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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, 2018 | Dec. 31, 2017 | Dec. 31, 2016
Income tax benefit at federal statutory rate (21% for 2018 and 2017 and 35 % for 2016) | $ (21,263) | $ (23,024) | $ (19,300)
State and local income taxes net of federal tax benefit | (2,547) | (1,611) | (1,173)
Permanent items | 503 | 910 | 1,057
Rate change | (29) | 71,155 | 1,080
Expiration of attribute carryforwards | 2,183 | 918 | 559
Effect of ASU 2016-09 |  | (5,949) |
Research and development tax credits | (4,905) | (1,977) | (4,681)
Orphan drug credit |  | 564 | 1,798
Other | 18 | 1,639 | 822
Change in valuation allowance | 26,040 | (42,625) | 19,838
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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