Special Research Categories

Jump to: Internet Research | International Research | Drugs and Devices | Investigational New Drug | Investigational Device Exemption | Research Involving Vulnerable Populations | Pregnant Women and Fetuses | Prisoners | Children | Workers | Department of Defense


Internet Research

Use of the internet to do research is relatively new. It has been used in human subjects research in many ways including recruiting and following up with subjects, administering surveys, and data mining as a source of research data (e.g., photographs of people). It presents unique challenges and concerns to the IRB and the researcher.

Protection of human subjects is no less important when using the internet than any other tool available to do human subjects research.  The following points should be considered when using the internet to do research: 

  • Not all content on the internet is “public” or “open source” information.
  • If an investigator is going to use a website, the terms and conditions of that site must be reviewed to make sure they are being followed.
  • Potential participants must still consent to participate unless the IRB has waived informed consent.
  • Participants must be adults, or parental permission must be obtained before collecting information from a minor.
  • When children are the participants in a study over the internet, the Children’s Online Privacy Protection Act must be followed in addition to 10 CFR 745.  Programs that check for internet monitoring or parental controls can be used to assist in identifying minors.
  • Privacy and the confidentiality of the information provided by participants must be protected.
  • Facial images obtained from or placed on the internet are considered personally identifiable information and may have implications with respect to privacy and confidentiality.

Read More: Considerations and Recommendations Concerning Internet Research and Human Subjects Research Regulations (Produced by the HHS Secretary’s Advisory Committee on Human Research Protections (SACHRP)).


International Research

All international human subjects research must adhere to recognized ethical codes including 45 CFR 46, the Declaration of Helsinki, The Nuremburg Code and the Belmont Report. The study must be reviewed by the IRB of record in the U.S.A.  Recruitment and consent documents must be in the language that is understandable to the participants.  They may be obtained using a written document that is readable by the participant or by use of the short form using a translator.

Countries may have procedures for protection of human subjects that differ from the U.S. federal regulations. The resources listed below are a compilation of research laws and regulations and of essential information for many countries in the world.

OHRP Compilation of International Human Subjects Laws contains listings of laws, regulations and guidelines on human subjects protection in over 100 countries and international organizations compiled by the Office of Human subjects Protection (OHRP)

Countries and Economies – World Bank provides comprehensive national data for developing countries around the world.

CIA Fact Book contains information about the history, people, government, economy, geography, communications, transportation, military and transnational issues for 267 countries of the world.

World Health Organization Country Information lists information including population statistics, information on the national health systems, mortality, disease burden and the health profile for each country that is a member of the United Nations.and the World Health Organization.


Drugs and Devices

Research that includes the clinical use of a drug or medical device that is new or not approved for that dosage, form, or indication must be reviewed according to the Food and Drug Administration (FDA) federal regulations found in 21 CFR 50.

Either an application for an Investigational New Drug (IND) or Investigational Device Exemption (IDE) may have to be completed.


Investigational New Drug

An IND Application is required if ANY of the following are TRUE about the product intended to be submitted to the FDA:

  • a new indication for use or for a significant change in labeling of the drug,
  • a significant change in advertising (e.g., for use in children as well as adults),
  • a different route of administration or dosage level,
  • use in a new, high-risk, and/or different patient population, or
  • other factor that significantly increases the risks or decreases the acceptability of the risks associated with use of the product.

The documents needed to prepare an IND include:

  • Form FDA 1571 (PDF) (IND Application) or a dossier addressing all of the elements outlined in Form 1571 must be submitted by the sponsor or sponsor-investigator.
  • Form FDA 1572 (Statement of Investigator)
  • Form FDA 3674 (PDF) (Certification of Compliance with Requirements of ClinicalTrials.gov Data Bank)

FDA Guidance to complete the IND application can be found in the following:

FDA Regulation of IND are the following:


Investigational Device Exemption

An IDE application is the document submitted to FDA to allow for the conduct of a clinical study using a significant risk device that is new or not approved for that use.

The FDA requirements for a new device depend on the potential risk of the device: significant, non-significant and exempt. 

  • Significant risk devices: An IDE is required to study an investigational device (including new intended use of an approved device) posing significant risk and must be submitted to FDA before study initiation. Significant risk is defined as a device that presents a potential serious risk to the health, safety, or welfare of subject (e.g., stents, sutures).
  • Non-significant risk devices: If the investigation involves the use of a device that does not pose significant risk to humans (a non-significant risk device), an IDE application to FDA is not required. Submissions for non-significant risk devices are made directly to the IRB. The sponsor-investigator must explain to the IRB why the device does not pose a significant risk.
  • IDE Exempt Investigation: The FDA may determine that your study is exempt from FDA regulation. However, the study is still subject to IRB regulation.

Additional information about FDA Regulation of the IDE is below.


Research Involving Vulnerable Populations

There are additional regulations beyond the basic requirements found in 10 CFR 745 Subpart A that must be followed when doing research with a vulnerable population. A “vulnerable population” is one that is considered compromised in its ability to make a voluntary and informed decision to participate in research. The federal regulations specifically define three such groups, namely pregnant women and fetuses, children and prisoners. The DOE also considers workers to be a vulnerable population. Other groups that are also considered vulnerable include the mentally challenged, and the economically or educationally disadvantaged.


Pregnant Women and Fetuses

Under Subpart B of 45 CFR 46, pregnant women and fetuses may be involved in research but the research must meet additional conditions. The conditions that must be met are specified by pre- and post-delivery and the viability of the fetus after delivery.

  • Sec 745.204  Research involving pregnant women or fetuses prior to delivery
  • Sec 745.205  Research involving fetuses after delivery
  • Sec 745.206  Research involving  the placenta, the dead fetus or fetal material after delivery
  • Sec 745.207  Research not otherwise approvable but presenting an opportunity to understand, prevent, or alleviate a serious problem affecting the health or welfare of pregnant women or fetuses

Prisoners

Subpart C of 45 CFR 46 applies to research in which prisoners are the subjects. While this subpart is directed at research funded by DHHS, DOE has chosen to apply this subpart to any research involving prisoners regardless of the funding source.

A prisoner is defined as an individual involuntarily confined or detained in a penal institution or other facility that provides an alternative to incarceration or criminal prosecution. This includes an individual who is detained pending arraignment, trial or sentencing.

As outlined in Subpart C, the IRB must also do the following in addition to what is required in Subpart A:

  • Make any modification to the composition of the IRB to satisfy the conditions in 45 CFR 46.304
  • Comply with the seven additional duties outlined in 45 CFR 46.305(a)
  • Restrict research to those areas defined in 45 CFR 46.306(a)(2)

There is additional guidance and FAQs regarding involvement of prisoners in research on the OHRP website.


Children

Special protections are provided in Subpart D of 45 CFR 46 when research involves children.  The regulations define a “child” as a person who has not reached “legal age” for consent to treatments or procedures that may involve research, under applicable laws of the jurisdiction in which the research is conducted.

When reviewing research involving children, the IRB must ensure that:

  • a risk-benefit analysis has been conducted that demonstrates the IRB’s understanding of and justification for the risks and benefits posed by approving research that includes children;
  • the research is in one of the permitted regulatory categories. See 45 CFR 46.401(b) and 404-407;
  • adequate provisions have been made to solicit parental permission; and
  • adequate provisions have been made to solicit assent of the child.

Refer to the additional guidance on the Office for Human Research Protections.


Workers

When individuals are invited to participate in research conducted at their work site or by their employer, they are potentially at risk from coercion, undue pressure and loss of confidentiality. In addition, former and retired workers may also be at risk if they are dependent upon employer-administrated pensions or benefits programs.

To guarantee knowledge of the work environment and of real or perceived risks faced by prospective workers, the IRB should include at least one worker as an IRB member or consultant when reviewing research proposals using workers. These additional points should be addressed:

  • There must be strict protections in place to protect the confidentiality of the participants. The threat increases when the participants are known to the researcher.
  • Although recruitment of employees is allowed, they may not be solicited on a personal basis, either face-to-face or via the phone. Acceptable recruitment methods include:
    • Posting IRB-approved flyers/ads
    • Sending IRB-approved invitations to employees who have expressed an interest in participating
  • PIs should not enroll employees who are in their supervisory chain

Department of Defense

The Department of Defense (DoD) regulations governing human subjects research are found in 32 CFR 219. The DoD also follows the FDA regulations. There is an additional DoD Instruction (DoDI) that must also be followed, namely3216.02 “Protection of Human Subjects and Adherence to Ethical Standards in DoD-Supported Research” (PDF). This DoDI contains additional requirements that address, but are not limited to the following:

  • Limitations on use of humans as experimental subjects
  • Limitations or restrictions on some Federal employees (both uniformed and civilian) regarding payment for research participation
  • Appointment of a medical monitor for all research that is greater than minimal risk to participants (The definition of a medical monitor may be found in DoDI 3126.02 (PDF), Section 4.4.3 and the definition of minimal risk is defined in 32 CFR 219.102(i), reference (c).)
  • When the research meets the DoD definition of “Research Involving a Human Being as an Experimental Subject,” the consent process may not be waived. (The definition may be found in DoDI 3216.02 (PDF), Enclosure 2. Definitions. Paragraph E2.1.3.)
  • Consent form language requirements