White Paper

Clinical Trial Disclosure
Compliance a Moving Target Due toEver-changing Global Regulations

September 2023

Introduction

Maintaining clinical trial disclosure complianceis a challenge, whether a sponsor is conducting
five trials or 500 trials. For sponsors with trialsites in multiple countries, keeping up withconstantly changing global regulations makes
compliance even trickier. Let’s take a look atsome sobering statistics as well examples of thetypes of changes sponsors can expect.
Table 1. Top 10 countries/regions with changes/
updates Sept. 30, 2022 – May 9, 2023
Country/RegionChanges

Updates

EU1639InternationalRegistries

79UK

510US

312Japan

39Netherlands

34Ireland

33Italy22

Denmark

23New Zealand

12To date this year, 115 updates have been tracked
across global regulatory agencies. As a result,these changes necessitated 59 updates to theTrialScope Intelligence database. Additionalcountries with recent disclosure updates
include Australia, Bosnia, Canada, Germany,India, Latvia, Panama, Peru, Serbia, Slovakia,
Switzerland, and Thailand.

2September 2023 In the EU, until Regulation 536/2014 (EU CTR),requirements for clinical trial applications varied
according to the member states. The EU CTR
that replaced the clinical trials directive (EUCTD) in January 2023 required that Member
States revise their local legislation to beconsistent with the regulation.
The most common types of global disclosure
updates are new guidance documents,
newsletters — primarily the European
Medicines Agency (EMA) since the mandatory
implementation of the Clinical Trial Information
System (CTIS) portal — and authority news andnotifications.
Changes to disclosure regulations are nothing
new. In a 2020 recap, Thomas Wicks, Head ofTransparency Operations for Citeline, outlined
five significant developments, including US
Federal Drug Administration (FDA) guidanceon civil monetary penalties for disclosure
noncompliance and Japan requiring disclosureof protocol and trial results information on thejRCT registry. While the coronavirus pandemic
and Brexit precipitated many of the changes
that year, regulatory agencies continue to finetune their disclosure rules, much to the chagrinof the sponsors trying to keep up with them.
Given existing EMA and Health Canada datasharing requirements, sponsors may need toconsider how they will anonymize data collectedfrom devices like mobile phones and wearables.
This could lead to more targeted regulations
emerging in the future to provide guidancearound data capture through these types ofconsumer technologies.

Copyright ©️ 2023 Pharma Intelligence UK Limited, a Citeline company (Unauthorized photocopying prohibited)Clinical Trial Disclosure Compliance a Moving
Target Due to Ever-changing Global Regulations

The processes for implementing disclosure
rule changes varies widely. In the UK, forexample, the process for updating regulations
is consistent with government departments.
Smaller changes to regulations can be made by
the agency on behalf of the secretary of state.
Major updates to policy would need to be madein the form of a Statutory Instrument which islaid in Parliament.
In India, according to Shridhar Narayananof the India Pharmaceutical Alliance (IPA),an expert committee drafts regulations andguidelines, which are shared with all relevant
stakeholders for input. Once the changes are
made, they are announced on the Central
Drugs Standard Control Organization (CDSCO)
website. Official regulatory points of contactfrom each sponsor organization are also
notified via email. Sponsors’ regulatory
intelligence teams closely liaise with the CDSCO
office to understand any recent release of new
regulations or regulatory amendments, if any.

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September 2023 Copyright ©️ 2023 Pharma Intelligence UK Limited, a Citeline company (Unauthorized photocopying prohibited)Clinical Trial Disclosure Compliance a Moving
Target Due to Ever-changing Global Regulations

Regulatory focus: Japan
Japan has two laws relating to pharmaceuticals:
The Pharmaceuticals and Medical Devices Act,
which applies to commercial trials that includeproducts intended for marketing (“Chiken”trials); and the Clinical Trials Act, which applies
to non-commercial trials, including those fundedby manufacturer and unapproved/off-label
products.
According to the Ministry of Health, Labour andWelfare (MHLW), registration with the Japan
Registry of Clinical Trials (jRCT) is required when
conducting a clinical trial in Japan.
Clinical trial disclosure is stipulated in Article272-2 (in Japanese) of Japan’s Ministerial
Ordinance for Enforcement of the Act on
Securing Quality, Efficacy and Safety of
Pharmaceuticals and Medical Devices,
Regenerative and Cellular Therapy Products,Gene Therapy Products, and Cosmetics (PMDAct). While this act dates back to 1961, recent
development such as the advent of digital
healthcare have prompted further updates.
In January 2018, member companies of
the Japan Pharmaceutical Manufacturers
Association (JPMA), part of the International
Federation of Pharmaceutical Manufacturers &Associations (IFPMA), committed to clinical trial
data sharing based on the “IFPMA Principles for
Responsible Clinical Trial Data Sharing.”
Under the Clinical Trials Act (CTA) enactedin April 2018, a clinical trial plan must be4

September 2023 

submitted to the MHLW before the trial’s start.
It should be noted that the act applies only tointerventional studies, and not to prospective
or retrospective observational studies. The trial
plan must include World Health Organization(WHO) Registry Network specifications, detailsof participating sites ― such as principal
investigator (PI) and site contact information― along with CRB approval date and facility
details. In addition, the trial plan must be
uploaded to the Japan Registry of Clinical Trials(jRCT).
jRCT allows for the registration of all types ofclinical trials, including drugs, medical devices,and observational studies. Trials can beregistered on its platform in both Japanese andEnglish, and should be registered prospectively(i.e., prior to first participant consent). Protocoland results information for Phase I to IV trials
is made publicly available. A summary of thetrial results is required to be submitted within
one year of the clinical trial completion date for
specified clinical trials, in compliance with theCTA, or at least within one year after approval
or marketing for trials of commercial products.
In March 2023, the jRCT migrated registereddata from two registries ― the Japan Medical
Association Clinical Trial Registry System(JMACCT-CTR) and the Japan Pharmaceutical
Information Center Clinical Trial Information(JapicCTI) ― to the jRCT Clinical Research
Submission and Disclosure System.

Copyright ©️ 2023 Pharma Intelligence UK Limited, a Citeline company (Unauthorized photocopying prohibited)Clinical Trial Disclosure Compliance a Moving
Target Due to Ever-changing Global Regulations

Over the years, Japan has seen several changes in regulations related to clinical trials1:

Creation of several ethicalguidelines for clinical research
involving human subjects (2001-)

The ethical guidelines for epidemiological, clinical, and humangenome/analysis research were separately created

Committee on clinical researchagainst scandal of antihypertensive
drugs by MHLW (2013-2014)

The ethical guidelines were reviewed and thenecessity for a legal system was identified

Investigative committee on thesystems related to clinical researchby MHLW (2014)

The conclusion of committee was that
there was a need for legal regulations

Ethical Guidelines for Medical
Research Involving Human Subjects(December 2014)
The Ethical Guidelines for Clinical Researchand the Ethical Guidelines for EpidemiologicalResearch were merged

The Clinical Trials Act (April 2018)

Ethical Guidelines for Medical and Biological Research Involving Human Subjects(March 23, 2021)
Developed by merging the Ethical Guidelines for Human Genome/Analysis Research (2013) and the Ethical Guidelines for
Medical Research Involving Human Subjects (December 2014)

Source: MHLW: Ministry of Health, Labour and Welfare.

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September 2023 Copyright ©️ 2023 Pharma Intelligence UK Limited, a Citeline company (Unauthorized photocopying prohibited)Clinical Trial Disclosure Compliance a Moving
Target Due to Ever-changing Global Regulations

Putting it in perspective
Anthony Keyes is program administrator atJohns Hopkins University, where he, among
other duties, directs the ClinicalTrials.gov
Program. With all the regulatory changes
constantly coming down the pike and principal
investigators often managing disclosurecompliance, Keyes says, “We call it the WildWest.”
Keyes is co-chair of the Clinical Trials
Registration and Results Reporting Taskforce, anational consortium of members of academic
medical centers, universities, hospitals, andnonprofit organizations focused on theimplementation of domestic clinical trials
registration and results reporting requirementsin the ClinicalTrials.gov registry. The all-volunteer
task force has over 400 member sites, andKeyes says the Multi-Regional Clinical Trials

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September 2023 Center (MRCT) of Brigham and Women’s
Hospital and Harvard is “the backbone” of theorganization.
Stressing the importance of communication,
Keyes says, “Every time the federal government
comes out with a new policy… we will
advertise it through our task force and variousorganizations.”
While the task force focuses on US-based trials,
Keyes says that, as far as the global community
is concerned, the Drug Information Association(DIA) Disclosure Community is a reliable sourceof disclosure regulatory information. The group,
led by Francine Lane, Senior Director of ProductManagement at Citeline, is made up of DIA
members who are subject-matter experts andcollaborate to determine best practices.

Copyright ©️ 2023 Pharma Intelligence UK Limited, a Citeline company (Unauthorized photocopying prohibited)Clinical Trial Disclosure Compliance a Moving
Target Due to Ever-changing Global Regulations

Additional resources
ClinRegs, managed by the National Institutes ofHealth (NIH), is an online database of countryspecific clinical research regulatory information
designed to assist in planning and implementing
international clinical research. However,countries are included based on the National
Institute of Allergies and Infectious Diseases’(NIAID) international clinical research priorities,
which means the scope of coverage is limited.
The database features 23 countries, someof which are less strategically important(e.g., Liberia, Mali, Malawi) than those witha preponderance of clinical trial sites. For
example, EEA/EU countries and Japan, twoareas with important and complex disclosure
requirements, are omitted, and details for listedcountries are minimal. Recent alerts on social
media featured updates for Liberia, Zimbabwe,
Bangladesh, Thailand, and Vietnam.
Another NIH resource is the Hot Off the PRS!
e-newsletter, which provides timely updates
about the Protocol Registration and Results
System (PRS), a web-based tool used to submit
clinical study information to ClinicalTrials.gov.
Individuals can subscribe here. Keyes notesthat while a sponsor may have many trial sites

outside the US, if the trial itself is based in theUS, then the FDA is the governing body.
The EU circulates the Clinical Trials Highlights
e-newsletter, providing regular updates on CTIS,
the business change initiative Accelerating
Clinical Trials in the EU (ACT EU), and relatedtopics. Individuals can subscribe here.
As Keyes emphasizes, study sponsors must
hold themselves accountable for disclosurecompliance, While many sponsors may rely
on contract research organizations (CROs) tohandle disclosure, the proverbial buck stops
with those in charge of compliance. “We makeourselves the responsible party,” he says.
ClinRegs, the NIH Hot off the PRS!, andregulatory intelligence solutions focusedon clinical disclosure such as TrialScopeIntelligence, provide true global coverage with
continuously updated information about theregulations and registry requirements. For
more information on TrialScope Intelligence, arepository of knowledge necessary for global
clinical trial disclosure compliance, visit
Citeline.com.

References
1. Maeda H. The Current Status and Future Direction of Clinical Research in Japan From a Regulatory Perspective. Front Med (Lausanne). 2022 Jan
13;8:816921. doi: 10.3389/fmed.2021.816921. PMID: 35096908; PMCID: PMC8792780.

Citeline’s TrialScope Intelligence platform is an all-in-one disclosure regulatory intelligence solutionthat centralizes the critical knowledge needed for timely compliance with global clinical trialrequirements. Our experts monitor, collect, curate, and analyze all new and updated requirements.
Users are alerted of any changes and can communicate/collaborate with stakeholders.

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