University of South Florida (USF) Distinguished Professor Benjamin Djulbegovic, MD, PhD, has
studied the ethics of randomized clinical trials and their effectiveness
in evaluating the outcomes of new treatments for decades.
Now, in a paper published Aug. 22 in the top journal Nature,
Dr. Djulbegovic and colleagues report that on average new treatments
work better than existing ones just over half the time. On scientific
and ethical grounds, they say, the randomized controlled trial (RCT)
system’s little more than 50-50 success rate over the past half century
is evidence that the system is working as intended.
The researchers analyzed 860 phase III published and unpublished RCTs
performed by academic institutions or pharmaceutical companies. These
trials collectively involved more than 350,000 patients.
“Our retrospective review of more than 50 years of randomized trials
shows that they remain the ‘indispensable ordeals’ through which
biomedical researchers’ responsibility to patients and the public is
manifested,” the researchers conclude. “These trials may need tweak and
polish, but they’re not broken.”
People who consent to participate RCTs are willing to be randomly
allocated to new or existing treatments. While RCTs are considered the
gold standard for comparing the effects of one treatment to another, the
gradual progress they yield can seem frustratingly slow — particularly
for patients with poor standard treatment options.
Yet, the genuine uncertainty associated with individual RCTs has been
vital to the gains in therapeutics, said Dr. Djulbegovic, professor of
medicine and oncology at the USF Health Morsani College of Medicine and
Moffitt Cancer Center. If there was significant likelihood that one
treatment in a comparison was better than the other, it would be
unethical to deny some patients the superior treatment, and
well-informed patients would probably refuse to participate in the
study, he said.
Incremental advances in treatment generated by RCTs over time – such
as childhood leukemia cure rates moving from zero to 80 percent even
though only 2 to 5 percent of new treatments provided a breakthrough –
have translated into important improvements in health and lifespan, the
authors say. However, they suggest trials could still benefit from more
rigorous design, implementation and reporting –with widespread
publication of trial results, including negative findings.
Source: University of South Florida
