Legal analysts examine unusual state clinical research requirements
From Guide to Good Clinical Practice, Thompson Publishing Group
Table of Contents
Informed consent
Age of consent
California requirements
Legally authorized representatives
Privacy issues
IRB registration
State law resources
Although federal laws set the basic standard for the conduct of human clinical research, states may impose research requirements that go beyond federal regulations or address a subject on which federal laws are silent. And, as is the case with federal law violations, failure to meet state clinical research requirements can lead to severe civil, criminal and regulatory penalties.
At the recent Drug Information Association (DIA) annual meeting in San Diego, two legal analysts examined some of the key areas of clinical study conduct where states have set their own requirements.
Informed consent
For example, most states have individual laws pertaining to informed consent. According to Gary Yingling, a food and drug attorney with McKenna and Cuneo in Washington, D.C., compliance with the FDA informed consent regulations (21 CFR §50.20) or the "Common Rule" governing federally funded studies (45 CFR §46.116) will likely translate to compliance with state-established requirements. However, some states have laws that may differ from the federal regulations.
For instance, although federal regulations permit clinical studies to be performed in emergency situations provided that certain steps for obtaining informed consent are taken, certain states may have laws that specifically prohibit this form of research. Other aspects of informed consent also warrant further study of individual state laws; differences in medical records privacy and institutional review board (IRB) requirements also exist.
"You're not always going to find as clear a picture as you're looking for in state laws, or you're going to find differences from state to state," Yingling told DIA attendees.
Age of consent
The age at which a subject can consent to participate in clinical research may vary at the state level because neither the FDA regulations nor the Common Rule specifically set a minimum consent age, Yingling said. For example, Alabama and Massachusetts allow subjects as young as 14 years of age to consent to participate in clinical trials, but California sets its minimum age of consent at 15; subjects must be 16 years of age to consent to study participation in Rhode Island and South Carolina.
Conversely, although most states have a minimum consent age of 18, some states require that study subjects be slightly older than the age of majority to consent to research participation, Yingling noted. Nebraska, for example, requires a minimum consent age of 19, and Puerto Rico sets its standard at 21 years of age.
For studies involving minors, researchers must obtain consent from parents or legal representatives but also need the assent of the participating child. In most states, the age of assent is seven, according to Yingling.
"So, for example, a study in the state of Maryland involving a 14-year old would need the parent's consent but also a statement from the 14-year old that he or she agrees to participate in the study," Yingling said.
California requirements
Some states also impose consent requirements in addition to federal requirements. California, for example, requires clinical investigators to provide subjects with a signed and dated copy of the "California Experimental Subjects Bill of Rights" in addition to the study consent form, according to John Isidor, an attorney and chairman of Schulman Associates Institutional Review Board (IRB) in Cincinnati. Violations of the California law are considered a misdemeanor and are subject to one year in jail and a $10,000 fine, Isidor told DIA attendees.
Under California law, all study protocols and consent forms involving Schedule I and Schedule II controlled substances must be reviewed and approved by the California Research Advisory Panel prior to study start—this is in addition to federally required IRB review and approval, according to Isidor. Violations of the California law also are considered criminal offenses and are subject to fines and imprisonment.
Legally authorized representatives
Another area where state law may set specific clinical study criteria is in the use of legally authorized representatives to make decisions for incapacitated adults participating in clinical trials. According to Isidor, most state "statutes don't address who can actually be the healthcare decisionmaker for incapacitated adults."
In those states that do have regulations relating to decisionmaking for individuals with diminished capacity, most assign consent responsibility to legally authorized representatives or guardians, such as spouses or adult children, Yingling said. In other states, health decisions may be made by assigned "medical representatives"—individuals specifically given consent power by the incapacitated adult prior to their incapacitation.
Florida, Kentucky and Oklahoma are unique in that they allow for proxy consent in situations where there is no legally authorized representative, Isidor said. Specifically, these three states have statutes describing a hierarchy of individuals who may make medical decisions on behalf of an incapacitated adult, starting with the spouse and followed by an adult child, an adult sibling and a close relative. Finally, if none of those people can be located, a close friend is permitted to make decisions for the incapacitated subject.
Privacy issues
In terms of regulations protecting the privacy of research subjects, the states take a very "inconsistent approach," according to Yingling. Primarily, states maintain laws designed to protect the privacy of medical records, which can include research-related procedures. The release of a subject's medical records requires the subjects' consent in most states, Yingling said.
Yet, there are discrepancies among the states as to how much information can be disclosed and to whom the information may be disclosed. For example, some states permit the release of certain highly sensitive medical data that may be contained in patient records, including HIV status, mental illness, genetic diseases or conditions, organ donations and vital statistics, according to Yingling. To whom this information may be disclosed is highly variable depending upon the state.
It also is often unclear whether state record confidentiality requirements are relevant for all patients or whether there are different requirements pertaining to those patients who are participating in clinical research, Yingling noted.
IRB registration
States also may require their IRBs to meet standards or registration requirements in addition to federal regulations.
For example, external or non local IRBs that are involved with clinical research in Massachusetts are required to sign an affiliation agreement with the state, according to Isidor. Massachusetts also requires physicians to pay a $50 registration fee to conduct clinical research in the state.
State law resources
Regardless of the inconsistencies in state regulation of clinical research, both speakers agreed that sponsors, clinical investigators, IRBs and contract research organizations are obligated to know the requirements of the states in which they are conducting research.
Although finding information about specific state research laws can be tricky, state and county departments of health, commercial databases and the Internet can be useful data sources. And, if clinical trial entities are willing and able to spend the resources, they should contact legal counsel, Isidor advised.
"An attorney is probably the best way [to learn about state research requirements]," Isidor said, "but it is not the most inexpensive way."
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