DAT scans qualified for trials

The research record

This is the project's file for this landmark, as written and checked. Sources are listed at the end; anything not yet confirmed is marked "Not yet verified".

Who

The Critical Path for Parkinson's (CPP) consortium of the Critical Path Institute, led by Diane Stephenson with Parkinson's UK and industry partners, submitted the request, using data from PPMI (landmark 24) and the placebo arm of the PRECEPT trial (landmark 169). The EMA's drug committee (CHMP) issued the opinion.

What happened

Some people enrolled in early Parkinson's trials have a normal dopamine-transporter scan ("scans without evidence of dopaminergic deficit", SWEDD; see landmark 24), so they may not have the disease, or progress very slowly, and dilute any drug effect. In 2015 the FDA issued a letter of support for DAT imaging as an exploratory enrichment biomarker, and on 7 October 2016 the EMA issued its own letter of support to the consortium. Neither was a formal qualification.

CPP's EMA submission analysed 672 early-stage patients (481 from PPMI and 191 from the placebo arm of PRECEPT); SWEDD made up 13% of PPMI and 14% of PRECEPT. Those with SWEDD progressed more slowly on the motor score: about 0.05 points per month against 0.18 with a DAT deficit, a difference of 0.13. In the EMA document, DAT imaging identified about 92% of those with clinically important worsening. Simulations suggested about 355 participants per arm in an enriched trial against about 475 in a non-enriched one (roughly 24% fewer) to detect a hypothetical 50% slowing with 80% power. The CHMP adopted the opinion on 26 April 2018 (document dated 29 May 2018); CPP announced it on 26 July 2018.

Why it moved us toward a cure

The qualification was prepared by the Critical Path for Parkinson's consortium (landmark 226). Slowing-the-disease trials are slow and costly because progression is variable. Excluding people with no dopamine loss makes trials smaller and more likely to detect a real effect. The same logic later drove the seed assay (landmark 9), which got a 2024 FDA letter of support.

Imaging of dopamine pathways began with fluorodopa PET in 1983 (landmark 274).

DaTscan had been approved for clinical use in Europe in 2000 and the US in 2011 (landmark 345).

Outcome

Advanced. The qualification covers enrichment in early motor Parkinson's trials of up to two years, using a single visual read of the scan. The EMA notes the scan does not separate Parkinson's from multiple system atrophy or progressive supranuclear palsy. It does not make DAT imaging mandatory.

Sources

• EMA qualification opinion EMA/CHMP/SAWP/765041/2017 (DAT imaging as enrichment biomarker); numbers above read from the PDF
• C-Path on the EMA letter of support, 7 Oct 2016
• Critical Path Institute announcement, 26 Jul 2018
• Clinical Trials Arena, 30 Jul 2018
• MJFF on the 2024 FDA letter (notes the 2015 DaTscan letter)
• Not yet verified: the FDA's 2015 letter itself (a search summary dated it 16 March 2015 and addressed it to C-Path's Coalition Against Major Diseases; the FDA PDF would not load); who sponsored PRECEPT (the EMA text calls it a Phase 2/3 placebo-controlled trial); how many trials have used the enrichment; whether the FDA has issued a formal qualification. No correction or challenge to the opinion found.