September 30, 2023

Developing clinical trial protocols: Pharmaceutical Regulatory Science

Developing clinical trial protocols Unit IV Clinical trials

Introduction to Clinical trials

Clinical trials are a type of research that studies new tests and treatments and evaluates their effects on human health outcomes. People volunteer to take part in clinical trials to test medical interventions including; drugs, cells and other biological products, surgical procedures, radiological procedures, devices, behavioral treatments and preventive care.

International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP) is an international ethical and scientific quality standard for the design, conduct, performance, monitoring, auditing, recording, analysis and reporting of clinical trials. It also serves to protect the rights, integrity and confidentiality of trial subjects.

It is very important to understand the background of the formation of the ICH-GCP guidelines as this, in itself, explains the reasons and the need for doing so.

Today, the ICH-GCP guidelines are used in clinical trials throughout the globe with the main aim of protecting and preserving human rights. GCP provides assurance that the data and reported results are credible and accurate and that the rights, integrity and confidentiality of trial subjects are respected and Protected.


Every clinical investigation begins with the development of a clinical protocol. The protocol is a document that describes how a clinical trial will be conducted (the objectives, design, methodology, statistical considerations and organization of a clinical trial) and ensures the safety of the trial subjects and Integrity of the data collected.

The clinical trial should be carried out in accordance with a written protocol agreed upon and signed by the investigator and the sponsor. Any changes subsequently required must be similarly agreed on and signed by the investigator and sponsor and appended to the protocol as amendments.

The protocol, appendices and any other relevant documentation should state the aim of the trial and the procedures to be used.

  • The reasons for proposing that it should be undertaken on humans.
  • The nature and degree of any known risks.
  • The groups from which it is proposed that trial subjects be selected and the means for ensuring that they are adequately informed before they give their consent.

According to the ICH Good Clinical Practice guidelines, a protocol should include the following topics:

1. General Information:

  • Protocol title, identifying number, version number and date.
  • Name and address of the sponsor and monitor (if other than the sponsor).
  • Name and title of the person authorized to sign the protocol and the protocol amendments for the sponsor.
  • Names and titles of the investigators responsible for conducting the study and the address and telephone number of the trial sites.
  • Name, title, address and telephone number of the sponsor’s medical expert.
  • Name, title, address and telephone number of the qualified physician who is responsible for all study related medical decisions.
  • Names and addresses of all institutions involved in the study (Including clinical laboratories and other medical or technical departments).
  • Addresses and telephone numbers of all clinical laboratories and/or institutions involved in the trial.

2. Background Information:

  • A description of the study is addressed, as well as its public health significance.
  • Findings from clinical or non-clinical studies may be significant to the proposed study.
  • Summary of the known potential risks and benefits to human participants.
  • A statement that the trial will be conducted in compliance with the protocol, GCP and the applicable regulatory requirement(s).
  • Description of the study population.
  • References to relevant literature and data.
  • If the study involves the use of an investigational product or therapy: Name and description of the investigational product or therapy. Description of and justification for the route of administration, dosage, dosage regimen and treatment period(s).

3. Study Objectives and Purposes:

A detailed description of the major (primary) and minor (secondary and exploratory) objectives and the purpose of the trial.

4. Study Design:

The scientific integrity of the study and the credibility of the data obtained from the study largely depend on the study design. This section of the protocol should describe:

  • Primary and secondary endpoints to be measured and how they will be measured.
  • Study type (e. g. double-blind), with a schematic diagram of the study design, procedures and stages.
  • Measures that will be taken to avoid or minimize bias (e. g. randomization, blinding).
  • Dosage and dosage regimen, dosage form, packaging and labeling of investigational products.
  • Expected duration of participant participation, sequence and duration of all study periods, including follow-up.
  • “Stopping rules” or “discontinuation criteria” for individual participants, parts of the study and the entire study.
  • Accountability procedures for the investigational product, including the placebo and comparator.
  • Maintenance of study treatment randomization codes and procedures for breaking codes.

5. Selection and Withdrawal of Participants:

  • Criteria for inclusion and exclusion of participants.
  • Procedures for withdrawal of participants:
  • When and how to withdraw participants from the study/ Investigational product treatment.
  • Type and timing of data to be collected for participants who withdraw from the study.
  • Whether and how participants are to be replaced.
  • Follow-up for participants withdrawn from trial treatment.

6. Treatment of Participants:

  • Pharmacological treatment:
  • Names of all products to be administered.
  • Doses.
  • Dosing schedules.
  • Method(s) of administration (i. e. oral, intramuscular).
  • Other medications or treatments permitted (including rescue medication) and not permitted before and/or during the study.
  • Other interventions (i.e. chiropractic, physical therapy, social therapy, behavioral therapy, counseling):
  • Name of intervention (i. e. Motivational interviewing, cognitive Behavioral Therapy).
  • Frequency of sessions.
  • Duration of each session.
  • Method of each intervention (ie. individual, group).
  • Treatment adherence.
  • All interventions:
  • Period(s) of intervention, including follow-up periods for participants in each group.
  • Procedures for monitoring participant compliance.
  • Identification of who will administer an intervention.

7. Assessment of Efficacy:

This section describes the methods that will be used to determine the success of the treatment, including:

  • Criteria for determining the treatment’s effectiveness.
  • Methods and timing for assessing, recording and analyzing the effectiveness criteria

8. Assessment of Safety:

This section describes how the study will be monitored and how adverse events will be dealt with.

  • Specification of safety criteria.
  • Methods and timing for assessing, recording and analyzing the safety criteria.
  • Procedures for obtaining reports of adverse events and illnesses experienced by participants during the study period and for recording and reporting these events including expedited reporting procedures.
  • Type and duration of follow-up of participants who experience adverse events.

9. Statistics:

This section describes the strategy for analyzing the data collected during the study including:

  • Statistical methods to be employed, including the timing of any planned interim analyses.
  • Total number of participants to be enrolled.
  • Reason for the Choice of sample size, including reflections on the power of the study and clinical justification.
  • Level of significance to be used.
  • Criteria for termination of the study.
  • Procedure for accounting for missing, unused and false data.
  • Procedures for reporting deviations from the statistical plan.
  • Selection of participants to be included in analysis.

10. Direct Access to Source Data or Documents:

The sponsor should ensure that the protocol or other written agreement specifies that study investigators or institutions will permit study-related monitoring, audits, IRB review and regulatory inspections by providing direct access to source data or documents.

11. Quality Control and Quality Assurance:

A detailed quality assurance plan describing the set of standards and controls that are in place to confirm that the execution of each step follows the agreed-upon plan is usually submitted as a separate document. The protocol should, however, provide a general description of the quality assurance methods.

12. Ethics:

This section should describe ethical considerations relating to the study and measures taken to protect human participants and maintain confidentiality of study data.

13. Data Management:

The data management plan describes the procedures that will ensure data integrity throughout the study and at all study sites, including:

  • A description of the data system design and development.
  • Data collection methods and activities.
  • Methods of data entry and editing.
  • Procedures for data monitoring, reporting and transfer.
  • Data recipients and procedures for data dissemination.

14. Financing and Insurance:

This section describes how the study will be financed and insured. In some research networks, these issues are addressed in a separate agreement and need not be included in the protocol.

15. Publication Policy:

This section describes the policies and procedures relating to publication of findings from the study. In some research networks, policies and guidelines are established for research for the publications planning process.

The trial results will also be published on public website. This website will not identify participants, but will provide a resource for clinical trial participants and those seeking clinical trial involvement, to inform themselves.

16. Supplements:

This section supplies any additional information that may be required, depending on the nature of the research. For example, the informed consent template, the therapy manual, a patient information handbook, etc. may be included as attachments.

Final Year B Pharm Notes, Syllabus, Books, PDF Subjectwise/Topicwise

Final Year B Pharm Sem VIIBP701T Instrumental Methods of Analysis Theory
BP702T Industrial Pharmacy TheoryBP703T Pharmacy Practice Theory
BP704T Novel Drug Delivery System TheoryBP705 P Instrumental Methods of Analysis Practical
Final Year B Pharm Sem VIIBP801T Biostatistics and Research Methodology Theory
BP802T Social and Preventive Pharmacy TheoryBP803ET Pharmaceutical Marketing Theory
BP804ET Pharmaceutical Regulatory Science TheoryBP805ET Pharmacovigilance Theory
BP806ET Quality Control and Standardization of Herbals TheoryBP807ET Computer-Aided Drug Design Theory
BP808ET Cell and Molecular Biology TheoryBP809ET Cosmetic Science Theory
BP810ET Experimental Pharmacology TheoryBP811ET Advanced Instrumentation Techniques Theory
BP812ET Dietary supplements and NutraceuticalsPharmaceutical Product Development

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