White Paper

The State of Global
Clinical Trial Disclosure:

What Noncompliance Penalties Are
in Place, and How They Are Enforced

March 2023

Contents

Introduction 03
Industry Organizations 

04

The Global Landscape 

05

In Conclusion 19

2

March 2023 

Copyright ©️ 2023 Pharma Intelligence UK Limited, a Citeline company (Unauthorized photocopying prohibited)Introduction

By Darcy Grabenstein

The coronavirus pandemic put clinical trials inthe spotlight — or hot seat, depending on one’s
perspective. Around the globe pressure camefrom multiple fronts: regulatory agencies, thepublic, patients, advocates, pharmaceuticalindustry watchdogs ,and investors all clamoredfor increased clinical transparency. The push
for accountability has not abated for study
sponsors to publish results in a timely manner.
However, just as there are numerous regulatory
agencies and guidelines (approximately 90
countries have requirements related to thedisclosure of clinical trial data made publicly
available on over 30 clinical trial registries),
enforcement of clinical trial disclosure
requirements varies greatly.
While study sponsors have come under fire for
failure to disclose trial information, so too haveregulatory agencies. The US National Institutesof Health (NIH) failed to ensure the timely
reporting of results in roughly half of the clinical
trials it funded in 2019 and 2020, according toa report released by the Department of Healthand Human Services’ Office of Inspector
General. In some cases, the agency allowed
noncompliant researchers to launch new trials.
A 2022 Health and Human Services inspector
general’s office audit of the NIH revealed thatof 72 intramural and extramural trials, only
35 submitted results were on time, 12 were

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March 2023

submitted late, and 25 never submitted. The
report reads: “NIH did not have adequate
procedures for ensuring that responsible parties
submitted the results of clinical trials, took
limited enforcement action when there wasnoncompliance, and continued to fund new
research of responsible parties that had not
submitted the results of their completed clinical
trials.”Its recommendation included that the NIH “takeenforcement actions against responsible parties
that are late in submitting trial results or do not
submit results.”
The European Medicines Agency (EMA) refused
to release major documents containing clinicaldata, including adverse effects, produced bypharmaceutical companies, according to a 2022
report. The report concluded: “The European
Parliament and the European Commission,
which are responsible for adherence to theinstitutional and regulatory principles of the EU,should also ensure that clinical study reports are
published in their entirety, as required by theClinical Trials Regulation [CTR].”That said, lack of transparency at a regulatory
agency does not diminish the sponsor’s
responsibility to comply with disclosure
deadlines.

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The State of Global Clinical Trial Disclosure:
What Noncompliance Penalties Are in Place, and How They Are Enforced

Industry Organizations
Many pharmaceutical industry groups haveissued statements or developed policies
regarding clinical trial disclosure. Following areseveral organizations that have taken a stanceon transparency.
The International Committee of Medical
Journal Editors (ICMJE) “requires, andrecommends that all medical journal editors
require, registration of clinical trials in a public
trials registry at or before the time of first patient
enrollment as a condition of consideration for
publication.” In addition, the ICMJE recommends
that journals publish the trial registration number
at the end of the abstract.
The trade organization International
Federation of Pharmaceutical Manufacturers& Associations (IFPMA) provided thisstatement on disclosure: “The innovative
pharmaceutical industry is committed to thetransparency of clinical trials that are sponsoredby our member companies. We therefore
commit to a set of principles regarding thedisclosure of information relating to clinical trials
we sponsor and appeal to all sponsors of clinical
trials to commit to keeping these registries
accurate and up to date.”
The Pharmaceutical Research andManufacturers of America (PhRMA), in
response to a request for comment, released
this statement: “PhRMA members arecommitted to enhancing public health andadvancing the development of medicines bysponsoring and conducting clinical researchthat fully complies with all legal and regulatory
requirements. Further, our Principles for
Responsible Clinical Trial Data Sharing set forth
PhRMA members’ commitment to enhancing
public health through responsible sharing ofclinical trial data in a manner that safeguards
the privacy of patients, respects the integrityof national regulatory systems, and maintains
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March 2023 

incentives for investment in biomedical
research.”
In May 2017, over 20 international regulatory
agencies and related organizations signed
a joint statement from the World HealthOrganization (WHO) on public disclosureof results from clinical trials. The signatories
agreed to the following: “Within 12 months ofbecoming a signatory of this statement, weeach pledge to develop and implement a policy
with mandated timeframes [12 months fromprimary study completion] for prospective
registration and public disclosure of theresults of clinical trials that we fund, co-fund,sponsor or support. We each agree to monitor
registration and endorse the development ofsystems to monitor results reporting on an
ongoing basis. We agree to share challenges
and progress in the monitoring of these policies.
We agree that transparency is important andtherefore the outputs from the monitoringprocess will be publicly available.”
A 2022 paper co-authored by Till Bruckner, PhD,
founder of TranspariMED, a nonprofit working
to end evidence distortion in medicine, posed
this question: Do European medical research
funders require grantees to register and reportclinical trials in line with WHO best practices?
This cross-sectional study of the 21 largest
nonmultilateral public and philanthropic funders
in Europe found that funders implemented amean of 36% of WHO best practices in clinical
trial transparency.
A total of 14 funders (66.7%) mandated
prospective trial registration and six funders(28.6%) required that trial results be madepublic on trial registries within 12 months of trial
completion. Less than half of funders actively
monitored whether trials were registered (9funders [42.9%]) or whether results were madepublic (8 funders [38.1%]).

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The State of Global Clinical Trial Disclosure:
What Noncompliance Penalties Are in Place, and How They Are Enforced

The Global LandscapeLet’s take a look at a broad spectrum of
global regulations, whether penalties exist fornoncompliance and, if so, whether they arebeing enforced. Citeline reached out to all major
regulatory agencies; those listed below provided
requested updates.

NORTH AMERICAThe USAs in all areas the FDA regulates, the agency’s
goal is to achieve voluntary compliance withapplicable legal requirements. The FDA’s
compliance activities related to theClinicalTrials.gov requirements provide theopportunity for responsible parties to takevoluntary corrective actions before the agency
proceeds with a civil or criminal enforcement
action. The agency uses a risk-based approachto compliance and enforcement to prioritize
the greatest risks to public health and works
with responsible parties to help them voluntarily
comply.
The FDA is authorized to seek civil money
penalties for violations of the ClinicalTrials.gov
requirements. Responsible parties that failto submit clinical trial results information
for certain applicable clinical trials to theClinicalTrials.gov databank could also be
subject to an injunction and/or criminal
prosecution. Penalties of $13,327 (maximum
adjusted penalty) are in place for all violations
adjudicated in a single proceeding and, if aviolation is not corrected within 30 calendar
days following notification of such violation,
the law provides for an additional civil money
penalty for each day the violation continues
until it is corrected.

5March 2023 

The FDA is required by law to issue a Notice ofNoncompliance to a responsible party whom
the FDA has determined has failed to comply
with this requirement. To date, the FDA has
issued 92 Pre-Notice Letters and four Noticesof Noncompliance to encourage compliancewith the ClinicalTrials.gov requirements. The
four recipients of Notices of Noncompliancesubmitted the required clinical trial information,a testament to the effectiveness of enforcement,
and the agency did not pursue civil money
penalties against them. The FDA has not yet
pursued civil money penalties against any
responsible parties.
However, the FDA has defined a limited
approach to identify violations. A violation may
be detected during a Bioresearch Monitoring(BIMO) inspection or based on an evaluationof complaints received by the agency. FDA
enforcement to date is perceived as being
extremely slow. Even though over 4,000 clinical
trial results are missing in the US (24% of trials
that require results under the Final Rule), the
FDA is currently only sending out two notices
per week. “Just put 10,000 letters in the mail,”advises TranspariMED’s Bruckner. “Sending out
letters to people who break the law is not adifficult regulatory decision.”
While the US may be one of the few countries
taking baby steps to enforce clinical trial
disclosure, some say more enforcement isneeded.

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The State of Global Clinical Trial Disclosure:
What Noncompliance Penalties Are in Place, and How They Are Enforced

US Academia Brings Up Its Grades, After‘Report Card’ Goes Public
Navya Dasari is a woman on a mission. A
student at New York University’s School ofLaw, she is a member of the North American
Coordinating Committee for Universities Allied
for Essential Medicines (UAEM). The healthjustice organization focuses on access to
medications and drug pricing.
She said the issue of clinical trial results
reporting “struck me as something thatshouldn’t be controversial.” In 2019, UAEM,
in conjunction with TranspariMED, publishedfirst report on clinical trials conducted by US
universities.
A key takeaway, Dasari noted, was thesignificant lack of transparency in academia,
even more so than at pharmaceuticalcompanies. After UAEM members discussed
the results with administrators at various
universities, Dasari said some of the worst
offenders became 100% compliant.
UAEM conducted a follow-up report in 2021,
which revealed that over half of the top 40
research universities were in violation oftransparency regulations. In the wake of thereport, Columbia University went from a 16.7%
compliance rate in 2019 to 100% in 2021. And
the number of institutions above an 80%
compliance rate increased from 16 to 36.
Dasari said FDA Commissioner Robert Califf
has highlighted the need for better compliance:“I think with him at the head of the FDA we’rereally excited to see greater enforcement.”
Dasari isn’t the only one who expressed her
dissatisfaction in writing. In January 2023, Frank
Pallone, ranking member of the House Energy& Commerce Committee, sent a six-page letter

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March 2023 

Navya Dasari

to the Food and Drug Administration (FDA) andNational Institutes of Health (NIH), criticizing
the organizations for not doing enough toenforce pharmaceutical companies’ disclosurecompliance on ClinicalTrials.gov. “FDA and NIH
both have a role in enforcement ofClinicalTrials.gov requirements,” the letter reads.
Making a Case for Clinical Trial Transparency
Bruckner, who founded the aforementioned
TranspariMED in 2017, is a vocal advocate forclinical trial transparency. He is also a partnerin Consilium Scientific, a nonprofit researchand educational organization dedicated to
informing and enacting health policy change inthe UK and around the world. “Failure to registerand fully report clinical trials harms patients,
wastes taxpayers’ money, and slows down thedevelopment of new treatments, vaccines andcures,” Bruckner said.

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The State of Global Clinical Trial Disclosure:
What Noncompliance Penalties Are in Place, and How They Are Enforced

He said one of his biggest accomplishments
is getting a lot more groups to understandthe problem and push for policy solutions. He
has brought together over 30 groups in overa dozen countries. He brought Transparency
International on board because it is “outside thenarrow medical scene; that’s sustainable.” Oneof his biggest challenges is capacity/bandwidth
to keep up with so many countries’ regulations.
Bruckner said the UK is the only country thathas addressed the transparency problem
since 1980. He cited the UK’s national clinical
trial strategy as “the gold standard,” cutting
unnecessary bureaucracy and paperwork.
“Countries should really look to the UK for a
way to solve this problem in a way that doesn’t
aggravate sponsors, the industry, in a way that’s
efficient…. Look to the UK model.” (See more on
UK regulations below.)

Till Bruckner

Figure 1: Potential Solution: UK Model

Trial Design
Ethics Approval
Trial Registration
Conduct of Trial
Results Reporting

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March 2023 

NationallyArchived
Health Research Authority
Automatic
Registration
Checks if
Results Reported

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The State of Global Clinical Trial Disclosure:
What Noncompliance Penalties Are in Place, and How They Are Enforced

CanadaIn 2019, the Canadian government createda new online portal to access clinical study
reports. However, according to a 2022 article
in Citeline’s In Vivo, the Canadian regulator
never passed regulations to build on a 2014 law
stating there is a duty to publicize clinical trial
information. New draft guidelines on registrationof trials and public disclosure of results werereleased in February 2023 and are out for public
consultation until April 24.

LATIN AMERICA
Argentina
According to the book Clinical Trials in Latin
America: Where Ethics and Business Clash(2014), in 85% of the protocols approved byexternal private research ethics committees(RECs), the Institutional Council for the Review
of Research Studies (CIREI) found a total of
92 infractions of The National Administrationof Drugs, Foods and Medical Devices
of Argentina’s (ANMAT’s) standards andregulations. For example, 42% of the protocols
did not state that results of the trial would
be made public and 24% did not assume
any obligation to participants following theconclusion of the study. Another study, focusedon clinical trial registration, suggested thatto increase compliance and promote clinical
trial registration, national health authorities,
sponsors, and local investigators could
implement a grassroots educational campaign
to improve clinical trial regulation.
MexicoMost industry-sponsored studies in Mexico
aim to comply with FDA regulations, while
national regulations are less strict compared tointernational standards. The agency responsible
for regulation in Mexico is the Federal
Commission for the Protection against

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March 2023 

Sanitary Risks (COFEPRIS). In terms ofregistration, once an applicant has received anauthorization letter from COFEPRIS, registration
is mandatory and must be completed within fivebusiness days. Many trials are tracked on
ClinicalTrials.gov, where Mexico currently has
over 4,000 registered trials, many of which have
yet to report results.
According to the Clinical Trials in Latin America
book, “No specific provisions exist to assure
study participants that they will benefit from theresults of the clinical trial.”

THE UK
The timeframe for publishing summary results iswithin one year (six months for pediatric trials)of the end of trial, according to UK’s Medicinesand Healthcare products Regulatory Agency(MHRA). Where applicable, it advises sponsors
to publish summary results within this timeframein the public register(s) where the trial isregistered.
The UK government will introduce a legal
requirement to make public the results of
all clinical trials within 12 months of trial
completion. Any company or university breaking
the law will be refused permission to start new
trials, the UK drug regulator announced on
March 21.
Sponsors do not need to submit the summary
report to the MHRA, but must confirm via email
once the result-related information has been
uploaded to the public register. If a clinical trial
is not on a public register or the results will not
be published in the register (for example, an
adult Phase I study), summary results should
be submitted via MHRA Submissions. Sponsors
should also submit a final report to the Research
Ethics Committee within the same timeframe

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The State of Global Clinical Trial Disclosure:
What Noncompliance Penalties Are in Place, and How They Are Enforced

for reporting the summary of results. Sponsorsof trials conducted in UK already registered in
the EU Register are able to submit results toEudraCT.
A spokesperson for the UK’s Health Research
Authority said: “Transparency about what
research is going on, and what its findings are,is important for patients, service users andthe public. It builds trust and accountability,
acknowledges their contribution andencourages participation in research. Beingtransparent also avoids duplication of effort andenables findings to be used to develop new andbetter treatments for patients and service users.
“Our Make it Public campaign demonstrates
our commitment to support and encourage theresearch sector to be transparent and open.”

THE EUROPEAN UNION (EU)From July 2014 to Jan. 31, 2023, it was possible
to register a trial on EudraCT under the EU
Clinical Trials Directive. While results wererequired under the directive, there was no
enforcement mechanism and no penalties
could be imposed. Since Jan. 31, 2022, trials
posted on the Clinical Trials Information System(CTIS) under the EU Clinical Trials Regulation(mandatory for new trials since Jan. 31, 2023),
European Economic Area (EEA) member states
have the regulatory framework to impose
penalties, as described below.
The regulation enables significant improvements
concerning the public availability of information
on clinical trials conducted in the EU/EEA,
including summary of results, via the public
CTIS website. Article 37(4) of the regulation
provides a clear legal obligation to post clinical
trial results, together with a plain language
summary of the results, within one year from theend of the clinical trial. It allows member states
to impose penalties applicable to infringementsof the Regulation (Article 94), and to take all
9March 2023 

measures necessary to ensure that they are
implemented. In January 2023, Pink Sheetreported that the EMA is working on restarting
this landmark policy on publishing clinical trial
data, with the first phase expected to start thisyear.
The EMA notes that it is important to makethe distinction between the disclosure rules
which have been applying in the context of theEudraCT website (and its public interface, theClinical Trials Register), and those which apply
now since the implementation of the Clinical
Trial Regulation and the launch of the CTIS,
which became mandatory for submissions as ofJan. 31, 2023.
In a prepared response, the EMA said: “[T]ogether with the European Commission andthe member states, [the EMA is] aware that
there is still work to be done to improve thesituation and have taken a number of actions tofurther improve the reporting rate of summaryof results in the Clinical Trial Register. Since
September 2018, EMA has been regularly
identifying trials with missing due results. EMA,
together with the European Commission and themember states, have been working on a numberof actions to further improve the reporting
rate in the EU Clinical Trials Register. EMA has
substantially improved the EudraCT website andits instructions in order to make results reportingeasier for academia and for commercial
sponsors.”
The EMA concluded with this statement:“Transparency is an essential component ofclinical research, and clinical trial information
and results need to be publicly available.”
Following the June 2019 issuing of a
joint letter reminding all sponsors of clinical
trials conducted in the European Union of their
obligation to make summaries of results ofconcluded trials publicly available, national
competent authorities (NCAs) and the EMA havesent reminders to noncompliant sponsors, toCopyright ©️ 2023 Pharma Intelligence UK Limited, a Citeline company (Unauthorized photocopying prohibited)

The State of Global Clinical Trial Disclosure:
What Noncompliance Penalties Are in Place, and How They Are Enforced

increase compliance with the transparency rules
and their follow-up on reporting obligations.
According to the EMA, due to these reminders,the percentage of posted results substantially
increased. However, for some trials thereminders were not successful: Many sponsors
could not be reached. A list of trials for whichsponsors could not be reached, or for whichsponsors did not follow up on the request of
results posting, is published on https://www.
clinicaltrialsregister.eu/.
The posting and publication of summary resultsin the EU Clinical Trials Register is further set
out in a European Commission guideline. The
publishing of results has been required since
July 2014. However, there is no legal basis for
EMA to impose penalties on sponsors who are
not fulfilling the legal requirements to provide

results in EudraCT. According to section 4.7(noncompliance, factual inaccuracy) on postingand publication of result-related information
on clinical trials, it is the responsibility ofthe member states to verify that, for clinical
trials authorized by them, the result-related
information is posted to the agency andtherefore to decide on further actions.
A study published in January 2023, “Towards
full clinical trial registration and results
publication: longitudinal meta-research study
in Northwestern and Central Switzerland,”found that approximately 10% of clinical
trials remained unregistered despite the legal
obligations. “More support for investigators andstricter enforcement by regulators are needed
to improve the transparency of investigatorsponsored trials in particular.”Figure 2: Number of Missing Trial Results
Single-country trials approved up to 2016 only, estimate
Italy

1299

Netherlands

849

Spain

837

France736

Sweden359

All others279

Denmark

273

Finland248

Germany

237

Belgium

221

Norway77

Austria74

December 2020

July 2020

Source: TranspariMED

10March 2023 

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The State of Global Clinical Trial Disclosure:
What Noncompliance Penalties Are in Place, and How They Are Enforced

National medicines regulators in Europe havefailed to ensure the publication of at least 5,488
clinical trial results, the report states. On a morepositive note, the star performer was Austria,
which increased its reporting rate from 26% to

65% within less than two years. Germany andAustria also achieved high reporting rates,
and Denmark and Belgium made substantial
progress.

Figure 3: Percentage of Trials with Results
Single-country trials approved up to 2015 only
64

UK*
44

Germany65

21

Denmark

47

25

Belgium
Spain

19

Sweden19

Finland

18

France

17

Italy

17
10

Netherlands
Norway66

26Austria

6

74

47
31
28

27
25
24

19

2020
Baseline

2022
Baseline

17% with results December 2020

% with results July 2020

Source: TranspariMED

A September 2022 report, the first of its kind,published by TranspariMED, Consilium Scientificand other and other European health groups,
found gaps in clinical trial disclosure regulations
across Europe.
Key findings of the report include:•	Regulators in at least five countries — Austria,
Belgium and Denmark — are actively
prompting trial sponsors to make the results of
their past drug trials public.

11

March 2023 •	Regulators in four countries — France, Italy,
Spain and Sweden — appear to be taking
little or no action on missing drug trial results.
In January 2023, Italy released its Registerof Observational Studies (RSO); registration
is mandatory for new requests submitted for
Ethics Committee review, and results are due
within 12 months of study completion. Legalbasis for the RSO is Article 6 of the Ministerial
Decree of Nov. 30, 2021.

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The State of Global Clinical Trial Disclosure:
What Noncompliance Penalties Are in Place, and How They Are Enforced•	None of the countries covered have laws
requiring the publication of clinical trial
results that do not involve investigative drugs
or medical devices. Legislation for Austria,

Germany and Sweden is unclear whether
regulations apply specifically to results
reporting.

EU member states that impose fines for failing to report the results of a drug trial*:
Country

Fines

Austria€25,000 - €50,000

Belgium€550 - €250,000

Denmark

To be determined

FinlandTo be determined

Germany€25,000 maximum

Netherlands€33,500

SwedenTo be determined*Updated to reflect current fines.

A month later, TranspariMED published anotherreport on compliance in the EU. The report
showed that the majority of unreported drug
trial results in Europe were concentrated withinjust four countries: Italy, the Netherlands,
Spain and France.

from participating in clinical trials for three to
10 years. It’s important to note that this law
applies only to trials for drugs, not medical
devices, and only covers drug trials registeredon the new EU-CTIS trial registry since January
2022.

TranspariMED’s Bruckner commented: “We areseeing a clear willingness by many national
regulators within the European Union to impose
sanctions if clinical trial sponsors fail to comply
with legal CTIS results reporting requirements. I
think many regulators’ patience has run out.”

An August 2021 notice from the Federal Agency
for Medicines and Health Products callingfor sponsors to publish clinical trial results
begins: “The FAMHP reminds all sponsors they
are obligated to publish the results of theirclinical trials in the European Clinical Trials
Database (EudraCT) within one year after theend of trial date (or six months for a paediatrictrial). Publication on external sources or thetransmission of reports to national competentauthorities is not sufficient. The guideline
applies retrospectively. Results should be posted
in the EudraCT database as soon as possible….”
In terms of enforcement, the letter only states:“The FAMHP will contact all sponsors of clinical
trials that have been conducted and completed
in Belgium for which no results have been
uploaded in EudraCT.”

Belgium
Belgium was the first EU country to disclose
specific details about its penalties. As of
February 2022, the Federal Agency for
Medicines and Health Products (FAMHP)
has the authority to impose fines of €550
to €250,000 and a prison sentence of up to
two years for failure to report results. Repeat
offenders can face maximum penalties of a€500,000 fine and a three-year prison sentence.
What’s more, a judge can ban repeat offenders
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March 2023 

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The State of Global Clinical Trial Disclosure:
What Noncompliance Penalties Are in Place, and How They Are Enforced

If a violation is found, a determination will bemade by a GCP inspector of the FAMHP, who
may then prepare a pharmacovigilance (PV)document of determinations. This PV document,
together with the inspection report, will betransmitted to the violator and the FAMHP
official-lawyer (being the head of the Divisionof Legislation and Disputes). The official-lawyer
can then, in consultation with the inspection,
propose an amicable settlement to the offender
for a minimum €4,000, the minimum amount of
the fine multiplied by the applicable surcharges.

the results in alignment with CTIS requirements
are liable to a fine or imprisonment of up to fourmonths. Interpretation of Chapter 6 of the Act
on Clinical Trials indicates that the DKMA will
check for Article 37 of Regulation 536/2014 (tosubmit results to CTIS rather than EudraCT in
this context). The DKMA will send a reminder tononcompliant sponsors and then take further
steps if the results are not reported. The agency
cannot itself issue a fine or sentence sponsors
to imprisonment; it must go through the publicprosecutor.

The Czech Republic
The requirements for clinical trials of medical
products and everything related to them are
specified in the national legislation which,although not currently aligned to EU regulations,refers to the 2003 EU directive (Act on
Pharmaceuticals; Decrees). The Czech Republic’s
first national law, Pharmaceutical Act, No.
79/1997, was amended several times. In short,a study sponsor must submit a final report into
the EudraCT database (CTIS).

Estonia
The Estonian Medicines Agency is theregulatory body governing clinical trials in
Estonia. All trials in Estonia are run according
to the Medicinal Products Act. Chapter 5 of theact regulates clinical trials in humans, stating:“The sponsor must submit an Estonian summaryof the results of a clinical trial of a medicinal
product aimed at an ordinary user to the
database specified in Article 81 of Regulation(EU) No 536/2014 of the European Parliamentand of the Council in accordance with Article
37(4) of the same Regulation.”

The Act on Pharmaceuticals also lists
misdemeanors and sanctions fornoncompliance. Sanctions could be imposedby the Legal Department of SÚKL, the State
Institute for Drug Control. For enforcement,
officials rely on GCP inspections. However, GCP
inspections typically only focus on the conductof the trial; it is unclear whether this would
include clinical trial disclosure.
Denmark
In October 2020, the Danish Medicines Agency(DKMA) announced it was taking tougher action
to ensure the publication of clinical trial results.
It cited a 2019 survey showing that only 23.6%of the non-commercial sponsors in Denmark
fulfilled their obligation to publish the resultsfrom clinical trials of medicines.
Sponsors are responsible for sending clinical trial
results to EudraCT. Sponsors who fail to publish

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March 2023 

Estonia goes into great detail regarding
various types of noncompliance. The sanction
for noncompliance with the requirements of aclinical trial of a medicinal product, including
provisions governing the submission of dataor the safety of a trial subject, is a fine of up
to 300 fine units. According to the European
Commission, one fine unit equals €4, for a total
fine up to €1,200. The sanction for the same act
committed by a legal person is a fine of up to€32,000.
FinlandIn Finland, no penalties have been establishedin legislation for noncompliance of clinical trial
results reporting, neither under the Clinical
Trial Directive 2001/20/EC or Clinical Trials
Regulation No 536/2014.

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The State of Global Clinical Trial Disclosure:
What Noncompliance Penalties Are in Place, and How They Are Enforced

SwedenAccording to Article 67b of Sweden’s Federal
Act on Medicinal Products and Medical Devices,
the Federal Council may, taking into accountinternationally recognized regulations, require
publication of clinical trial results.
Chapter 14 section 3, referring to EU pediatricregulation and EU directives, and chapter
16 section 1 of the Medicinal Products Act(2015:315) (läkemedelslagen) provide thelegal foundation for the Swedish Medical
Products Agency (MPA) to issue injunctions andprohibitions necessary for compliance with the
EU-CTR in relation to clinical trials. Although thelegislation does not specify clinical trial results,
decisions on injunctions or prohibitions may be
accompanied by a fine, the amount determined
per the Act on fines (viteslagen).

ASIA-PACIFIC
China
The Chinese Clinical Trial Registry (ChiCTR) is
a WHO International Clinical Trials Registry
Platform (ICTRP) primary registry. As per its
guidelines, after the completion of a trial,
the statistical results should be uploaded to
ResMan, a public management platform forclinical trials, and the results should be published
one year later.
Additionally, as per the Provisions for Drug
Registration (SAMR Order No. 28) (managed
by Drug Evaluation Center of China, NMPA),
trial registration is required. The provisions
were promulgated by the State Administration
for Market Regulation (SAMR) and officially
implemented July 1, 2020:“The sponsor shall register the drug clinical
trial protocol and other information on the
drug clinical trial registration and information
disclosure platform before carrying out the
drug clinical trial. During the drug clinical

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March 2023 

trial, the sponsor should continuously update
the registration information, and register the
drug clinical trial results and other information
after the drug clinical trial is completed. The
registration information is publicized on theplatform, and the sponsor is responsible for theauthenticity of the drug clinical trial registration
information.”
Sponsors found in violation of the following
shall be ordered to make corrections within a
specified time limit. Failure to do so shall resultin a fine of not less than 10,000 yuan but not
more than 30,000 yuan:
1.	Failure to register on the chictr.org.cn
platform as required before conducting drug
clinical trials;
2.	Failure to submit a safety update reportduring research and development as
required;
3.	Information such as clinical trial results are
not registered after the drug clinical trials arecompleted.
Hong Kong
Under Regulation 36B of the Pharmacy andPoisons Regulations (Cap. 138A), a Certificate
for Clinical trial/medicinal test (the certificate)is required for the purpose of conducting aclinical trial on human beings. The certificate
application must include a copy of the
protocol. Anyone violating this regulation isliable to a fine. The regulation only applies topharmaceutical products. The regulation does
not address disclosure of results.
India
A 2018 study, “Trial publication after registrationin Clinical Trials Registry of India (CTRI):
A cross-sectional analysis of randomized
controlled trials,” is revealing about the lack oftransparency in clinical trials in India. The study
was conducted by the Campbell Collaboration,
an international social science research network,and three other entities. It looked at trials from
June 2009 to June 2015.

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The State of Global Clinical Trial Disclosure:
What Noncompliance Penalties Are in Place, and How They Are Enforced

The study found that none of the trial details
were fully complete as per WHO criteria. Out of
2,938 trials, publication details of 78 (2.6%) werementioned in the Clinical Trials Registry - India(CTRI). From publication details of 676 trials, theaverage time to publication was 21.13 months.
Sources of monetary support and government
funding were found to be significant towards
influencing publication status.
Prospective registration on CTRI is mandatory
per the “New Drugs and Clinical Trials Rules,”although results posting is not mentioned.
Wording from the Central Drugs Standard
Control Organisation (CDSCO) indicates that
“Failure to comply with any provision of the Act
may result in one or more of following actions: i)written warning issued; ii) rejection of the resultsof the clinical trial; iii) suspension or cancellationof permissions; iv) barring of the investigator orsponsor from future clinical research, for such
period as considered appropriate by the DCGI[Drugs Controller General of India].”

designated publicly as dishonest disclosurecompanies and could be penalized such as
paying fines. Such firms have the opportunity to
discuss their positions during the process.
Kospi-listed firms, however, do not appear
to have separate disclosure guidelines forbiopharma companies.
Singapore
As with many countries, the regulatory
obligations for sponsors are vague. The
government does, however, state that it
establishes and maintains arrangements toensure compliance with the principles of GCP.
ICH guidelines regarding final reports read:“Upon completion of the trial, the investigator,
where applicable, should inform the institution;
the investigator/institution should provide
the [Institutional Review Board] IRB/IEC
with a summary of the trial’s outcome, andthe regulatory authority(ies) with any reports
required.”Japan
The Japan Registry of Clinical Trials (jRCT) is a
WHO ICTRP primary registry, funded by Ministryof Health, Labour and Welfare, while the Japan
Medical Association, Center for Clinical Trials(JMACCT), Japan Pharmaceutical Information
Center (JAPIC), and University Hospital Medical
Information Network (UMIN) are the partner
registries. According to PFSB/ELD Notification
No. 0831-9, a trial should be registered before
the first subject is enrolled, and the results
should be registered within one year after thecompletion of the clinical trial, unless it conflicts
with the laws and regulations of other countries
or if it interferes with publication in peerreviewed medical journals.

Very specific penalties are defined for lack of
notification of trial status to the authorities. A
person contravening Regulation 12 is consideredguilty of an offense and is liable on conviction toa fine not exceeding $5,000 or to imprisonment
for a term not exceeding two years or to both.
However, this does not appear to extend to the
public registry.

Korea
In Korea, pharmaceutical and biotech
companies listed on the Korea Securities
Dealers Association (KOSDAQ) index can be
penalized if they do not properly disclose major
information on clinical trials. They will be first

Costa Rica
In Costa Rica, the governmental bodies setting
regulations are the “Ley General de Salud”(General Law of Health), and the “Ley Orgánica
del Ministerio de Salud” (Organic Law of the
Ministry of Health). While the regulation does

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CENTRAL AMERICA
Central America has a common regulation called“Reglamento Técnico Centroamericano - RTCA”(Central American Technical Regulation). These
rules vary depending on the type of product.

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The State of Global Clinical Trial Disclosure:
What Noncompliance Penalties Are in Place, and How They Are Enforced

not appear to directly address the responsibility
for disclosure, it does outline research
participants’ right to information, including:•	Access to the results of their analyses, when
they have not undergone anonymization
processes, if the study design allows it•	To be informed about the progress, theunexpected adverse events and overall resultsof the research•	All verbal and written information is provided
in an understandable lexicon and in thelanguage of the participants.
Costa Rica maintains a national registerof trials conducted in the country, but it is
not considered a registry from a disclosure
standpoint.
GuatemalaHere, disclosure regulations fall under the
General Directorate of Regulation, Surveillance
and Control of Health through the Departmentof Regulation and Control of Pharmaceuticaland Related Products. The office provided thefollowing statement regarding Article 15 of the
Law on Access to Public Information: “Use anddissemination of information. The interested
parties will have criminal and civil responsibility
for the use, management or dissemination of
public information to which they have access, inaccordance with this law and other applicablelaws.”
Clinical trial regulations suggest that a summaryof results must be available to citizens throughthe agency website, but no specific regulatory
language supports this.

SOUTH AMERICA
Colombia
The National Institute for Food and Drug
Surveillance (INVIMA, Colombia’s regulatory
agency) manages different regulatory
processes related to clinical trials. From the

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March 2023 

evaluation of the initial protocol proposal to theassessment of protocol amendments, followup of administrative changes, surveillance andcontrol of the execution of trials at the approved
sites, etc., all of these procedures have different
timelines.
According to an INVIMA statement, “it isevery stakeholder’s responsibility to ensure
strict compliance.” The monitoring complianceof clinical trials is guided by international
standards, such as ICH, Colombian legal rules orregulations: Resolution 2378 of 2008, Resolution
8430 of 1993, and internal guidelines, among
others.
No specific language pertains to disclosure
other than a broad statement defining that
results should be relayed to the scientificcommunity.

OCEANIA
Australia
The Australian clinical trial requirements are
longstanding, with the ICH GCP Guidelinesfor Good Clinical Research Practice (GCRP)
in Australia first adopted in 1991. Clinical
trials are regulated at a number of levels
under Commonwealth and state and territory
legislation in Australia. The Therapeutic Goods
Administration’s (TGA’s) role in clinical trials is
to regulate access to “unapproved” therapeutic
goods (medicines, medical devices andbiologicals) for use in clinical trials through theClinical Trial Notification (CTN) and Clinical Trial
Approval (CTA) schemes.
Under the CTN scheme, trial proposals are
submitted directly to the reviewing Human
Research Ethics Committee/s (HRECs), whichassume the primary responsibility for ethicaland scientific review and approval. The CTA
scheme involves TGA evaluation of scientific
data for higher-risk trials in addition to the

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The State of Global Clinical Trial Disclosure:
What Noncompliance Penalties Are in Place, and How They Are Enforced

ethical review and approval by the responsible
HREC(s).
The legislation underpinning the CTN and
the CTA schemes requires that clinical trials
involving the use of “unapproved” therapeutic
goods be conducted in accordance with the
GCP guidelines, the National Statement on
Ethical Conduct in Human Research (National
Statement), and the protocol approved by
the applicable HREC. Trial sponsors arealso required to comply with other relevant

requirements of Commonwealth and/or state
and territory legislation. The Australian clinical
trial handbook provides further informationon conducting clinical trials in Australia using
unapproved therapeutic goods.
In regard to compliance management,
the TGA’s approach is outlined in the
Compliance management | Therapeutic
Goods Administration (TGA) and Complianceactions and outcomes | Therapeutic Goods
Administration (TGA).

High Compliance Risk

Figure 4: Tools Used to Address NoncomplianceCriminal
Prosecutions
Civil Penalties
Infringement Notices
Advertising Directions Notices

Low Compliance Risk

Injunctions
Enforceable Undertakings
Cancellations from ARTG
Suspensions from ARTG
Warning Letters
Education & GuidanceSource: Australian Therapeutic Goods Administration (TGA)

When a clinical trial is conducted in breach of
the conditions of the CTA scheme, the TGA has
power to revoke approval of the trial. The TGA
also has power, in specific circumstances, todirect that a clinical trial under the CTN scheme

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not be conducted or be stopped. Continuationof a clinical trial after approval has been
revoked or in breach of the conditions of
the CTN scheme may amount to a criminal
offense or a civil contravention under section

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The State of Global Clinical Trial Disclosure:
What Noncompliance Penalties Are in Place, and How They Are Enforced

19B or 19D of the Therapeutic Goods Act 1989.
Section 21A of the act specifies the grounds forprosecuting offenses related to not complying
with conditions of registration or listing.
In relation to noncompliance identified in the
GCP Inspection Program, the TGA adopted apragmatic approach with its Corrective andPreventative Action Plan (CAPA). This allows thesites to amend their processes, procedures andsystems, facilitating development of compliancestrategy aligned with relevant legislation andguidelines.
•	First, the TGA provides education and advice
to the responsible entity.
•	Next, a warning letter may be issued,
identifying the noncompliance, what corrective
action is needed, what other action the TGA
may take if the noncompliance is not remedied
within the specified timeframe, and education
on how to remain compliant in the future.
•	Civil penalties, if imposed, are 5,000 penalty
units for an individual, or 50,000 penalty units
for a corporation. A penalty unit is currently$275 for offenses committed on or afterJan. 1, 2023.
•	Criminal penalties, if warranted, can include
5–7 years’ imprisonment and fines of up to
4,000 penalty units.
It should be noted that the above guidancerefers to clinical trial authorizations and18

March 2023 

conduct, not to trial registration in a publicly
accessible register. However, the National
Statement on Ethical Conduct in Human
Research (and Australian Code for the
Responsible Conduct of Research) encouragesponsors to register on a publicly accessible
register and publicly disseminate results.
New ZealandMedsafe is New Zealand’s Medicines andMedical Devices Safety Authority, operating
under the Ministry of Health. Under the
Medicines Act of 1981, sponsors should submit
routine progress reports to Medsafe online, withthe first report sent not more than six months
after the trial’s approval date. Subsequent
reports should be submitted at six-monthintervals throughout the duration of the trial.
At the global end of the trial, a synopsis of
the final report should be sent to Medsafe
when available. While the penalties for specificviolations were unclear, the law states: “Every
person who commits an offense against theseregulations is liable on conviction to a fine notexceeding $500.”
As per Australia, there is no legal mandate
for clinical trial registration/results disclosure.
However, the National Ethics Standards statethat sponsors must register their clinical trials
in a WHO-approved clinical trial registry prior
to study start and must provide results in the
public database of the registry.

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The State of Global Clinical Trial Disclosure:
What Noncompliance Penalties Are in Place, and How They Are Enforced

In Conclusion
Nick Ide, formerly with ClinicalTrials.gov, shared
his predictions for the future of clinical trial
disclosure in the US:•	There will be more public scrutiny of content.
•	The FDA might focus not just on whether
studies were submitted, but the quality of thedata.
•	Standardization and better structure foroutcome measures.
•	Reaching agreement on key elements ofeligibility criteria and how to specify them.
Interpretation of penalties as defined inlegislation is difficult. In many cases, it isunclear whether regulations strictly apply todisclosure activities (registration in a publicly

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March 2023 

accessible registry and results dissemination)or more specifically to the direct interaction
with authorities and clinical trial authorization
requirements, which are often distinct processes.
While there has been movement toward
greater enforcement of clinical trial reporting
regulations across the globe, it is obvious that
more needs to be done. Management of clinical
trial disclosure is a complicated endeavor,
and regulatory agencies should take steps tomake compliance as easy as possible — andto enforce strict penalties for noncompliance.
Doing so will protect clinical trial participants
and, ultimately, the patients who rely on theselife-saving treatments.

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