Overview of U.S. Medical Device Clinical Trials

March 8, 2016 - Liz Scheurer, Principal Clinical Research Scientist, Neurocritical Care; and Lael Pickett

Clinical study conduct and design is always a challenge, with patient safety being at the forefront of that challenge. From an initial study concept, a company (“Sponsor”) must assess and implement decisions that will guide the project to the desired end. Is the study focusing on an iteration or small design change to an existing device or software? Is the device, therapy or expected action something novel, and is the study a “first-in-human” with the end result being a determination of “Is it safe and does it work?” All these factors need to be considered when human clinical evaluations are necessary. This paper will provide a brief overview of US clinical studies regulations, the types of clinical studies and how to determine if an Investigational Device Exemptions (IDE) is required.

The U.S. Food and Drug Administration (FDA) Guidance and Regulations

The U.S. FDA provides guidance on to how to answer questions about clinical studies along with regulations found in 21 CFR § 812 Investigational Device Exemptions (IDE). The IDE regulations provide criteria that can be used by study Sponsors to determine the appropriate type of clinical study to support their project. The Sponsor must make some preliminary assessments, such as the size of the study (number of subjects and centers) and the kind of data that needs to be collected (device functionality, safety, patient outcomes, etc.). Once the Sponsor has answers to these types of questions they can determine the appropriate study type. 

Types of Clinical Studies

There are four types of clinical studies:

1. Early Feasibility Study (EFS): N= <15 subjects. The device in question may be early in its development or a more finished prototype; design is not finalized in this type of study. “Is the device safe and does it work” is the desired end in an EFS study. EFS studies do not capture device efficacy data.

2. Feasibility Study: The study purpose is to capture preliminary safety and effectiveness device data, typically in a small number of subjects. Data from Feasibility Studies is usually used to determine safety and effectiveness criteria for the Pivotal Study.

3. Pivotal Study: The study purpose is to collect definitive evidence on safety and effectiveness for a specified intended use of the tested device, typically in a statistically justified number of subjects. Pivotal studies are “powered” for a robust data analysis.

4. Post Market Study: The study purpose is to collect long-term performance of the medical device in a more representative population.

Determining if an IDE is Required

With this study decision now in hand, the next step is to determine if an IDE is required. In the following diagram, the Sponsor is conducting a study with a medical device. Is the study “Exempt” from the IDE regulations, or is the Sponsor required to follow the IDE regulations (Figure 1)?

figure 1 us fda clinical study regulations by study type

Exempt Studies

“Exempt” clinical studies are referenced in 21CFR § 812.2(c) where the regulations speak to the applicability of the IDE regulations.

Is the device for the study a commercialized device used in accordance with their labeling, i.e. post market study? An example of an Exempt study would be a previously implanted pacemaker where data is being collected from interrogating the device with the programmer and the pacemaker is being used in accordance to its labeling.

Is the device for the study commercialized and is the intent of the study to test a consumer preference? Examples of consumer preference evaluations include the addition of colors to the device or obtaining feedback on a proposed new user interface. There are other types of Exempt device studies that are specified in the FDA IDE regulations. It is recommended that Sponsors document the study type decision, and be prepared to discuss the rationale for the decision to a regulatory body.

Non-Exempt Studies

“Non-Exempt” clinical studies are subject to the IDE regulations as outlined in 21 CFR § 812. Once the determination of study type had been made, the assessment of study risk further sets the level of regulatory oversight of the study. Figure 1 above divides study risk into two arenas; “Non-Significant Risk” and “Significant Risk” Studies.

Significant Risk Studies (SR): Defined in 21 CFR § 812.3(m)

Means an investigational device that:

  1. Is intended as an implant and presents a potential for serious risk to the health, safety, or welfare of a subject. An implant is defined in 21 CFR § 812.3(d) as ”A device that is placed into a surgically or naturally formed cavity of the human body if it is intended to remain there for a period of 30 days or more. FDA may, in order to protect public health, determine that devices placed in subjects for shorter periods are also ‘implants’ for purposes of this part.”
  2. Is purported or represented to be for a use in supporting or sustaining human life and presents a potential for serious risk to the health, safety, or welfare of a subject;
  3. Is for a use of substantial importance in diagnosing, curing, mitigating, or treating disease, or otherwise preventing impairment of human health and presents a potential for serious risk to the health, safety, or welfare of a subject; or
  4. Otherwise presents a potential for serious risk to the health, safety, or welfare of a subject.

The regulatory oversight of a SR study falls primarily to the Food and Drug Administration (FDA) and secondarily to the local Institutional Review Board (IRB).

Non-Significant Risk Studies (NSR)

NSR studies do not meet the definition of a SR study. The regulatory oversight of an NSR study falls to the local IRB. The following table highlights key differences between NSR and SR clinical studies (Table 1).

table 1 key nsr/sr study differences chart

Regardless of the study type, all clinical studies require an investigational plan that includes:

  • Clinical Protocol
  • Informed Consent Form
  • Case Report Forms
  • Data analysis plan which addresses the questions the study is trying to answer
  • Additional requirements apply to studies that are non-Exempt e.g., Reporting, Clinical Monitoring

Good study management is always required to maintain data integrity, patient safety, regulatory compliance and Sponsor expectations.

Minnetronix is committed to patient safety in the conduct of clinical trials. Because of our extensive experience with medical device development and a flexible manufacturing environment, we can support our customers with limited clinical builds. Additionally, we work closely with our customers, providing them with Minnetronix developed product design and/or manufacturing information to ensure successful clinical study applications.