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IVD Clinical Trials & Development


In vitro diagnostic clinical trials, otherwise known as IVD clinical trials, are one of my direct therapeutic specialties as I worked as a Clinical Research Associate (CRA) for an in vitro diagnostic sponsor company for three and a half years. Below is a summary of what I know about IVD clinical trials.

In Vitro Diagnostics

So what are in vitro diagnostics (IVDs)? An in vitro diagnostic is a way to test for a certain property or result outside the human body. Some examples of in vitro diagnostic tests include testing blood for infectious pathogens, testing urine for pregnancy, and testing finger stick for blood glucose.

The FDA defines IVDs as:

In vitro diagnostic products are those reagents, instruments, and systems intended for use in the diagnosis of disease or other conditions, including a determination of the state of health, in order to cure, mitigate, treat, or prevent disease or its sequelae. Such products are intended for use in the collection, preparation, and examination of specimens taken from the human body. These products are devices as defined in section 201(h) of the Federal Food, Drug, and Cosmetic Act (the act), and may also be biological products subject to section 351 of the Public Health Service Act.

FDA 21 CFR 809.3(a)

IVDs are regulated under the definition of medical devices and fall under the requirements of medical device regulations in 21 CFR 812. Thus, they are categorized into 3 classes of medical devices.

Class I
These are devices where general controls are sufficient to provide reasonable assurance of the safety and effectiveness of the device. This is the lowest risk category. General controls include establishment registration, device listing, good manufacturing practices, labeling, and premarket notification. Class I devices are exempt from the IDE process and premarket review.

Class II
These devices pose a moderate risk to patients and are subjected to special controls in addition to general controls. Special controls may include additional labeling requirements, specific performance standards, and post market surveillance. Most class II IVDs need to go through premarket notification (510(k)) process. 510(k) approval may or may not require clinical trials.

Class III
These devices pose the highest risk to the patients. They are subject to investigational device exemption (IDE) application and premarket approval (PMA) requirements. PMA application usually requires clinical trials.

IVD Clinical Trials: Key Differentiators

Because in vitro diagnostic tests are done outside the human body, samples such as blood, urine, or tissue must be collected for the test. This allows clinical trials for IVDs to be much simpler (although not necessarily easier) to conduct when compared to drugs or medical devices. Below are some of the other unique aspects of IVD clinical trials.

Number of Clinical Sites Required

In general, the FDA requires clinical trials that evaluate the performance of an IVD to be evaluated at 3 or more clinical sites. One of these sites can be the manufacturer. IVD clinical trials can be done at a fewer number of sites when compared to drug clinical trials, where number of sites can be 10 or more.

Informed Consent Waiver for Some IVD Clinical Trials

Specifically, the FDA allows some IVD clinical trials to be conducted without the need for informed consent if the samples meet the following criteria (from Guidance on Informed Consent for In Vitro Diagnostic Device Studies Using Leftover Human Specimens that are Not Individually Identifiable – Guidance for Sponsors, Institutional Review Boards, Clinical Investigators and FDA Staff)

  1. The in vitro diagnostic test does not need IDE submission (see 21 CFR 812.2(c))
  2. Leftover specimens will be used (specimens for routine clinical care that would have been discarded)
  3. Specimens are not individually identifiable
  4. Individuals caring for the patients are different from those conducting the clinical trial
  5. Specimens are provided to the investigator(s) without identifiers that can uniquely identify the patient
  6. The clinical trial is overseen by an IRB following 21 CFR 56

Type of Clinical Evaluation Needed

The type of clinical evaluation needed for IVDs can vary depending on the intended use and the target specimen from patients. However, there are some common tests that are usually required for IVD performance evaluation. These may include precision, reproducibility, interference from other substances, measuring interval (range and cutoff), or expected clinical performance characteristics (e.g. sensitivity, specificity).

This is in contrast to drug trials, which aim to evaluate safety and efficacy of new drugs, and medical device trials, which assess the functional performance and safety of a medical device.

Level of On-site Monitoring Needed

IVD clinical trials are tests that produce results. As procedures for conducting an IVD test are set for clinical trials, the results of the test can usually be monitored remotely via email or fax. Thus, the number of monitoring visits normally conducted by the clinical trial monitor (Clinical Research Associate) for an IVD trial may be much less for an IVD clinical trial compared to drug or medical device trials.

Study Design

IVD clinical trials typically do not require randomization or placebos. They often involve comparing the new test’s results against those of an existing standard test to measure accuracy.

Drug clinical trials frequently involve randomized controlled trials with placebo groups to measure the drug’s therapeutic effect against no treatment or standard treatment, and medical device clinical trials might have control groups using standard treatment devices.

Sample Size & Data Handling

IVD clinical trials may need different sample sizes based on statistical requirements to prove effectiveness. Data handling may involve complex statistical analyses to correctly interpret performance.

Drug and medical device trials involve larger cohorts for statistical power to detect statistically significant clinical outcomes. This includes long-term follow-up data.

6. Clinical Trial Basics-IVD-Differences2
A comparison between IVD clinical trials and drug or medical device clinical trials

Author

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Ernie Sakchalathorn

Polachai Ernie Sakchalathorn is the founder of ClinicalResearchAssociateCRA.com and has been in clinical research since 2007. While he is no longer affiliated with the website or benefits financially from site operations, he still remains a professional in the clinical research space and currently serves as a Clinical Affairs Manager at a medical device company.

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