Introduction to disclosures in clinical trials. This presentation provides brief information about types of disclosures, FDAAA (www.clinicaltrials.gov) and EU (EudraCT) portals for clinical trial protocols and result summary disclosures in public domain.

1. Dr. L. H. Hiranandani College
of Pharmacy, Ulhasnagar
and
Konkan Gyanpeeth Rahul Dharkar College
of Pharmacy and Research Institute, Karjat
in Collaboration with Association of
Pharmaceutical Teachers of India (APTI)
And
Indian Pharmaceutical Association (IPA),
organized
E-Faculty Development Programme
on
“Pharmaceutical Product Development:
Challenges and Opportunities.”
Date: 18 June 2020 Time 11:00 to 12:00
Dr. Rajendra Dhande
Ethics and
Disclosures in Clinical
Trials: An update

2. Agenda
• What is Disclosure?
• Need of Disclosures in CR
• Types of Disclosures in CR
• Evolution of Disclosure
• Mandate of Disclosure
• Regulatory Bodies and Regulations in Disclosures
• Elements of Disclosures in Registry
• Redacted Regulatory Documents
• Plain Language Summary
• Advantages and Disadvantages of Disclosures

3. What is Disclosure?
“The act of making
something known or
the fact that is
made known.”

4. What is Disclosure?

5. Need of Disclosures in CT
Positive results
Compliance
Adverse Events
Study Completion
Negative results
SAEs
Deaths
Subjects safety issues
Reasoning of Subjects
withdrawal
Non-compliance
Transparency in CT

6. • Reporting biases in the
published literature
• Research are inconsistently or
selectively reported
• Most of trials are not
published
• Published after considerable
time after study completion
Need of Disclosures in CT

7. Studies have also found that,
the trial results reported to
regulatory agencies differed
significantly, from the results
publicly reported in journals.
Need of Disclosures in CT

8. Need of Disclosure
• In 2006, a sponsor conducted a Phase 1 trial in healthy
volunteers that caused catastrophic systemic organ
failure resulted in all six trial subjects.
• A controversy emerged because a similar study had
been done in 1994 with similar outcomes.
• It was suggested that had the trial information been
available on a public registry, perhaps the second trial
would never have been conducted and patient safety
would have been protected.

9. Need of Disclosures in CT
• Reference to Researcher
• Helps patient to find appropriate indication study to
get enrolled.
• Information readily available in public domain
• Information related to participant safety from
previous experiences
• Can avoid repeating the similar mistakes to ensure
participants safety.

10. Types of Disclosures in CT
• Protocol Summary
• Result summary
• Plain Language summaries/Lay persons summary
• Redacted Regulatory Documents
• Financial Disclosures
• Manuscripts/ Publications in Scientific Journals

11. Media for Disclosure
• Clinical Trial Registry of specific regulatory
authority. Eg. CTRI, CT.gov, EudraCT…
• Clinical trial register of organization. eg. GSK,
Pfizer, Novartis, AstraZenica…
• Scientific journals eg. Journal of clinical trials
• Official data base portals eg. EU portal for Plain
Language summary

12. Evolution of Disclosure
• The Declaration of Helsinki represents the first
major initiative in the timeline of transparency.
• The Declaration was first adopted in 1964 and
has been amended 7 times.

13. • In 2000, www.clinicaltrials.gov was
implemented as a result of the Food and Drug
Administration Modernization Act of 1997
(FDAMA).
• The task was focused on CTs of investigational
new drugs in serious or life threatening diseases
• NIH and FDA collaboratively established a site
and was made available in Feb. 2000
Evolution of Disclosure

14. Evolution of Disclosure
• In September 2016, the United States Department of
Health and Human Services (HHS) amended Title VIII of
the Food and Drug Administration Amendments Act
(FDAAA) of 2007 as “Final Rule” .
• Trials that start on or after January 18, 2017 or with a
Primary Completion Date on or after January 18, 2017
are subject to the Final Rule requirements
• As of January 18, 2018, all provisions of the Final Rule
are in full effect

15. Evolution of Disclosure

16. • The Clinical Trials Registry- India (CTRI),
hosted at the ICMR's National Institute of
Medical Statistics (http://nims-icmr.nic.in)
• Launched on 20th July 2007.
• Initiated as a voluntary measure, since
15th June 2009, trial registration in the CTRI
has been made mandatory by the Drugs
Controller General (India) (DCGI)
Evolution of Disclosure

17. • The European Union (EU) Clinical Trials
Register https://www.clinicaltrialsregister.eu/ was
launched 23/03/2011.
• The information contained in the EU Clinical
Trials Register is extracted from
European Union Drug Regulating Authorities Cli
nical Trials (EudraCT0, the EU clinical trials
database.
• EudraCT is commenced in May 2004.
Evolution of Disclosure

18. • In 2005, the International Committee of Medical
Journal Editors (ICMJE) (a group that includes
many of the leading medical journals) instituted a
policy.
• Its member journals would only publish trials that
had been registered in a public trials registry at or
before the time of first patient enrollment.
Mandate of Disclosure

19. Mandate of Disclosure
• FDA Amended Act in 2007, Section 801
• Mandated registration and results posting for all
applicable clinical trials on a public database.
• Under the FDAAA, a non-Phase I clinical trial must
be registered if it has at least one site in the United
States or is investigating a drug, device, or biological
agent that is subject to FDA oversight.

20. Mandate of Disclosure
• As per FDAAA results must be reported within
twelve months of trial completion, and failure to
comply can result in a penalty of up to $10,000
per day.

21. CTR of Regulatory Bodies Across the
Globe
Country Clinical Trial Registry Link
United States ClinicalTrials.gov:*
https://www.clinicaltrials.gov/ct2/home
Canada Health Canada Clinical Trial Database:
http://www.hc-sc.gc.ca/dhp-
mps/prodpharma/databasdonclin/index-eng.php
European Union EU Clinical Trials Register:*
https://www.clinicaltrialsregister.eu/
Australia Australian New Zealand Clinical Trials Registry:*
http://www.anzctr.org.au/
China Chinese Clinical Trial Registry:*
http://www.chictr.org.cn/enIndex.aspx
India Clinical Trials Registry – India:*
http://ctri.nic.in/
Japan Japan Primary Registries Network:*
https://rctportal.niph.go.jp/

22. Elements of Disclosures in Registry
• As per WHO following 20 elements are required,
1. Primary Registry and Trial
Identifying Number
2. Date of Registration in Primary
Registry
3. Secondary Identifying Numbers
4. Source(s) of Monetary or Material
Support
5. Primary Sponsor
6. Secondary Sponsor(s)
7. Contact for Public Queries
8. Contact for Scientific Queries
9. Public Title
10. Scientific Title
11. Countries of Recruitment
12. Health Condition(s) or Problem(s)
Studied
13. Intervention(s)
14. Key Inclusion and Exclusion
Criteria
15. Study Type
16. Date of First Enrollment
17. Target Sample Size
18. Recruitment Status
19. Primary Outcome(s)
20. Key Secondary Outcomes

23. Elements of Disclosures in Registry
• Title: Pharmacokinetic, Safety, Tolerability,
and Clinical Effect of Topical Umeclidinium
in Primary Axillary Hyperhidrosis
• https://clinicaltrials.gov/ct2/show/study/NCT025
63899?term=202093&draw=2&rank=1

24. Redacted regulatory Documents
• Redacted regulatory documents which can be
used as disclosures are
• Clinical trial protocols
• Statistical analytical procedure
• Clinical study report

25. Redacted regulatory Documents
• These documents are processed to avoid disclosing
the personal information identification (PII)
• The PII includes names, direct addresses or any
other information which can directly or indirectly
relate to the specific person
• Eg. Name, street address, telephone numbers, subject
numbers,

26. Redacted Regulatory Documents

27. Plain Language summary
• There is a rule in Europe that clinical studies must
have a summary written in plain language.
• Summaries written in plain language help people
who are not scientists or doctors understand complex
medical information.
• People who participate in clinical studies, and others,
may want to know information about clinical study
results.

28. Plain Language summary
• Lay summaries are a way to share clinical study
results, but they do not replace other ways that
information is shared.
• Lay summary writers must think about how they can
help readers understand the information.
• The information should be provided in such a way
that a 6th grade student shall understand the context.

29. Advantages of Disclosures
• Clinical trial transparency
• Help in patient recruitment
• Registry helps patients get enrolled in the
relevant trials
• Quick and scientific reference to the researchers
• No repetition of trials with hazardous outcomes

30. Disadvantages of disclosure
• Data Confidentiality especially subject level data
• Increased exposure of information may be
closely linked to the process of patenting a
recently-discovered use of a known drug.

31. Thank you…