Science - USA (2020-01-17)

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242 17 JANUARY 2020 • VOL 367 ISSUE 6475 sciencemag.org SCIENCE

the drug was ineffective and caused suicidal

thoughts in teenagers, yet encouraged doc-

tors to prescribe it for young people.

Registration was only required initially for

trials of treatments for serious or life-threat-

ening diseases. But the 2007 law, the Food

and Drug Administration Amendments Act,

required sponsors to register a much broader

range of trials within 21 days of enrolling the

first patient, and to post summary results,

adverse events, and other data to Clinical-

Trials.gov within 1 year of collecting the last

patient data. Although many trials, such as

industry-sponsored early-stage evaluations

of drug safety, are exempt from reporting,

about 326,000 have been registered, and re-

sults have been posted for more than 40,000.

Yet until 2015, even the most active in-

vestigators at clinical research institutions

treated the law more as a suggestion—not

surprising given that the government en-

forced no penalties and did not publicly iden-

tify violators. A report on the news website

STAT by this author and Talia Bronshtein first

drew significant attention to specific trial

sponsors—companies, government agencies,

universities, and individuals—that routinely

ignored reporting requirements. It sparked

immediate improvement, according to NIH.

(Those same authors documented some of

that improvement in a 2018 STAT article.)

At a 2016 press briefing, NIH and FDA

rolled out the final rule, aimed at boost-

ing even greater compliance with the 2007

law. It took effect in January 2017, with first

deadlines for results, and ostensibly enforce-

ment, 1 year later. Then–FDA Commissioner

Robert Califf said it would thereafter “be

pretty hard to hide that you are doing a clini-

cal trial or hide the result.” FDA, he vowed,

was finally prepared, if necessary, to enforce

the daily $10,000 penalty for noncompliance

allowed under the law. (Adjusted for infla-

tion, that figure recently rose above $12,000.)

“I don’t think anybody wants to be on

the wall of shame,” NIH Director Francis

Collins said at the press event, promising

that NIH would publicly flag reporting viola-

tions on ClinicalTrials.gov itself.

“We are serious about this,” Collins said,

threatening for the first time to enforce

provisions of the 2007 law that allow NIH

to rescind funding to grantees who violate

the statute. “It’s hard to herd cats, but you

can ... take their food away,” he said. “This

is about maintaining the trust that we have

with participants in clinical trials. ... If we

fail to live up to that expectation, then that

is an ethical failure.”

Three years later, TrialsTracker conser-

vatively estimates that FDA could have

collected more than $6 billion in Clinical-

Trials.gov penalties so far. The agency has

yet to demand a single dollar. And despite CREDITS: (GRAPHIC) N. DESAI/

SC

IENCE

; (DATA)

CLINICALTRIALS.GOV/TRIALSTRACKER

Academic/nonproft

Federal government

Industry

Avg.

days

late

Total

trials

Reported on time or early Reported late Not reported Quality problems

Massachusetts General Hospital

Mayo Clinic

Memorial Sloan Kettering Cancer Center

University of North Carolina, Chapel Hill

University of California, San Francisco

Duke University

University of Pennsylvania

Emory University

UT Health Science Center, Houston

Wash. Univ. School of Medicine in St. Louis

University of Chicago

Stanford University

Johns Hopkins University

University of Washington

Wake Forest University Health Sciences

University of Virginia

Sidney Kimmel Comp. Cancer Center

University of Michigan

New York State Psychiatric Institute

Columbia University

Yale University

Dana-Farber Cancer Institute

Icahn School of Medicine at Mount Sinai

Indiana University

University of Colorado, Denver

Medical University of South Carolina

Montefore Medical Center

Northwestern University

University of Alabama, Birmingham

University of Wisconsin, Madison

National Cancer Institute

Natl. Inst. of Allergy and Infectious Diseases

VA OSce of Research and Development

Natl. Heart, Lung, and Blood Institute

Novartis Pharmaceuticals

Gilead Sciences

POzer

GlaxoSmithKline

HoVmann-La Roche

AstraZeneca

Eli Lilly and Company

Allergan

Amgen

Bristol-Myers Squibb

Merck & Co.

SanoO

Alcon

AbbVie

Celgene

Novo Nordisk

Boehringer Ingelheim

Johnson & Johnson Vision Care

Bayer

Janssen Research & Development

Teva Pharmaceutical Industries

MD Anderson Cancer Center 89 128

63

57

43

38

37

36

34

30

29

29

28

26

25

24

24

23

21

21

20

19

19

18

17

17

17

16

16

15

15

15

86

24

22

15

65

53

48

46

44

41

39

25

25

25

25

24

23

22

22

19

18

17

16

16

16

140

156

185

66

179

140

207

74

64

108

204

187

16

175

98

281

142

79

195

182

116

189

112

123

195

141

144

214

59

145

134

51

84

119

41

23

17

25

43

16

60

0

0

0

0

578

0

0

4

23

0

0

0

1

124

Reporting problems
Science analyzed ClinicalTrials.gov records of all clinical trials with results required to be reported between
18 January 2018 and 25 September 2019. The chart, covering trial sponsors with 15 or more results due in that
window or reported early, shows that some results deposited were not posted due to quality lapses. It also
highlights that pharma’s record has been markedly better than that of academia and the federal government.

Published by AAAS