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Note 8 - Income Taxes - Differences Between the Company's Effective Tax Rate and the Statutory Tax Rate (Details) - USD ($) $ in Thousands | 12 Months Ended
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Dec. 31, 2019 | Dec. 31, 2018 | Dec. 31, 2017
Income tax benefit at federal statutory rate (21% for 2019, 2018 and 2017) | $ (22,868) | $ (21,263) | $ (23,024)
State and local income taxes net of federal tax benefit | (1,591) | (2,547) | (1,611)
Permanent items | 691 | 503 | 910
Rate change | 625 | (29) | 71,155
Expiration of attribute carryforwards | 3,976 | 2,183 | 918
Effect of ASU 2016-09 |  |  | (5,949)
Research and development tax credits | (4,938) | (4,905) | (1,977)
Orphan drug credit |  |  | 564
Other | 281 | 18 | 1,639
Change in valuation allowance | 23,824 | 26,040 | (42,625)
Income tax expense | $ 0 | $ 0 | $ 0

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- Definition Amount of the difference between reported income tax expense (benefit) and expected income tax expense (benefit) computed by applying the domestic federal statutory income tax rates to pretax income (loss) from continuing operations attributable to the effect from the adoption of an accounting standards update. + References No definition available. + Details
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