Table 3.

Potential regulatory barriers in clinical trial conduct and enrollment of a more diverse population

Country	Clinical trial application language	In-country sponsor presence/representation required	Specimen export regulations	Insurance and compensation	Key considerations while including vulnerable populations in clinical trials
					Children/minors	Neuro-divergent	Pregnant and nursing women
Australia	Unspecified	Yes	Yes	Sponsor should provide insurance and also explain to participants the compensation and/or treatment available to them in the event of trial-related injuries	•Age criteria: 18 years •Minors should be informed to the extent compatible with their maturity and understanding, and if capable, they should sign and personally date ICF •In addition, consent from a parent or guardian is also required	•Participant must consent if he/she has the capacity, or the participant’s LAR or guardian(s) must consent on behalf of the participant	•Well-being and care for the women who are pregnant, and their fetus always take precedence over research considerations
Brazil	Portuguese	No	Yes	Sponsor is responsible for providing insurance coverage for any unforeseen injury to research participants as well as to provide compensation to research participants and/or their legal heirs in the event of trial-related injuries or death	•Age criteria: unspecified •Child’s LAR and/or guardian(s) must sign the ICF	•Consent should only be provided once the participant is informed about the study, to the extent that the participant is able to understand it, and if able, the participant should sign and date the written informed consent in person •The participant’s LAR or guardian(s) must also be present during the informed consent process and sign and date the informed consent form	•Require additional safeguards to ensure that the participants are fully aware of the risks and that the research assesses the risks and benefits as well as any potential impact on fertility, pregnancy, the embryo or fetus, labor, lactation, and the newborn
Canada	English or French	Yes	Yes	Does not require the sponsor to provide insurance coverage or compensation for trial participants in the event of trial-related injuries or death	•Age criteria: unspecified •Child’s assent, in addition to the consent of an authorized third party, must be obtained	•Participants’ LAR or guardians can provide consent for adults who lack the capacity to decide on their behalf in accordance with the best interests of the persons concerned	•ICF should include a statement on the reasonably foreseeable risks or inconveniences to the participant and, when applicable, to an embryo, fetus, or nursing infant
China	Chinese	Yes	Yes (in collaboration with Chinese research institutions)	Sponsor is responsible for providing the investigator and clinical trial institution with legal and economic insurance or a guarantee related to the clinical trial, as well as to provide compensation to research participants in the event of trial-related injuries or death	•Age criteria: unspecified •ICF must be signed by the child’s LAR or guardian(s) •If the child can decide whether he/she is willing to participate, the ICF should also be approved by the child	•No relevant provisions regarding any special consent procedures	•No relevant provisions regarding any special consent procedures
India	English	Yes	Yes	Sponsor should provide insurance coverage or a provision in the budget for possible compensation for trial-related injuries as well as responsible for providing compensation to research participants and/or their legal heir(s) in the event of trial-related injuries	•Age criteria: <18 years •IC should be obtained from the LAR or guardian(s); however, all pediatric participants should be fully informed possible about the study in a language and in terms that they can understand	•Methods should be used to enhance the participants’ understanding	•Pregnant or nursing women should be included in clinical trials only when the drug is intended for use by pregnant or nursing women, fetuses, or nursing infants
UK	English	Yes	Yes	Sponsor and investigator are responsible for covering insurance and for providing compensation to research participants and/or their legal heirs in the event of trial-related injuries or death	•Age criteria: <16 years •ICF should be obtained from the LAR and/or guardian(s)	•IC should be obtained from the LAR and/or guardian(s)	•Participant Information Sheet should provide specific advice to potential participants about the risks related to pregnancy and breastfeeding while taking part in the research
United States	English	No	Yes	Insurance: not required Compensation: sponsor’s policies and procedures should address the costs of treatment of trial subjects in the event of trial-related injuries	•Age criteria: determined at the individual state level •ICF should be obtained from an LAR or both parents required unless one parent is deceased, unknown, incompetent, or not reasonably available, or when only one parent has legal responsibility for the care and custody of the child	•Investigator(s) must be informed about the condition and any level of impairment	•Requires additional safeguards
South Africa	English	Yes	Yes	Sponsor should provide insurance coverage or a provision in the budget for possible compensation for trial-related injuries as well as responsible to provide compensation to research participants and/or their legal heir(s) in the event of trial-related injuries	•Age criteria: <18 years •IC should be obtained from the LAR or guardian(s); however, all pediatric participants should be informed to the fullest extent possible about the study in a language and in terms that they can understand	•Methods should be used to enhance the participants’ understanding	•Pregnant or nursing women should be included in clinical trials only when the drug is intended for use by pregnant or nursing women, fetuses, or nursing infants

FDA, Food and Drug Administration; IC, informed consent; ICF, informed consent forms; ICH, International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use; LAR, legally authorized representative.