Matches in SemOpenAlex for { <https://semopenalex.org/work/W4220792492> ?p ?o ?g. }
- W4220792492 endingPage "100" @default.
- W4220792492 startingPage "83" @default.
- W4220792492 abstract "Given the acknowledged lack of success in Alzheimer’s disease (AD) drug development over the past two decades, the objective of this review was to derive key insights from the myriad failures to inform future drug development. A systematic and exhaustive review was performed on all failed AD compounds for dementia (interventional phase II and III clinical trials from ClinicalTrials.gov) from 2004 to the present. Starting with the initial ∼2,700 AD clinical trials, ∼550 trials met our initial criteria, from which 98 unique phase II and III compounds with various mechanisms of action met our criteria of a failed compound. The two recent reported phase III successes of aducanumab and oligomannate are very encouraging; however, we are awaiting real-world validation of their effectiveness. These two successes against the 98 failures gives a 2.0% phase II and III success rate since 2003, when the previous novel compound was approved. Potential contributing methodological factors for the clinical trial failures were categorized into 1) insufficient evidence to initiate the pivotal trials, and 2) pivotal trial design shortcomings. Our evaluation found that rational drug development principles were not always followed for AD therapeutics development, and the question remains whether some of the failed compounds may have shown efficacy if the principles were better adhered to. Several recommendations are made for future AD therapeutic development. The whole database of the 98 failed compounds is presented in the Supplementary Material." @default.
- W4220792492 created "2022-04-03" @default.
- W4220792492 creator A5005301360 @default.
- W4220792492 creator A5006443278 @default.
- W4220792492 creator A5016072797 @default.
- W4220792492 creator A5028763778 @default.
- W4220792492 creator A5029379809 @default.
- W4220792492 creator A5058910594 @default.
- W4220792492 date "2022-05-03" @default.
- W4220792492 modified "2023-10-14" @default.
- W4220792492 title "Alzheimer’s Disease: Key Insights from Two Decades of Clinical Trial Failures" @default.
- W4220792492 cites W1480745369 @default.
- W4220792492 cites W1568866447 @default.
- W4220792492 cites W1798009377 @default.
- W4220792492 cites W1804731458 @default.
- W4220792492 cites W1824074994 @default.
- W4220792492 cites W1836722617 @default.
- W4220792492 cites W1976619844 @default.
- W4220792492 cites W1982816514 @default.
- W4220792492 cites W1983454097 @default.
- W4220792492 cites W2011347889 @default.
- W4220792492 cites W2015739499 @default.
- W4220792492 cites W2022012597 @default.
- W4220792492 cites W2035895733 @default.
- W4220792492 cites W2063808031 @default.
- W4220792492 cites W2086572083 @default.
- W4220792492 cites W2103440561 @default.
- W4220792492 cites W2105262354 @default.
- W4220792492 cites W2106223372 @default.
- W4220792492 cites W2109891655 @default.
- W4220792492 cites W2118935254 @default.
- W4220792492 cites W2142699659 @default.
- W4220792492 cites W2147048440 @default.
- W4220792492 cites W2168357345 @default.
- W4220792492 cites W2171645631 @default.
- W4220792492 cites W2221305104 @default.
- W4220792492 cites W2243723775 @default.
- W4220792492 cites W2273267066 @default.
- W4220792492 cites W2293751179 @default.
- W4220792492 cites W2306039713 @default.
- W4220792492 cites W2329336071 @default.
- W4220792492 cites W2385703614 @default.
- W4220792492 cites W2425513892 @default.
- W4220792492 cites W2505774393 @default.
- W4220792492 cites W2521624561 @default.
- W4220792492 cites W2532056566 @default.
- W4220792492 cites W2554957493 @default.
- W4220792492 cites W2567505071 @default.
- W4220792492 cites W2568450381 @default.
- W4220792492 cites W2581177196 @default.
- W4220792492 cites W2592672814 @default.
- W4220792492 cites W2596138682 @default.
- W4220792492 cites W2606278400 @default.
- W4220792492 cites W2609509800 @default.
- W4220792492 cites W2610795807 @default.
- W4220792492 cites W2616456751 @default.
- W4220792492 cites W2619653998 @default.
- W4220792492 cites W2740614417 @default.
- W4220792492 cites W2772872651 @default.
- W4220792492 cites W2782908288 @default.
- W4220792492 cites W2787612390 @default.
- W4220792492 cites W2790798430 @default.
- W4220792492 cites W2791937499 @default.
- W4220792492 cites W2797937217 @default.
- W4220792492 cites W2802659348 @default.
- W4220792492 cites W2884982789 @default.
- W4220792492 cites W2889787710 @default.
- W4220792492 cites W2891955176 @default.
- W4220792492 cites W2895806352 @default.
- W4220792492 cites W2900302187 @default.
- W4220792492 cites W2900856701 @default.
- W4220792492 cites W2912263089 @default.
- W4220792492 cites W2912754856 @default.
- W4220792492 cites W2937097483 @default.
- W4220792492 cites W2943828894 @default.
- W4220792492 cites W2944017202 @default.
- W4220792492 cites W2947686928 @default.
- W4220792492 cites W2949937187 @default.
- W4220792492 cites W2953246397 @default.
- W4220792492 cites W2955632681 @default.
- W4220792492 cites W2960505072 @default.
- W4220792492 cites W2962834367 @default.
- W4220792492 cites W2972924600 @default.
- W4220792492 cites W2974351167 @default.
- W4220792492 cites W2989656389 @default.
- W4220792492 cites W2997950680 @default.
- W4220792492 cites W3007686018 @default.
- W4220792492 cites W3023079706 @default.
- W4220792492 cites W3028460107 @default.
- W4220792492 cites W3044090667 @default.
- W4220792492 cites W3096878085 @default.
- W4220792492 cites W3107393058 @default.
- W4220792492 cites W3129955977 @default.
- W4220792492 cites W3167481375 @default.
- W4220792492 cites W4210839143 @default.
- W4220792492 cites W4211016192 @default.
- W4220792492 cites W4211139529 @default.
- W4220792492 doi "https://doi.org/10.3233/jad-215699" @default.