Clinical Trial Protocol Amendment Summary: Health Economics Focus

This assignment presents a clinical trial protocol amendment summary for a Phase III randomized controlled trial evaluating a new drug (Drug AB56) against standard chemotherapy for breast cancer. The summary details key modifications to the original protocol, driven by the principal investigator's identification of three essential changes. These include the addition of a secondary objective focused on health economics, incorporating cost-effectiveness analysis to compare the experimental and standard treatments. The protocol is also updated to include documentation of hospital admissions and emergency room visits for each participant to inform the economic evaluation. Furthermore, the amendment introduces CT scans of the abdomen and pelvis, along with bone scans, as part of the screening process to exclude patients with metastatic disease. Finally, the SF-36 quality of life questionnaire is to be completed at the end of the treatment. Each modification is accompanied by a rationale explaining the need for the change and its impact on the study's design and objectives. The document reflects adjustments to the protocol sections on objectives, trial design, eligibility criteria, intervention, and outcomes, as well as considerations for the informed consent form.

Running head: CLINICAL RESEARCH (TRIAL DESIGN) 1
Clinical Research (Trial Design)
Student’s Name
Protocol Number: PRP-125
Protocol Version: 1.0
Protocol Date: (Assignment Due Date)

CLINICAL RESEARCH (TRIAL DESIGN) 2
Clinical Research (Trial Design)
Section A: Description of Changes to Clinical Trial Protocol
Tittle of Protocol Section: Objectives (Secondary Objective)
Previous Text:
1. To evaluate safety and tolerability
2. To compare overall survival
3. To evaluate the associated quality of life
Revised Text:
1. To evaluate safety and tolerability
2. To compare overall survival
3. To evaluate the associated quality of life
4. To evaluate health economics
Rationale:
A secondary objective encompassing health economics has to be incorporated in the
protocol. The need of this economic evaluation is to quantify the comparative costs of the
standard care therapy and the experimental therapy. Cost effectiveness is a significant goal to be
incorporated in the protocol.
Tittle of Protocol Section: Trial Design
Previous Text:

CLINICAL RESEARCH (TRIAL DESIGN) 3
A multi-centre, phase III, randomized controlled trial evaluating the efficacy of Drug
AB56 to standard of care chemotherapy in patients presenting with breast cancer. A total of 250
eligible, consenting women with histogitically confirmed breast cancer will be randomized to
receive either study DrugAB56 or standard of care chemotherapy. Randomized patients will
receive treatment with DrugAB56 administered orally at the dose of 500mg daily for period of 3
months or receive standard of care chemotherapy administered intravenously every month (i.e
every thirty days) for 3 cycles for a period of 3 months. Once treatment is completed, study
participants will be assessed in clinic every 6 months and then annually for 5 years for disease
progression, toxicity, survival and quality of life.
Revised Text:
A multi-centre, phase III, randomized controlled trial evaluating the efficacy of Drug AB56 to
standard of care chemotherapy in patients presenting with breast cancer. A total of 250 eligible,
consenting women with histogitically confirmed breast cancer will be randomized to receive
either study DrugAB56 or standard of care chemotherapy. Randomized patients will receive
treatment with DrugAB56 administered orally at the dose of 500mg daily for period of 3 months
or receive standard of care chemotherapy administered intravenously every month (i.e every
thirty days) for 3 cycles for a period of 3 months. Once treatment is completed, quality of life
assessment shall be completed by study participants at the final treatment visit to assess the
quality of life at the end of the treatment. Also, study participants will be assessed in clinic every
6 months and then annually for 5 years for disease progression, toxicity, survival and quality of
life.
Rationale:

CLINICAL RESEARCH (TRIAL DESIGN) 4
Often, side effects of a treatment must be examined in any randomized control trial. Such
adverse effected can be obtained through comparative analysis of the control group and the
treatment group after the treatment. Therefore, determination of quality of life changes can be
effectively achieved through completion of quality of life questionnaire by the study participants
upon the end of the treatment. This is a vital aspect in anticipating the best approach to curb
adverse effects associated with the treatment.
Tittle of Protocol Section: Eligibility Criteria (Screening)
Previous Text:
Women of child-bearing potential will undergo a serum pregnancy test prior the study
environment. In addition, a blood sample will be collected on all patients at screening to ensure
the lab values are within required range to confirm eligibility of the patient. To limit unnecessary
venipuncture, if the patient has had required laboratory tests performed within the last 2 weeks,
prior to screening, the results from this test may be utilized for screening.
Revised Text:
Women of child-bearing potential will undergo a serum pregnancy test prior the study
environment. In addition, a blood sample will be collected on all patients at screening to ensure
the lab values are within required range to confirm eligibility of the patient. Furthermore, a CT
scan of the abdomen and pelvis as well as a bone scan will be performed as part of the screening
assessments associated with screening criterion #3. To limit unnecessary venipuncture, if the
patient has had required laboratory tests performed within the last 2 weeks, prior to screening,
the results from this test may be utilized for screening.

CLINICAL RESEARCH (TRIAL DESIGN) 5
Rationale:
Even though protocol version 1.0 present “clinical suspicion of metastatic disease” as an
exclusion criterion, no strategy for ascertaining the presence of the disease has been awarded.
This might render the protocol invalid as this criterion might be treated subjectively by someone
else. Therefore, contacting imaging scan is essential to ensure there is no evidence of metastatic
disease.
Tittle of Protocol Section: Intervention
Subtitle: DrugAB56 (Experiment Group)
Previous Text:
Pharmaceutical ABC Inc will supply the study drugAB56 AS 500mg strength tablets, contained
within a single bottle (36 tablets within each bottle).
Following randomization, study participants randomized to the DrugAB56 treatment
group will be provided with a single bottle of DrugAB56 along with administration instructions.
Treatment is to be administered on an outpatient basis. Study participants will take Drug AB56,
500mg once daily, (1 tablet) by mouth, every evening, with food, for a period of three months.
If a patient forgets to take DrugAB56 at the routinely scheduled time, it should be
skipped and resumed at the routinely scheduled time on the next scheduled day of dosing.

CLINICAL RESEARCH (TRIAL DESIGN) 6
Study participants will return to the clinic every month (30 days + or – 2 days).They are
instructed to bring their bottle of drugsAB56 tablets to each clinic visit. A pill count ill be
performed.
Revised Text:
Pharmaceutical ABC Inc will supply the study drugAB56 AS 500mg strength tablets, contained
within a single bottle (36 tablets within each bottle).
Following randomization, study participants randomized to the DrugAB56 treatment
group will be provided with a single bottle of DrugAB56 along with administration instructions.
Treatment is to be administered on an outpatient basis. Study participants will take Drug AB56,
500mg once daily, (1 tablet) by mouth, every evening, with food, for a period of three months.
If a patient forgets to take DrugAB56 at the routinely scheduled time, it should be
skipped and resumed at the routinely scheduled time on the next scheduled day of dosing.
Study participants will return to the clinic every month (30 days + or – 2 days).They are
instructed to bring their bottle of drugsAB56 tablets to each clinic visit. For each study
participant, hospital admissions and emergency room visits will be documented during the
treatment period. A pill count will be performed.

CLINICAL RESEARCH (TRIAL DESIGN) 7
Rationale:
During the treatment period, emergency room visits and hospital admissions are extra
costs. Such costs must be acknowledged while assessing the economics of an intervention.
Therefore, it is essential to document all emergency room visits and hospital admissions during
the study in order to effectively assess the cost effectiveness of the intervention.
Tittle of Protocol Section: Outcomes (Secondary Outcomes)
Previous Text:
1. Safety and tolerability of treatment will be summarized. All patients will be assessed for
the occurrence of adverse events from the time of their first treatment. Frequency and
severity of adverse events will be tabulated using counts and proportions detailing
frequently occurring adverse and serious events of interest.
2. Overall survival (OS), defined as the time from the first treatment to the date of death
from any cause.
3. Quality of life will be assessed with the SF-36 quality of life questionnaire to assess the
impact of quality of life.
4. Biomaker assessments will include analysis of archival tissue.
Revised Text:
1. Safety and tolerability of treatment will be summarized. All patients will be assessed for
the occurrence of adverse events from the time of their first treatment. Frequency and
severity of adverse events will be tabulated using counts and proportions detailing
frequently occurring adverse and serious events of interest.

CLINICAL RESEARCH (TRIAL DESIGN) 8
2. Overall survival (OS), defined as the time from the first treatment to the date of death
from any cause.
3. Quality of life will be assessed with the SF-36 quality of life questionnaire to assess the
impact of quality of life.
4. Biomaker assessments will include analysis of archival tissue.
5. Cost effectiveness shall be assessed.
Rationale:
A secondary objective encompassing health economics has to be incorporated in the
protocol. The need of this economic evaluation is to quantify the comparative costs of the
standard care therapy and the experimental therapy. The standard for quantification with respect
to economics evaluation calls upon inclusion of cost effectiveness analysis as a secondary
outcome.
Section B: Informed Consent Form (ICF)
Following the information provided, the data included in the consent form has to be
amended. Usually, participants must be informed off all the procedures that will be undertaken
within the study. Failure to do so, no study procedures, including those required for screening
can be performed. Therefore, why anticipating whether of not the information in the consent
should change, it is vital to anticipate if the recommended adjustments will affect the study. The
response in our case is “yes.” Some participants might neglect the study based on the fact that a
CT scan of the abdomen and pelvis shall be performed. In case adverse conditions arise from
performance of this process then participants might raise a law suit with claims that they were
not informed of CT scan in the first place. On the other side, some participants might object the

CLINICAL RESEARCH (TRIAL DESIGN) 9
ideology of quality of life questionnaire. Thus there willingness to participate in the study should
be ascertained through updating the information in the consent form such that the amendments
are included.