How to Conduct Industry Sponsored Trials_Dr Mastura

7/27/2019 How to Conduct Industry Sponsored Trials_Dr Mastura

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Dr Mastura Ismail

Consultant Family Medicine SpecialistKlinik Kesihatan Seremban 2

Ministry of Health

Malaysia


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Did you know that allmedical drugs,treatments, preventions

and even medicaldevices have to gothrough a thoroughprocess before they are

available to you?

This process is call aClinical Trial.


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A term use to define the entire process ofbringing a new drug/device into the market

It includes: drug discovery

Product development

Pre-clinical research (microorganism/animal)

Clinical trials on human


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A properly planned and executed clinical trial

is a powerful experimental technique for

assessing the effectiveness of anintervention


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What is an investigational product?

A pharmaceutical form of an active substance or

placebo being tested or used as a reference in a clinical

trial, including products already with a marketing

authorisation but used or assembled (formulated or

packaged) in a way different from the authorised form,

or when used for an unauthorised indication, or when

used to gain further information about the authorised

form


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What makes Clinical Trial different from Standard of Care

Involves human subjects

Test an intervention be it a product, procedure or health caresystem.in order to improve standard of care!

Measures effects over a period of time

Most have a comparison CONTROL group

Must have method to measure intervention

this is captured in the protocol and this must be stuck to

meticulously if the question is to be answered!!

Focuses on unknowns: effect of intervention

Must be done before medication is part of standard of care

Standard of Care all about clinical judgement decision/flexibilitytrials need all to stick with the protocol, no deviation within your

clinical judgement


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You need to be trained in ICH Good Clinical Practice

Then you have to register yourself as investigator inthe National Medical Research & Register : indicateyour interest to your relevant research field

The Clinical Research Assistant will contact you

using the NMRR database, personal invitation orothers ways (FMSA )

CRA will send an email to invite your participation inthe clinical trials

The Site Information Form and Study Protocol will besent to you (you will have to sign a ConfidentialDisclosure Agreement prior to it )


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Basic Concepts

The protocol. Establishes the question what is the primary end

point.

Secondary objectives; a few related, appropriate secondary

questions are normal as long as they do not distract from the

primary.

Trial is then designed around these. The protocol sets out how

the question will be answered


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The protocol.all in the title

Single centre, placebo controlled etc etc

Who is conducting the trial, who is sponsoring it, where is it to

be conducted and on whom will you be conducting the research

What are you testing? Is it safe, have the tests been validated?

Why is this research needed.

What are the risks, what are the procedures, how will data becollected. How did you calculate how many patients you will

need.


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You have to answer questions after reading the studyprotocol

State : your interest to participate

Main site information: Principle Investigator (PI) , Sub-PIand Study Coordinator (SC)

Clinical trial experience

Patient recruitment based on the study protocol

Resources / Staff availability

Institutional Ethic Committee (IEC)/Institutional ReviewBoard (IRB)

Facilities and Logistics: clinical work place & equipments,blood processing facilities, investigators contract &agreement , study monitoring

Training needs of the study team (ICH GCP and data entry)


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Phone interview Survey study centre: Site visit confirmation

letter

Local Signatures

Letter to FDA (using clinic letter head)

Shippers declaration application (human

sample transportation letter) from relevantDistrict Health Office near the airport:specimen send lab outside the country


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CVs of PI, Sub-PI and study team

Approval from Head Department/ District HealthOfficer

Site selection visit follow-up letter

Sign Contract

Investigator s Meeting

Study begins once everything in-placed

Letter of Intent for Study Payment


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Informed Consent Form

As it says a form by which you gain informed consent

Few key requirements which must be included. Very difficult

balance many page forms. Still informed consent?

Special circumstances children and emergency. What about

this setting? When do you need a witness?

Whole point of GCP is to protect the rights of the subject


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The Case Record Form

Turns the protocol into your data capture system

Should only collect data listed in the protocol and nothing else

i.e unless you will use weight and have set out to do so, no

need to record. Often far too long and collects data that is not

used.

Differs from the source data - patient notes and lab reports.

This is a central concept in GCP that data is always verifiable

Data taken from here and entered into a database and then

exported to statistical package. Important to keep CRFs to allow

you to go back and resolve data queries


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Database and Statistics

Likely to need stats advice right at the start to help you decide

on the all important n. How will you randomise

Protocol needs to explain statistical objectives of your trial but it

is the report and analysis plan that sets out how you will analysis

the data. Must be finalised before database close to avoid risk ofmanipulating the data

Database should be secure and have an audit trial. Currently

difficult in non-commercial trials


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Keys to following the Protocol.The Case Record

Form, Source Data and SOPs.

Operations manuals or SOPs translate the protocol to

the practical and operational steps appropriate to your

site


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Who is involved? : Need to identify your team

Investigators

Coordinators / Project managers

Nurses, clinical officers, fieldworkers

Pharmacists

Data manager and entry clerks Monitor

Laboratory staff

And possibly.

Data safety and monitoring board

Clinical trial steering committee


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Why did we need recognised internationalguidelines for conducting trials?

Following famous cases such as the Nazis in WWII and black American men insyphilis studies (19321972) there followed the declaration of Helsinki

Agreement between countries that there needed to be a global standard bywhich all trial are conducted

This is Good Clinical Practiceprotects those in a trial, but also those whostreatment will depend on the data

Essentially ensures that the rights of the patient are protected and by all thosegiven a drug or intervention in the future based upon that data


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a standard for the design, conduct,performance, monitoring, auditing, recording,analyses, and reporting of clinical trials thatprovides assurance that the data and

reported results are credible and accurate,and that the rights, integrity andconfidentiality of trial subjects areprotected. (ICH GCP)


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1. Good protocol -Weigh risks vs. benefits2. Obtain IRB/IEC approvals3. Protect the subjects

Obtain Informed Consent,

Ensure safety, rights & confidentiality4. Use qualified study team

5. Handle investigational products appropriately

6. Implement quality systems

7. Record and analyze information appropriately

8. Follow the protocol and trial SOPs!!!!


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Other things to think about

Clinical trial insurance / Non-negligent harm cover

Safety reporting

Ethics committee safety and annual updates

Clinical trial registries

Sponsor reports

Publication planning Logistics, transport, budgeting

Drug/vaccine storage

Sample transportation, export, storage

Data archiving SOPs, training records and equipment service contracts


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Too daunting, are you put off completely?

Dont be!

Excellent way to learn about researchplenty of help andplenty of funding out there

More money than ever going into capacity building for clinical

trials in resource limited settings

Many opportunities for training and further qualifications Great field of research - whatever your training. Getting an

answer to a trial could influence the way patients are managed

or make a new drug/vaccine available. The possibility for

improving health outcomes for thousands rather than one

patient in front of you


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Organization is key!

Manage your to do list effectively. This can be divided into two categories. Those that have to be done at a specific time

Those that are open-ended

Implement a system to keep track of names and telephone numbers, eitherelectronically or on a paper rolodex.

Create a filing system for your CRFs that works easily and consistently.

Remember, neat and organized are NOT the same thing!

Manage your time in meetings. If you are coordinating the meeting, always usean agenda, and stick to it!

Documents

How to Conduct Industry Sponsored Trials_Dr Mastura