COMING OFF THE GOLD STANDARD
CAN GET THE JOB DONE

By Helen Gavaghan*

In the world of drug development the randomised, double-blind, placebo-controlled clinical trial
has long been considered the most professional way to complete the process of getting a drug
to market. It is often referred to as the "Gold Standard". Yet it can be a crude tool. In the
February 2nd 2017 issue of the New England Journal of Medicine Richard Moscicki MD, from
the US Food and Drug Administration's Center for Drug Evaluation and Research, outlines with
a Ph.D colleague from industry examples of alternate regulatory strategies for drug approval.
Their context is mainly innovative product development by small companies.

Sometimes it is the ethics of the situation, sometimes the nature of the disease, or advances in
ability to identify subgroups as appropriate therapeutic targets which prompts
regulators to accept an alternate to the "gold" standard in a drug development strategy.

Take the rare disease, Pompe. In 2006 the US FDA authorised a treatment known as
Myozyme for clinical use. During the regulatory process instead of administering placebo to a
control group, the researchers reviewed medical charts to locate an historic cohort matched for
age and the treatment options available to the historic group. There were 18 patients in the
trial who were being compared with the retrospectively identified control group. A large positive
effect was observed in those (babies) administered Myozyme. On the basis of that 18-patient
group and those findings the US FDA approved the drug.

Ethics drove selection of the trial strategy because early clinical trials (which would have been
the ones dealing with such issues as teratogenic effects, for example) had suggested the trial
drug could help the babies otherwise very likely to die before their first birthday. The drug is the
product of recombinant DNA. In Pompe's disease there is a deficit of a normally occurring
molecule, known as acid a galactosidase (GAA). GAA breaks down lyosomal glycogen into
glucose for energy. In GAA's absence glycogen accumulates in muscle, leading to cardio-
myopathy, hypotonia and generalised muscle weakness.

Other alternates to the "gold standard" include: identifying a surrogate endpoint to enable a
more homogenous and smaller patient subgroup (it helps to have identifiable clear pheno-
types); and identifying a genetic marker indicating those patients most likely to benefit from a
therapy seeking regulation. Drs Moscicki and his industry co-author describe how these
approaches to drug development have been examined and applied at the FDA. HG
___________________
Drug-Development Challenges for Small Biopharmaceutical Companies. Richard A. Moscicki,
M.D., and P.K. Tandon, Ph.D. 2nd February 2017. N Engl J Med 2017; 376:469-47 DOI:
10.1056/NEJMra1510070

Among other things Helen Gavaghan is former editor of international medical devices and diagnostics Newsletter,
Clinica, former Washington-DC biomedical research policy correspondent of Nature, former US correspondent for
Le Journale International de Medecin, and former UK correspondent for the Paris-based magazine, Biofutur.

Issue 1 (Jan-Mar), 2017............................................Science, People & Politics ISSN 1751-598X print and online

COMING OFF THE GOLD STANDARD CAN GET THE JOB DONE

COMING OFF THE GOLD STANDARD
CAN GET THE JOB DONE