Table 1 Emerging Trends in Rare Disease Research with Consent Implications

1. Increased complexity of research methods

 • Researchers are increasingly exploring new approaches to identify rare genetic variants resulting in increased complexity and diversity of research methods and protocols;

 • Clinical care often involves research in the context of specialty clinics providing care for rare disease patients.

Consent implications:

 • Consent forms risk becoming lengthy, technical and complicated;

 • The study purpose and potential benefits must be clearly stated to manage participant expectations and provide them with the necessary information to make informed decisions.

2. Increased family enrollment as a unit

 • Family members can provide important information in identifying the cause of a rare genetic disease (increased diagnostic rate – singleton vs. trio analysis) or help identify de novo mutations in a family;

 • Establishment of family pedigrees to allow linkage of family data.

Consent implications:

 • Although each family member may undergo individual consent interviews, often families are recruited using one consent document to address ethical and administrative challenges (i.e., no distinction made between “affected” and “unaffected” family members in consent forms);

 • Disclose privacy protections for use and sharing of family data;

 • Address possible coercion or undue inducement from family members participating in research study;

 • Address the return of results to family members;

 • Provide the possibility to notify family members of research results in case of the participant’s incapacity or death.

3. Increased data collection (amount, type & frequency)

 • Types of data collected: medical (e.g., clinical test results, diagnoses), health (e.g., administrative, self-reported data, sociodemographic), family history, genetic and phenotypic data;

 • Data sources: hospitals, private clinics, research, registries, social network sites;

 • Ongoing data acquisition from medical records.

Consent implications:

 • Disclose information, privacy and identifiability risks to participants and their family members.

4. Increased use of audiovisual data

 • 2–3 dimensional facial imaging used to identify and analyze patterns and similarities associated with facial dysmorphology;

 • Effective in identifying the underlying cause of rare diseases with computational phenotyping.

Consent implications:

 • Disclose information, privacy and identifiability risks to participants.

5. Increased global data sharing and linkage

 • Global data sharing, data linkage and international collaboration allow achieving sample sizes of statistical significance, richer datasets and ability to “match” similar genotypes/phenotypes for gene discovery in rare diseases;

 • Data linkage minimizes the burden on participants to submit new or additional data;

 • Large-scale data sharing and linkage increases complexity of data management and handling (e.g. access policies, security measures, data coordination, use of unique personal identifiers).

Consent implications:

 • Disclose information, privacy and identifiability risks to participants;

 • Inform participants of sharing process and limited right to withdraw data.