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Income taxes - Tax Rate Reconciliation (Details) | 12 Months Ended
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Dec. 31, 2021 | Dec. 31, 2020 | Dec. 31, 2019
Reconciliation of the U.S. statutory income tax rate to the entity's effective tax rate |  |  |
Federal income tax provision at statutory rate | 21.00% | 21.00% | 21.00%
State income tax provision, net of federal benefit | (0.74%) | (3.31%) | 1.08%
Permanent differences | (4.06%) | (6.66%) | (6.17%)
Research and development | 4.50% | 4.93% | 4.38%
Change in valuation allowances | (29.03%) | (26.40%) | (35.49%)
Change in deferred tax assets | 0.1205 | 0.0293 | 0.1589
Foreign tax rate differential | 0.01% | 0.72% | (1.88%)
Tax rate change | 0.01% | (1.46%) | (3.67%)
(Accrual) release of uncertain tax positions | (4.78%) | (0.61%) |
Other | (0.03%) | 0.12% |
Effective income tax rate | (1.07%) | (8.74%) | (4.86%)

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- Definition Percentage 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 changes in the valuation allowance for deferred tax assets. + References Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef -Publisher FASB -Name Accounting Standards Codification -Topic 740 -SubTopic 10 -Section S99 -Paragraph 1 -Subparagraph (SAB Topic 6.I.Fact.4) -URI http://asc.fasb.org/extlink&oid=122134291&loc=d3e330036-122817 Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef -Publisher FASB -Name Accounting Standards Codification -Topic 740 -SubTopic 10 -Section 50 -Paragraph 12 -URI http://asc.fasb.org/extlink&oid=121826272&loc=d3e32687-109319 + Details
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