25 Ocak 2014
FDA ilaç onaylarında standart davranıyor mu?
Kaynak: USA Today, U.S. News & World, The Wall Street Journal, Bloomberg, Breitbart, The Washington Post, JAMA
2005-2012 arasında yapılan çalışmalar bakılmış. Genelde 206 toplam
endikasyonda her endikasyon başına 2 çalışma varken, 74 endikasyon 1
pivotal çalışma ile onay almış. Çalışmaları %89.3u randomize iken,
%79.5i çift kör, ve %87.1i aktif ya da plasebo ile karşılaştırmış.
Çalışmalar alınan hasta sayısı 270-1550 arasında.
endikasyonda 6 aydan daha fazla süren bir pivotal çalışma kullanılmış.
91 çalışmada bir biyomarker son nokta. 67 çalışmada ise klinik sonuç son
nokta olarak kullanılmış.
Kanser ilaçları genellikle tek çalışma
ile onaylanmış. Psikiyatrik, kardiyovasküler ve diyabet ve hipertansiyon
ilaçları en az 3 çalışma ile onay almış. Kronik hastalıkların
çalışmaları 1 yıldan az sürdüğü için bu ilaçların uzun süreli
etkinlikleri ve güvenlikleri hakkında tereddüt var.
Ref: USA Today, U.S. News & World, The Wall Street Journal, Bloomberg, Breitbart, The Washington Post, JAMA
Study results published Tuesday in JAMA suggest there is wide
variation in the quality of clinical trial evidence used by the FDA as
the basis for recent new drug approvals. Senior author Joseph Ross said
"some [drugs] are approved on very robust evidence, and some are based
on preliminary evidence," adding that "there is a lot of nuance at the
time of approval that isn't well communicated to patients."In order to characterise pivotal efficacy trials for newly approved
novel therapeutic agents, investigators conducted a cross-sectional
analysis of publicly available FDA documents for all such drugs approved
between 2005 and 2012. During that period, the US regulator approved
188 novel therapeutic agents for 206 indications based on 448 pivotal
efficacy studies. Findings showed that the median number of pivotal
studies per indication was two, although 74 indications gained FDA
clearance based on a single pivotal trial. The authors also noted that
89.3 percent of the studies were randomised, 79.5 percent were
double-blinded and 87.1 percent used either an active or placebo
comparator. The number of patients enrolled in the trials ranged from
270 to 1550, with the median number per indication among all pivotal
trials being 760.The study found that at least one pivotal trial lasting six months
or more supported the approval of 68 indications. Trials using surrogate
endpoints, which were defined as any endpoint using a biomarker
expected to predict clinical benefit, formed the exclusive basis of
approval for 91 indications, while clinical outcomes were the basis for
approval for 67 indications, and clinical scales for 36 indications.
"This reliance on surrogate outcomes leaves patients and physicians to
extrapolate clinical benefits from trials, again raising questions about
the certainty of medications' benefits in practice," the researchers
said, with lead author Nicholas Downing noting that many studies "were
small, short, and focused on laboratory values, or some other surrogate
metric of effect, rather than clinical endpoints like death." Further, study features differed by therapeutic and indication
characteristics. The authors found that, for example, most drugs
authorised for cancer indications were approved on the basis of a single
trial, whereas drugs for psychiatric indications, cardiovascular
disease, diabetes, or hyperlipidaemia often relied on at least three
trials. They also found that most studies evaluating drugs for chronic
treatment lasted less than one year, "raising questions about the
certainty of these medications long-term efficacy and safety."Still, the researchers noted that the FDA's "regulatory flexibility
allows for a customised approach to approval, including the ability to
rapidly approve potentially effective therapies for life-threatening
diseases." In an accompanying editorial, Steven Goodman said that "the
FDA walks a tightrope, and until now we haven't had a huge amount of
information about how they're doing that balancing act." He said the
criteria used by the FDA "could be perfect, in that [the agency is]
being flexible and allowing innovation and getting lifesaving drugs
through to market," but that, conversely, "they could be making
decisions too precipitously and allowing potentially dangerous
medications through. It's a difficult balancing act that requires
constant monitoring." FDA spokeswoman Stephanie Yao said that "the agency applies the
same statutory approval standards of safety and efficacy to all drugs,
but uses regulatory flexibility in applying those standards." Meanwhile, a third study, which was conducted by the FDA and whose
results were also published in JAMA, examined why the agency delayed or
rejected approval of new medications tested between 2000 and 2012.
Findings indicate that these regulatory outcomes were often caused by
problems with setting the correct dosage, choosing the appropriate
patients to include in the trial, or establishing proper endpoints. The
authors suggested that "early and frequent dialogue between the FDA and
drug sponsors addressing critical aspects of study design
potential to reduce delays in the approval of new drugs."