as well as in other
countries such as Britain. An experienced clinician would administer the drug to a
series of patients he would consider likely to benefit. His or her conclusions would
be presented as a case report, informing of the details of each patient's reaction to
the treatment. The regulatory authorities in the United States and Britain arranged
official drug testing depending on the standards adopted by the research community
within their respective medical professions. Until the 1960s, regulatory decisions
were fundamentally based on expert judgements of this sort. Clinical judgement
came to be discredited in the United States because a group of methodologically
minded pharmacologists took over the FDA and imposed their views on the
superiority of RCTs through regulatory means. This was the triumph of mechanical
objectivity against expert judgement.
During the 1960s and 1970s, RCTs became mandatory for regulatory decisions
in different degrees. In the United States, before the 1960s, the FDA was entitled
only to test the safety but not the efficacy of pharmaceutical compounds. In the late
1950s, there were voices in the FDA demanding stricter testing standards linking
safety and efficacy, under increasing public mistrust in the pharmaceutical industry,
prompted in part by the thalidomide scandal.
Under the trade name Contergan , one million West Germans consumed thalido-
mide as a sedative in the early 1960s and many more people around the world after
that. Reports showing an association between the drug and peripheral neuropathy
were soon published in medical journals. Later reports of serious birth defects when
the drug was consumed by pregnant women surfaced. Only then did the manufac-
turer withdraw the drug from European markets. Eight thousand babies had been
already born with severe deformities. At that point, there was no clear regulatory
standard about the safety of a compound, neither in the United States nor in Europe.
The thalidomide scandal gave them the opportunity to put their views in effect in
the 1962 Drug Efficacy Amendment to the Food, Drug and Cosmetics Act. It
required from the applicant 'adequate and well-controlled clinical studies' for
proof of efficacy and safety (although the definition of a well-controlled investiga-
tion would not be clarified until 1969, when it was formally quantified as two well-
controlled clinical trials plus one prior trial or posterior confirmatory trial). It has
been claimed, correctly in our view, that this set of regulations created the modern
clinical trial industry (Carpenter and Moore 2007 ). In the following three decades,
pharmaceutical funding would boost the conducting of RCTs (by the thousands) in
the United States and abroad.
The regulatory approach of the FDA surely constitutes a canonical instance of an
evidence-based policy or, more precisely, an RCT-based policy. It is worth noting