Project 2 - Clinical Investigation Plan

A Clinical Investigation Plan (CIP) is any systematic investigation of a medical device that involves one or more human subjects. The CIP describes the rationale, objectives, design methodology, monitoring, conduct, record-keeping and the method of analysis for a clinical investigation.The CIP shall be a document developed by the sponsor and the clinical investigator(s). The CIP shall be designed in such a way as tooptimise the scientific validity and reproducibility of the results of the study in accordance with current clinical knowledge and practice so as to fulfil the objectives of the investigation.

There are several key statistical considerations that should be taken into account when designing a clinical investigation:

1. Sample size: The sample size is the number of participants in the study. It is important to determine the appropriate sample size based on the statistical power of the study, which is the probability that the study will detect a true difference between the experimental and control groups. A larger sample size increases the statistical power of the study, but also increases the cost and resources required to conduct the study.

2. Statistical analysis plan: A statistical analysis plan is a detailed description of the statistical methods that will be used to analyze the data from the study. It should specify the primary and secondary outcomes that will be measured, the statistical tests that will be used, and any assumptions or limitations of the analysis.

3. Statistical significance: Statistical significance is the probability that a difference or association between the experimental and control groups is due to a real effect, rather than chance. A commonly used threshold for statistical significance is p < 0.05, which means that there is a less than 5% chance that the difference is due to chance.

4. Confidence intervals: Confidence intervals provide a range of values within which the true population value is likely to fall, based on the sample data. They help to provide a sense of the precision of the estimate, and can be used to determine whether the difference between the experimental and control groups is statistically significant.

Risk, Risk Assessment and Risk Management

The risks that are involved with the patient monitor is that what if the machine catches fire or if the machine gives out inadequate pressure to the cuff or over pressuries the cuff. Also the risk the machine carries is battery exploding as well as the PCB not getting protected against accidental drops from high altitudes. Also the loss of data adds to the list of risk. So for this risk assessment the machine was actually run and dropped several times during the time of testing. Also the batteries were overcharged and seen if the PCB does not catch fire due to longer working hours. Now to make sure this does not happen, the machine's touch panel is made of material which has a protective layer over the glass panel of the touch panel. Because of this, the machine even if it breaks the glas will not go on and splatter around the floor rather stay intact. The machine still is operational with the help of the buttons that are present on the bottom right of the patient monitor. As for the batteries exloding, since overcharging a lithium-ion battery might lead it to exploding after sometime, the machine rejects the batterries before the window closes. Now how would the user know the machine has rejected the battery you may ask? The machine has an alarm in it, not with sevre warning but with the least amount of alarm severity. As for the machine's integrity for regarding the PCB not getting burnt and breaking when the machine falls. The machine is equipped with cooling mechanism which cools the PCB time to time. The housing of the PCB is made in such a way that when the machine if falls by accident the PCB does not feel the impact as much as it should so that its integrity is maintained.

Purpose of Investigation

This is an observational, cohort-based, single-site, prospective study conducted in accordance with ISO standards. The primary objectives are to evaluate the accuracy of the device's measurements/readings in comparison to a gold standard or standard of care patient monitor.

Objective of investigation

This is an observational, cohort-based, single-site, prospective clinical study enrolling up to 100 patients who are hospitalized in the internal ward. There is no control group. The primary objectives of the study are:

• Evaluate the body temperature measured by the ear unit and validate its accuracy.

• Evaluate the accuracy of SPO2 signals and results by comparing the readings to a gold standard device with a finger sensor.

• Evaluate the ECG and respiration signals recorded by the patch device by comparing them to the signals recorded by a patient monitor with standard leads.

The study will asses if the machine is working with keeping the safety of the patient in regard and is not causing any harm to the patient rather than proving useful for the patient.

Population criteria for eligibility

Everyone who is 18 years and older is eligible for the test. The patient whi wishes to apply for the trial needs to be hospitalized already in a hospital. Should allow the hospital to share their medical data with the company executive to check if the patient is eligible in the criteria. The test will be done on 100 consequent people and the results will then be checked with the other standard patient monitors already available in the market to see if the patient monitor do cross the required mark for the certification.

Application for Grant of permission to conduct clinical investigation of an investigational medical device IVD

• Biocompatibility study- By definition, a measurement of how compatible a device or material is with a biological system. “Ability of a medical device or a material to perform with an appropriate host response in a specific application”.
• Information specified in table 3 shall be submitted along with investigator's brochure as prescribed in table 4, clinical investigational plan as prescribed in table 5, case report form as prescribed in table 6, serious adverse event reported, if any, as prescribed in table 7, informed consent form as prescribed in table 8, investigator's undertaking as prescribed in table 9, of this schedule and ethics committee approval, if available, as prescribed in appendix VIII of schedule Y of the drugs and cosmetics rules, 945.
• Regulatory status in other countries, if any, on use of investigational medical device in other countries,Prescription based device
  Exclusion of certain age groups Warning about adverse device effect Information on withdrawn in any country by the manufacturer or by regulatory authority, such information shall also be furnished along with reasons Sponsor should submit the above information to the Central Licensing Authority during the entire duration of marketing of the said medical device in the Country.
• Proposed Instruction for use or direction for use and labels to be submitted along with application. Provided that after submission and approval by the central licensing authority, no change in the instructions for use shall be effected without such changes having been approved by the central licensing authority
• Report of clinical investigation should be in consonance with the format

A properly conducted risk analysis is essential in determining what clinical evidence may be needed for a particular device (see ISO 14971). A clinical investigation is generally required when the currently available data are insufficient to demonstrate conformity with the Essential Principles. This would be the case when the manufacturer’s risk analysis and the clinical evaluation of a medical device for a particular intended use, including new claims, shows that there are residual risks, including aspects of clinical performance, that have not been adequately addressed by the available data.

As described in ISO 14971, “residual risk” is the risk remaining after risk control measures have been taken. Risk control measures include inherent safety by design, protective measures in the medical device itself or in the manufacturing process, and information for safety. The decision to use a medical device in the context of a clinical procedure requires the residual risk to be balanced against the anticipated benefits of the procedure. A clinical investigation may be required to further elucidate the risk/benefit ratio in a defined patient population. Where uncertainty exists as to whether current data are sufficient to demonstrate conformity with the Essential Principles, discussion with the relevant regulatory authorities or conformity assessment bodies may be appropriate.

As a general principle, “the rights, safety and wellbeing of clinical investigation subjects shall be protected consistent with the ethical principles laid down in the Declaration of Helsinki” (ISO 14155). It is ethically important in deciding to conduct a clinical investigation that it should generate new data and answer specific safety and/or performance questions that remain unanswered by the current body of knowledge. The desire to protect human subjects from unnecessary or inappropriate experimentation must be balanced with the need to protect public health through the use of clinical investigations where they are indicated. In all cases, however, care must be taken to ensure that the necessary data are obtained through a scientific and ethical investigational process that does not expose subjects to undue risks or discomfort. The rights, safety and well-being of subjects are paramount, and appropriate trial design and conduct is essential to generate meaningful data.

There are several key statistical considerations that should be taken into account when designing a clinical investigation:

• Sample size: The sample size is the number of participants in the study. It is important to determine the appropriate sample size based on the statistical power of the study, which is the probability that the study will detect a true difference between the experimental and control groups. A larger sample size increases the statistical power of the study, but also increases the cost and resources required to conduct the study.
• Statistical analysis plan: A statistical analysis plan is a detailed description of the statistical methods that will be used to analyze the data from the study. It should specify the primary and secondary outcomes that will be measured, the statistical tests that will be used, and any assumptions or limitations of the analysis.
• Statistical significance: Statistical significance is the probability that a difference or association between the experimental and control groups is due to a real effect, rather than chance. A commonly used threshold for statistical significance is p < 0.05, which means that there is a less than 5% chance that the difference is due to chance.
• Confidence intervals: Confidence intervals provide a range of values within which the true population value is likely to fall, based on the sample data. They help to provide a sense of the precision of the estimate, and can be used to determine whether the difference between the experimental and control groups is statistically significant.
• Data management is also an important aspect of clinical investigation, as it involves the collection, storage, and analysis of the data generated from the study. This may include establishing processes for collecting and recording data, developing a database or other data management system, and ensuring that the data are accurate, complete, and secure. It is important to have robust data management practices in place in order to ensure the integrity and reliability of the study results.

When should a clinical investigation be undertaken?

Clinical investigations are necessary to provide the data not available through other sources (such as literature or preclinical testing) required to demonstrate compliance with the relevant Essential Principles (including safety, clinical performance and acceptability of risk/benefit ratio associated with its use). When a clinical investigation is conducted, the data obtained is used in the clinical evaluation process and is part of the clinical evidence for the device (see GHTF/SG5/N2 – “Clinical Evaluation”). For long established technologies, clinical investigation data that might be required for novel technologies may not be necessary. The available clinical data in the form of, for example, published literature, reports of clinical experience, post-market reports and adverse event data may, in principle, be adequate to establish the safety and performance of the device, provided that new risks have not been identified, and that the intended use(s)/purpose(s) has/have not changed.

The informed consent process typically involves providing study participants with written information about the study, including the purpose of the study, the procedures that will be performed, the potential risks and benefits of participation, and any alternatives to participation. It also involves giving study participants the opportunity to ask questions and to discuss their concerns with the research team.

In addition to obtaining informed consent from study participants, it is also important to ensure that the clinical investigation is conducted in compliance with all relevant laws, regulations, and guidelines. This may involve obtaining approval from an Institutional Review Board (IRB) or other regulatory body, and following specific protocols and procedures to ensure the ethical conduct of the study.

In terms of adverse events associated with the device, it is important to carefully monitor and document any adverse events or adverse reactions that occur during the course of the study. Adverse events are any negative or unintended effects that occur as a result of the investigational device or the study procedures, and they may range from mild side effects to serious injuries or deaths. It is important to report all adverse events to the appropriate regulatory authorities, and to take appropriate action to mitigate any risks to study participants.

Inclusion and exclusion criteria are used to specify the types of individuals who are eligible or ineligible to participate in a clinical investigation. These criteria are typically based on factors such as age, gender, medical history, current health status, and other characteristics that may affect an individual's ability to participate in the study or the interpretation of the study results.

Inclusion criteria are the criteria that must be met in order for an individual to be eligible to participate in a clinical investigation. These criteria are used to define the target population for the study and to ensure that the study is focused on a specific group of individuals who are most likely to benefit from the investigational product or intervention being tested.

Exclusion criteria are the criteria that disqualify an individual from participating in a clinical investigation. These criteria are used to exclude individuals who may be at higher risk for experiencing adverse events or who may not be able to comply with the study procedures. Exclusion criteria may also be used to eliminate individuals whose inclusion in the study might bias the results or interfere with the interpretation of the data.

Vulnerable populations, such as children, pregnant women, and individuals with certain disabilities, may require special considerations in the inclusion and exclusion criteria for a clinical investigation. It is important to carefully consider the potential risks and benefits of including these populations in a study, and to ensure that their rights and welfare are protected. In some cases, additional safeguards may be necessary to ensure that these populations are not unduly exposed to risks, and that they are able to provide informed consent in a way that is appropriate for their specific needs and abilities.

There may be circumstances in which it is necessary to suspend or prematurely terminate a clinical investigation. This may occur due to safety concerns, ethical concerns, or other reasons that compromise the integrity or validity of the study.

If a clinical investigation is suspended or terminated, it is important to carefully document the reasons for the decision and to communicate the decision to all relevant stakeholders, including study participants, regulatory authorities, and the scientific community. It is also important to have a plan in place for managing any ongoing risks or effects associated with the investigational product or intervention, and to ensure that the rights and welfare of study participants are protected.

In terms of publication policy, it is generally expected that the results of a clinical investigation will be published in a peer-reviewed scientific journal. This helps to ensure that the results of the study are disseminated to the scientific community and are subject to independent review and critique. In some cases, it may also be necessary to report the results of the study to regulatory authorities or other stakeholders, such as funding agencies or professional organizations.

Guidelines for early termination of a clinical trial should be established before any data review is undertaken. Interim data analyses in conjunction with the totality of available evidence provides the necessary framework from which Data and Safety Monitoring Boards can make informed and prudent recommendations. Controlled clinical trials should not be prematurely terminated for trivial reasons. Controlled clinical trials should not be terminated prematurely on economic grounds, particularly if the information to be gained adds substantially to the knowledge base on the therapy of disease states. Such, for example, is the case with the early stoppage of the CONVINCE trial, where the motives for its discontinuation were a presumed fiduciary responsibility to the stockholders since it was believed that its findings might not fall into the “blockbuster” category. Finally, continuation of a trial deemed to be futile is wasteful of resources and potentially unethical. This is the case in the ALLHAT study, wherein there was early termination of the doxazosin treatment limb because of an unacceptably high rate of CHF when doxazosin-treated patients were compared to those receiving chlorthalidone. Similarly, there was an early termination of the amlodipine treatment limb of the AASK trial. When amlodipine treated patients were compared to those receiving the ACE inhibitor ramipril there was a sufficient difference in rate of decline of renal function in proteinuric subjects that the Data and Safety Monitoring Board felt that discontinuation of the amlodipine treatment limb to be warranted.