Project 2 - Clinical Investigation Plan

Project 2

Clinical Investigation Plan (CIP):

It is a document stating the rationale, objective, design, proposed analysis, and record-keeping of the clinical investigation or clinical trial.

Identification of CIP

This consists of details by which one can identify the clinical trial uniquely. It consists of

• Title of clinical trial
• If applicable, the reference number identifying the specific clinical investigation
• Version number and date of the CIP
• If amendments took place, then a brief summary of revision history
• Version number with page number and total number of pages on each page of CIP

Overall synopsis

It includes all the clinical investigation design details like criteria for inclusion or exclusion of patients from the trial, number of subjects, duration of the trial, follow-ups and endpoint.

Justification of CI

Justification will be based on the conclusion of the evaluation that includes

• Evaluation of results of pre-clinical testing or any assessment that was carried out to justify the usage of device for humans
• Evaluation of clinical data that is relevant to the proposed clinical trial

Conducting the clinical investigation

Clinical investigation should be conducted only in accordance with the rules and permission granted by CLA. The Ethics Committee under the rule 122DD of Drugs and Cosmetic Rules, 1945 shall perform the functions and duties under these rules.

Application for grant of permission-An application for grant of permission to conduct a clinical trial for investigational medical device is made to CLA through Form MD-22 by sponsor.

Permission to conduct clinical trial is granted through Form MD-23.

Conditions for permission

Clinical trial is initiated after the approval by Ethics Committee and CI is registered with Clinical trial registry of India before enrolment of first subject. The trial should be started within 1 year of the grant of permission.

CI will be conducted in accordance with approved CIP and Good Clinical Practices issued by CDSCO. Annual status report should be submitted to CLA. In case of termination, reasons should be communicated to CLA within 30 days of termination.

In case of injury or death related to CI, compensation should be provided.

Responsibilities and Roles

Sponsor

• Sponsor is responsible for maintaining the quality assurance system to ensure that CI is designed, conducted and the data generated is recorded and documented in accordance with GCP issued by CDSCO
• Submit annual report to CLA along with safety summary and deviations
• Report adverse events to the Chairman of Ethics Committee, CLA and Head of the Institution
• Sponsor or his representative should submit the details of compensation paid for CI related injury or death within 30 days of receipt of order from CLA
• Reasons should be submitted in case of termination of trial.

Investigator

• Investigator is responsible for conduct of investigation according to CIP, GCP guidelines.
• Documented SOPs (Standard Operating Procedures) should be submitted for the tasks performed by them
• Investigator is responsible for ensuring that adequate medical care is provided and reporting the adverse events within 48 hours of its occurrence
• Investigator is responsible for providing consent form to the subject

Ethics committee

• Approves CIP in view of safety and well-being of all subjects
• Takes extra care In protecting vulnerable population
• Undertake an ongoing review of investigation of CIP
• Can revoke the approval to site and provide the reasons for its decision
• Any adverse events should be exported to the Chairman of Ethics committee after due analysis

Investigation site- It is an institution where clinical trial will be conducted.

Practical Identification & description of the investigational medical device

This section gives details of the investigational device, its identification summarized below

• Summary description of device
• Its intended medical purpose
• Details of the manufacturer of the device
• Model type, name and number of the device
• Traceability description to track the device
• Population and indications for usage of investigational medical device
• In case of contact with body tissues and fluids, description should be provided

Risks and benefits of investigational medical device

This section deals with the outcomes of risks and benefits that are due to the investigation like-

• Anticipated clinical benefits: It is about the benefits in clinical scenario like diagnostic or therapeutic benefits of the device
• Anticipated adverse device: The possible adverse effects are described
• Residual risks associated with the medical device
• Interactions with concomitant medical treatments
• Steps taken to control or mitigate the risk
• Risk to benefit rationale

Objectives and hypothesis of clinical investigation

• Objectives: The device’s objectives and how they will be achieved are described in the section. They are classified into
  • Primary objectives
  • Secondary objectives
• Hypothesis: It is the statement based on which the investigation moves forward. It is also classified as
  • Primary
  • Secondary
  • The hypothesis will either be accepted or rejected based on the statistical data
• Claims and intended performance evaluation
• Assessment of risks and anticipated adverse effects

Statistical considerations

This part gives the details of statistical data, collection and analysis of the data. The considerations employed in the CI listed below has to be verified and justified

• Statistical design, method and analytical methods
• Sample size: Based on what criteria sample size has been calculated
• The level of significance for CI has to be quantitatively presented
• Expected drop-out rates
• Pass or fail criteria for results of CI
• Provision for interim analysis
• Criteria for termination from trial on the statistical grounds
• Specifications of any sub-groups for analysis
• In case of multiple clinical investigational centres, the minimum and maximum number of subjects has to be specified

Data management

It describes how the data will be stored, how long and which way it is done. The main considerations are

• Procedures used for data review, database cleaning, issuing and resolving the queries
• Procedures to ensure the cyber safety and security of the clinical data systems, verification and validation of data
• Data retention steps
• Retention period
• Clinical quality assurance

Compliance statements

These are the standard statements like-

1. Statement specifying that clinical investigation shall be conducted according to ethical principles prescribed in GCP
2. Statement specifying that CI will not begin without approval from Ethics Committee
3. Statement stating that if any additional requirements are imposed by CLA or Ethics committee, it will be included and employed in conduct of CI
4. Statement specifying the type of insurance that will be provided for subjects

Informed consent

This is the important part of CI is to obtain informed consent from the subject participating in the CI

• The general description of informed consent process, the procedure to obtain it and the process of providing subjects with new information
• Description of informed consent process in scenarios where the subject is unable to give it, as in the case of emergency situations has to be clearly specified

Adverse events associated with the device

In this section, the description of adverse event, device defects and device deficiencies will be described

• Clear definition of adverse events, device adverse events and device deficiencies
• Defining serious adverse events
• Time period to report the adverse events to sponsor and if appropriate to Ethics committee and regulatory authority too
• Details of process to report the adverse events like date, treatment, resolution are to be mentioned
• List of foreseeable adverse events
• Emergency contact details in case of adverse events

Vulnerable population

In the section, vulnerable population is defined. The care to be taken while including them in CI or criteria to exclude them is defined.

• Vulnerable population is defined as a population group with hierarchical structures like prisoners, armed force personnel, medical or nursing staff, patients with incurable diseases, unemployed or impoverished subjects, patients in emergency situations, homeless and ethnic minority groups, nomads and refugees.
• Description of informed consent process for vulnerable group
• Description of ethics committee responsibility
• Description of inclusion and exclusion criteria

Necessities of suspension or premature termination of CI

• Criteria and arrangements in case of termination of CI in clinical sites has to be detailed
• Criteria to access the blinded and coded information wherever appropriate has to be mentioned
• Though the trial has been suspended, a method to follow-up with the subject is necessary

Publication policy

A clear statement has to be provided where if the results of CI are submitted for publication and also the conditions where the results of CI will be allowed for publication.