# Presentation: 856275

## Rare Genetic Diseases: Former SACGT Work Group and TFGT

- 		Michael Watson
- 		Mary Davidson
- 		Suzanne Haga
- 		Stephen Groft (ORD/NIH)
- 		Marlene Haffner (OPD/FDA)
- 		Vicky Whittemore

## Rare Genetic Diseases

- 20 -25 million individuals with one of more than 6,000 rare genetic diseases
- Includes acquired and heritable

## Prior Recommendations for Rare Genetic Disease Testing

- IOM (1994)
- Testing should be centralized in a few laboratories
- Set volume minimums
- Provisional premarket approval from FDA
- NIH/DOE Task Force on Genetic Testing
- Comprehensive data collection system
- Test validity
- Facilitate finding and using laboratories

## Rare Genetic Diseases: Regulatory Issues

- FDA Office of Orphan Product Development
- Drugs (Orphan Drug Act of 1983)
- Rare disease or condition means any that affects
- 	< 200,000 persons in US (1:1425)
- Market exclusivity for 7 years
- Research tax credits
- Grants
- Filing fee wavers (about $310,000)
- Devices (Humanitarian Device Exemptions) (SMDA 1990)
- Rare disease or condition means any that affects <4,000 people in US (1:71,250)
- Can not profit

## SACGT Recommendations

- SACGT recommends using disease incidence or prevalence as determinant of “rare”
- Prevalence less than <1 per 2,000
- Incidence of 1 per 10,000
- >90% of current genetic disease tests fit under this measure

## How the Genetics Paradigm Confounds Regulation

- Genetic heterogeneity
- Allelic
- About 25% of genes complex like *CFTR*
- Locus
- Variable expressivity
- One gene → more than one condition
- ApoE and CHD vs. AD
- FMR and FX vs. FXTAS
- Population variability in incidence and mutation spectrum
- Multiple intended uses

## Test Evolution

- Population-based Research
- Clinical Investigation
- Usually extended for rare diseases
- Diagnosis in affected and in family-based testing
- Screening
- Phenotypes
- Other risk groups (ethnic)
- General populations
- Standard of Care

## Research to Clinical PracticeCLIA

- CLIA Licensing
- Research Laboratories
- Partnerships between CLIA labs and investigators
-  Local institutional Laboratories
- External contract laboratories
- Limiting the leeway?
- Volume
- Other laboratories offering test

## ACMG/ASHG CLIA Compliance Survey

- Joann A. Boughman
- Michael S. Watson

## 	Who Responded

- “Research” laboratories
- Genetics and non-genetics
- CLIA and non-CLIA
- MD and non-MD

## 	       Response Rates

- 99 Laboratories
- 35 non-CLIA labs
- 8 non-genetic testing laboratories

## 	     Tests Being Done

- Most were using sequencing or scanning methods	for rare or unknown alleles
- 12 of 35 were doing more than 50 per year
- Most felt that providing specifics as to the test/condition tested would reveal them

## 	Among the 35 Non-CLIA 			          Respondents

- 16 NOT knowledgeable of Federal laws regulating clinical laboratories
- 19 claim to be knowledgeable

##  Among the 8 CLIA Non-Genetics Approved Laboratories

- 1 NOT knowledgeable of Federal laws regulating clinical laboratories
- 7 claim to be knowledgeable

## 	Among the 35 Non-CLIA 		Respondents

- 34 do not bill for testing
- 4 considered that if they didn’t bill, it wasn’t clinical testing
- 5 considered that if testing was paid by grant funds, it wasn’t clinical testing

## 	 Among the 8 CLIA Non-Genetics Approved Laboratories

- 1 does not bill for testing
- 4 considered that if they didn’t bill, it wasn’t clinical testing
- 5 considered that if testing was paid by grant funds, it wasn’t clinical testing

## 	Among the 35 Non-CLIA 				 Respondents

- 27 thought it too difficult to get a CLIA license
- 26 felt that if they didn’t provide testing, their patients wouldn’t have access

## Among the 35 Non-CLIA Labs

- Are you covered by your institutions malpractice coverage
- No -5			Don’t know - 11
- 8 labs felt that their research labs were covered because  they  were “practicing medicine”

## Comments from Non-CLIA Labs

- 5 labs indicated they were working with their clinical labs
- 3 labs indicated they were going to pursue licensing

## Types of Assistance Needed

- 18 non-CLIA labs needed guidance with protocol books   (34 total)
- 19 needed guidance to develop QA programs     (43 total)
- 11 wanted help finding clinical labs willing to take on new tests    (17 total)
- 12 wanted workshops and meetings    (31 total)

## Recent Developments of Rare Diseases Resources

- Office of Rare Diseases
- Enhanced funding
- Rare Diseases Centers
- Genetic and Rare Disease Information Center (with NHGRI)
- Genetic Alliance
- NORD