How To Read A Protocol

In service training

Focus on Phase 1

Version 01 July 2013

Objective
At the completion of in service training, CPU
research professionals will:
 Defining a protocol and regulatory tie in
 Have an understanding about protocol specific language
 Be able to identify screening requirements
 Be able to identify study procedures
 Gain an understanding on how to create a study specific activity
schedule
 Gain an understanding of how to identify safety aspects including
obtaining Advise Experiences
What is a Protocol?? (and regulatory tie
in)

A protocol is Precise and detailed plans

for the study of a medical or biomedical
problem and/or plans for a regimen of
therapy.
 21 CFR 312 Sec. 312.23 IND content and format;
Pgh 6 requires a protocol to be submitted for each
planned study
 Both FDA E-6, and ICH E-6 guidelines require that
clinical trials be scientifically sound, and
described in a clear, detailed protocol.
 A trial should be conducted in compliance with
the protocol that has received prior institutional
review board (IRB)approval
What is a Protocol?? (21 CFR 312.23)

 Phase 1 Protocol:
 may be less detailed and more flexible than
protocols for Phase 2 and 3 studies.
 should be directed primarily at providing an
outline of the investigation
 an estimate of the number of patients to be
involved
 a description of safety exclusions
 a description of the dosing plan including
duration, dose, or method to be used in
determining dose--and should specify in detail
only those elements of the study that are critical
to safety, such as monitoring of vital signs and
Dosing time and interval
General Information
 Protocols rarely give a dose day or time - this is
determined by CPU management (PM; AD; Dir; PI)
• Does give a list of time points that are intended to
anchor off of the dose time
 Rarely give a dose interval (how much time
between subjects) but sometimes do

Subject Dose Blood Draw

1 8:00 9:00
2 8:05 9:05
3 8:10 9:10
 Zero hour and “Day” defined
General Information
 Zero Hour: A time when a subject is dosed

Monday Tuesday

Midnight 0 hour 8AM Midnight 24 hour 8AM 48 hour 8AM

Subject is
dosed

Day 1 Day 2
 Using a “Window” for procedures
Time point
8AM

Earliest Latest
7:30AM With in 30 minutes of scheduled time
8:30 AM

Earliest Latest
7:35 AM 8:25 AM
Almost never use the whole allowable +/- time to avoid mistakes

Blood Draw
done at 8AM

VS and ECG must be This half of window

done in window prior can not be used

SOP order of operations requirement for vitals signs and ECGs to be

conducted prior to blood draw further reduces available window
The plain language used in a
Protocol counts!
Screening window
 “…within 21 days of receiving first dose of test
material...”
 “21 days prior to being admitted to the study…”
 “Screening days -14 to -1….”
 “Study consists of a screening visit (Visit 1)……”
 “All screening procedures must be complete
within 14 days of (dose administration)
(admission)….”
The plain language used in a
Protocol counts!
Meals
 “Consumed over approximately a 30 minute
period”
 “Lunch will be administered 4.5 hours after the
breakfast meal….”
 “Lunch will be administered approximately 4.5
hours after the breakfast meal….”
The plain language used in a
Protocol counts!
Blood Samples
 “Pre-dose (within 30 minutes of dosing)”
 “…30 minutes prior to dosing”
 “…approximately 30 minutes before
administering the investigational product”
The plain language used in a
Protocol counts!
Return visits
 “..will be seen the morning of Day 3, Day 5 and
Day 8.”
 “..will perform designated procedures and 48 and
72 hour PK sample collections as out patient
visits..”
 “…48 hour vital sign, ECG and PK collection will
be conducted on an outpatient visit schedule….”
Common mistake – what is the
difference?
 “Final return visit between day 8 and 15 …”
 “Return between 8 and 15 days after the last
The plain language used in a
Protocol counts!
Common mistake – what is the
difference?
 “Final return visit between day 8 and 15 …”
 “Return between 8 and 15 days after the last
dosing…”
Oct 1 Oct 2 Oct Oct 4 Oct 5 Oct Oct 7 Oct Oct 9
3 6 8
Dose Day 2 Day Day 4 Day 5 Day Day 7 Day
(Day 1) 3 6 8

Dose 1 2 3 4 5 6 7 8
Day Days Days Days Days Days Days Days
after after after after after after after after
The plain language used in a
Protocol counts!
Vital Signs
 “…after 10 min of rest..”
 ..after at least 10 min of rest…”
The plain language used in a
Protocol counts!
What’s wrong with this wording???

 Period1 = Day -1 to Day 21

 Period 2 = Day 21 to Day 42
 Period 3 = Day 42 to Day 63
The plain language used in a
Protocol counts!
What’s wrong with this wording???
 Period1 = Day -1 to Day 21
 Period 2 = Day 21 to Day 42
 Period 3 = Day 42 to Day 63

What study period is Day 21 in? How about Day 42?

Determine how long a procedure
will take

8 subjects – 5 minutes apart

1 2 3 4 5 6 7 8

8:00 8:05 8:10 8:15 8:20 8:25 8:30 8:35

35 minutes (not 40)

Protocol Review
The slides are a guide.

They will tell you to read a section, or

find something in a source document,
or write something down.

The reading and activity is done at your

own self pace.

Once you have completed the

instructions given on the slide, advance
to the next slide.

That slide will review what you have read,

highlight and expound on specific points, or
present the answer or solution to what you
were asked to do.
Protocol Review

Top of page
“description of the study”

Middle of page
Administrative Information
Page 2

Top of page
“description of the study”

Original Signatures of those

involved in writing protocol

Investigator’s
signature not
necessarily
required
Page 3, 4 and 5
Page 3

Top of page
“description of the study”

Repeat of information from title page

learn objective of the study

Study drug content; oral dose; in both
fasted and fed states.

Screening window and “lab repeat”

information
 Bottom of Page 3 and Page 4

Note how this study is designed

Day -1 Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7

Period 1

Admit Dose CheckReturn Return Return Return Return

out The
variables
14 day wash out
have no
affect on any
Day -1 Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7 thing we do
operationally
Period 2

Admit Dose Check Return Return Return Return Return

out

There are two separate

days labeled Day 1
Page 3, 4 and 5
Page 6-9
Page 10 and 11
Page 12-13
Page 12-13
Page 15
Page 16 and 17
Page 16 and 17
Page 18 and 19
Page 22
Page 22
Page 23
Page 23
Page 24-27
Screening Source Document
Page 13 and 14
Protocol page 24
Screening Source Page 13
Protocol page 25
Screening Source page 14
Protocol page 27
Protocol page 28 and 29
Protocol page 28 and 29
Protocol page 31 and 32
Protocol page 31 and 32
Protocol page 31 and 32
Protocol page 31 and 32
Protocol page 31 and 32
Protocol page 31 and 32
Foot Note (4) is
listed after Vital
Signs
Protocol page 31 and 32
Procedure Time Point
Protocol page 31 and 32
Protocol page 31 and 32
Protocol page 31 and 32
Create SOE
Subject numbers
Protocol page 31 and 32
Protocol page 31 and 32
Protocol page 31 and 32
Create SOE
Protocol page 31 and 32
Create SOE
Protocol page 31 and 32
Protocol page 31 and 32
Protocol page 31 and 32
Protocol page 31 and 32

PK sample Pre-Dose line 4 PK sample 8 hour line

30
PK sample .25 line 8 PK sample 10 hour
line 32
PK sample .5 line 9 PK sample 12 hour
line 35
PK sample 1hour line 10 PK sample 16 hour
line 36
PK sample 1.5 line 11 PK sample 24 hour
line next PK sample 2 hour line14 page line
4
PK sample 3 hour line 15
PK sample 4 hour line 18
Protocol page 31 and 32
Create SOE
Protocol page 31 and 32
Create SOE
Protocol page 33
Screening
Protocol page 33
Screening

Match procedure
to source
Protocol page 33
Screening

Match procedure
to source
Protocol page 33
Screening
Protocol page 33
Screening
Protocol page 33
Screening
Protocol page 34
Protocol page 34
Protocol page 34
Protocol page 37 and 38
Protocol page 37 and 38
Protocol page 43
Protocol page 43
Protocol page 55
Wrap up
 Read the Synopsys
 Review the foot notes on the schedule of
procedures
 Follow the protocol exactly
 Understand the language
 Don’t read into everything so much that you
make more confusion than help; the PMs spend a
lot of time on SOEs, follow them!
Additional Exercise
 You have an additional protocol synopsis; event
table, and blank SOE
 If you wish, you can practice completing an SOE
using these hand outs
 Assume an 8AM first dose, and a 2 minute
interval
 Not required, as this training is already quite
lengthy.
Conclusion

No one who has sat through this crucible

of an in service should ever say “I don’t
know what is going on in the study”