Study Protocols and their importance in clinical Studies

Zulfiqar Ali, Ph.D

Assistant Professor of Statistics, CSS, University of the Punjab, Lahore,

October 18, 2023

Introduction

  • This lecture is based on the importance of study protocols in clinical trials.
  • A well-designed clinical trial is a fundamental component of medical and scientific research.
  • In this lecture, we will discuss the significance of study protocols in ensuring the success and integrity of clinical trials.

What is a Study Protocol?

  • Every clinical trial needs a protocol.
  • A study protocol is essentially a written agreement among key stakeholders: the investigator, the participant, and the scientific community.
  • It outlines the essential details of the trial and provides a blueprint for its execution.

Purpose of the Study Protocol

  • The study protocol has several important purposes:
  • Background: It provides the context and background information for the trial.
  • Objectives: It clearly specifies the trial’s objectives and goals.
  • Design: It describes the trial’s design, including methodology and data collection.
  • Organization: It outlines the organizational aspects of the trial, including roles and responsibilities.

Detailed vs. Comprehensive

  • Not every complex detail of the trial needs to be in the protocol.
  • Comprehensive manuals of procedures can contain in-depth information.
  • The protocol should focus on the essential aspects and serve as a communication tool.

Facilitating Communication

  • The protocol aids in communication among individuals involved in the trial.
  • It ensures that everyone understands their roles and responsibilities.
  • Clear communication is crucial for the success of any clinical trial.

Sharing the Protocol

  • The protocol should be made available to others upon request.
  • Many protocols are now published in online journals, increasing transparency.
  • Sharing protocols contributes to scientific knowledge and reproducibility.

Timing of Protocol Development

  • The protocol should be developed before participant enrollment begins.
  • It serves as a guide for the entire trial process.
  • Minor updates may be made, but substantial changes can compromise the trial’s integrity.

Developing a Clinical Trials Protocol

  • A guidance document called the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT 2013 Statement) exists to help in developing clinical trials protocols.

  • Here are the typical topic headings found in a clinical trial protocol

Protocol Outline

Background of the study

B. Objectives

Primary question and response variable

Secondary questions and response variables

Subgroup hypotheses

Adverse effects

C. Design of the study

Study population

    1. Inclusion criteria
    1. Exclusion criteria

Sample size assumptions and estimates

Enrollment of participants

    1. Informed consent
    1. Assessment of eligibility
    1. Baseline examination
    1. Intervention allocation (e.g., randomization method)

Intervention(s)

    1. Description and schedule
    1. Measures of compliance

Follow-up visit description and schedule

Ascertainment of response variables

    1. Training
    1. Data collection
    1. Quality control

Assessment of Adverse Events

    1. Type and frequency
    1. Instruments
    1. Reporting

Data analysis

    1. Interim monitoring, including data monitoring committee role
    1. Final analysis

Termination policy

D. Organization

Participating investigators

    1. Statistical unit or data coordinating center
    1. Laboratories and other special units
    1. Clinical center(s)

Study administration

    1. Steering committees and subcommittees
    1. Monitoring committee
    1. Funding organization

Table 2.1 - Requirements for an Ethical Clinical Trial

Value

  • The first requirement is to evaluate an intervention that holds the potential to benefit society or advance scientific knowledge.

  • Clinical trials should address questions of significance and relevance to society or the scientific community.

  • Ethical research prioritizes studies that have value beyond mere experimentation.

Scientific Validity

  • Scientific validity is crucial for ethical trials. It involves using methods that are rigorous, reliable, and capable of producing meaningful results.

  • High-quality research methods ensure that the findings can be trusted and contribute to scientific knowledge. Slide

Fair Selection of Participants

  • Ethical trials require the fair selection of participants. This means avoiding placing vulnerable individuals at undue risk and preventing preferential access to attractive interventions for privileged individuals.

  • Equitable participant selection promotes fairness and justice in research.

Favorable Benefit/Risk Balance

  • It is essential to minimize risks and maximize potential benefits for participants.

  • Ethical trials should be designed with an estimate that the benefits are likely to outweigh the risks.

  • Evaluating and managing the benefit-to-risk ratio is crucial for participant safety.

Independent Review

  • Independent review is a safeguard in ethical research. It involves having individuals not directly affiliated with the research, such as ethics review committees, review the trial’s design.

  • This helps ensure impartial evaluation and adherence to ethical standards.

Respect for Enrolled Participants

  • Finally, respecting the rights and wellbeing of enrolled participants is paramount.

  • Researchers must protect participants from harm, ensure their confidentiality, and uphold their dignity throughout the trial.

  • Ethical conduct involves continuous monitoring and safeguarding of participants’ welfare.