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1 - Alzheimer’s Disease Drug Development: A Research and Development Ecosystem

from Section 1 - Advancing Alzheimer’s Disease Therapies in a Collaborative Science Ecosystem

Published online by Cambridge University Press:  03 March 2022

By
Jeffrey Cummings ,
Jefferson Kinney  and
Howard Fillit
Edited by
Jeffrey Cummings ,
Jefferson Kinney  and
Howard Fillit
Jeffrey Cummings
Affiliation:
University of Nevada, Las Vegas
Jefferson Kinney
Affiliation:
University of Nevada, Las Vegas
Howard Fillit
Affiliation:
Alzheimer’s Drug Discovery Foundation
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Summary

Alzheimer’s disease (AD) drug development is a complex process that proceeds from identification of a biological target; to testing of candidate therapies in in vitro assays; assessment of efficacy in animal models and assessment of safety in several animal species; clinical testing in humans in Phase1, Phase 2, and Phase 3 clinical trials; regulatory review by agencies in all countries in which the drug might be marketed; and eventual commercialization. This process requires more than a decade to accomplish. The process involves substantial infrastructure resources; multiple stakeholders; and funding from a variety sources along the developmental pathway. This is the complex ecosystem that supports AD drug development.

Keywords

Alzheimer’s diseaseclinical trialsdrug developmentecosystemfundingventure capitalNIHcurriculumplatform trials
Type
Chapter
Information
Alzheimer's Disease Drug Development
Research and Development Ecosystem
 , pp. 1 - 24
Publisher: Cambridge University Press
Print publication year: 2022

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References

Scheltens, P, Blennow, K, Breteler, MM, et al. Alzheimer’s disease. Lancet 2016; 388: 505–17.Google Scholar
Masters, CL, Bateman, R, Blennow, K, et al. Alzheimer’s disease. Nat Rev Dis Primers 2015; 1: 15056.Google Scholar
Alzheimer’s Association. Alzheimer’s disease facts and figures. Alzheimer Dement 2019; 15: 321–87.Google Scholar
Alzheimer’s Disease International. World Alzheimer Report 2015: The Global Impact of Dementia. London: Alzheimer’s Disease International; 2015.Google Scholar
Cummings, JL, Morstorf, T, Zhong, K. Alzheimer’s disease drug-development pipeline: few candidates, frequent failures. Alzheimers Res Ther 2014; 6: 37.CrossRefGoogle ScholarPubMed
Wang, X, Sun, G, Feng, T, et al. Sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer’s disease progression. Cell Res 2019; 29: 787–803.CrossRefGoogle ScholarPubMed
Servick, K. Doubts persist for claimed Alzheimer’s drug. Science 2019; 366: 1298.Google Scholar
Cummings, J, Ritter, A, Zhong, K. Clinical trials for disease-modifying therapies in Alzheimer’s disease: a primer, lessons learned, and a blueprint for the future. J Alzheimers Dis 2018; 64: S3–22.CrossRefGoogle Scholar
Cummings, J, Fox, N. Defining disease modifying therapy for Alzheimer’s disease. J Prev Alzheimers Dis 2017; 4: 109–15.Google ScholarPubMed
Cummings, J. Disease modification and neuroprotection in neurodegenerative disorders. Transl Neurodegener 2017; 6: 25.Google Scholar
Fauman, EB, Rai, BK, Huang, ES. Structure-based druggability assessment: identifying suitable targets for small molecule therapeutics. Curr Opin Chem Biol 2011; 15: 463–8.Google Scholar
Ambure, P, Roy, K. Advances in quantitative structure–activity relationship models of anti-Alzheimer’s agents. Expert Opin Drug Discov 2014; 9: 697–723.CrossRefGoogle ScholarPubMed
Gimenez, BG, Santos, MS, Ferrarini, M, et al. Evaluation of blockbuster drugs under the rule-of-five. Pharmazie 2010; 65: 148–52.Google ScholarPubMed
Leeson, PD. Molecular inflation, attrition and the rule of five. Adv Drug Deliv Rev 2016; 101: 22–33.CrossRefGoogle ScholarPubMed
Hughes, JP, Rees, S, Kalindjian, SB, et al. Principles of early drug discovery. Br J Pharmacol 2011; 162: 1239–49.Google Scholar
Dragunow, M. High-content analysis in neuroscience. Nat Rev Neurosci 2008; 9: 779–88.CrossRefGoogle ScholarPubMed
Alqahtani, S, Mohamed, LA, Kaddoumi, A. Experimental models for predicting drug absorption and metabolism. Expert Opin Drug Metab Toxicol 2013; 9: 1241–54.CrossRefGoogle ScholarPubMed
Redfern, WS, Carlsson, L, Davis, AS, et al. Relationships between preclinical cardiac electrophysiology, clinical QT interval prolongation and torsade de pointes for a broad range of drugs: evidence for a provisional safety margin in drug development. Cardiovasc Res 2003; 58: 32–45.CrossRefGoogle ScholarPubMed
Bass, AS, Cartwright, ME, Mahon, C, et al. Exploratory drug safety: a discovery strategy to reduce attrition in development. J Pharmacol Toxicol Methods 2009; 60: 69–78.CrossRefGoogle ScholarPubMed
Freed, LM. Dose selection for first-in-human (FIH) trials: regulatory perspective. In Krishna, R, ed., Dose Optimization in Drug Development. New York, NY: Taylor & Francis Group, LLC; 2006: 45–60.Google Scholar
Presta, LG. Selection, design, and engineering of therapeutic antibodies. J Allergy Clin Immunol 2005; 116: 731–6.Google Scholar
Pul, R, Dodel, R, Stangel, M. Antibody-based therapy in Alzheimer’s disease. Expert Opin Biol Ther 2011; 11: 343–57.CrossRefGoogle ScholarPubMed
Sabbagh, JJ, Kinney, JW, Cummings, JL. Alzheimer’s disease biomarkers in animal models: closing the translational gap. Am J Neurodegener Dis 2013; 2: 108–20.Google ScholarPubMed
Puzzo, D, Gulisano, W, Palmeri, A, et al. Rodent models for Alzheimer’s disease drug discovery. Expert Opin Drug Discov 2015; 10: 703–11.CrossRefGoogle ScholarPubMed
Choi, SH, Kim, YH, Hebisch, M, et al. A three-dimensional human neural cell culture model of Alzheimer’s disease. Nature 2014; 515: 274–8.Google Scholar
Liu, Q, Waltz, S, Woodruff, G, et al. Effect of potent gamma-secretase modulator in human neurons derived from multiple presenilin 1-induced pluripotent stem cell mutant carriers. JAMA Neurol 2014; 71: 1481–9.Google Scholar
Umscheid, CA, Margolis, DJ, Grossman, CE. Key concepts of clinical trials: a narrative review. Postgrad Med 2011; 123: 194–204.Google Scholar
Cummings, JL. Translational scoring of candidate treatments for Alzheimer’s disease: a systematic approach. Dement Geriatr Cogn Disord 2020; 49: 22–37.CrossRefGoogle ScholarPubMed
Emilien, G, van Meurs, W, Maloteaux, JM. The dose–response relationship in phase I clinical trials and beyond: use, meaning, and assessment. Pharmacol Ther 2000; 88: 33–58.Google Scholar
Cummings, J. Lessons learned from Alzheimer disease: clinical trials with negative outcomes. Clin Transl Sci 2018; 11: 147–52.CrossRefGoogle ScholarPubMed
Dubois, B, Feldman, HH, Jacova, C, et al. Advancing research diagnostic criteria for Alzheimer’s disease: the IWG-2 criteria. Lancet Neurol 2014; 13: 614–29.Google Scholar
Rosen, WG, Mohs, RC, Davis, KL. A new rating scale for Alzheimer’s disease. Am J Psychiatry 1984; 141: 1356–64.Google ScholarPubMed
Morris, JC. The Clinical Dementia Rating (CDR): current version and scoring rules. Neurology 1993; 43: 2412–14.CrossRefGoogle ScholarPubMed
Cummings, JL. Optimizing phase II of drug development for disease-modifying compounds. Alzheimers Dement 2008; 4: S15–20.CrossRefGoogle ScholarPubMed
Cummings, J, Feldman, HH, Scheltens, P. The “rights” of precision drug development for Alzheimer’s disease. Alzheimers Res Ther 2019; 11: 76.Google Scholar
Greenberg, BD, Carrillo, MC, Ryan, JM, et al. Improving Alzheimer’s disease phase II clinical trials. Alzheimers Dement 2013; 9: 39–49.CrossRefGoogle ScholarPubMed
Gray, JA, Fleet, D, Winblad, B. The need for thorough phase II studies in medicines development for Alzheimer’s disease. Alzheimers Res Ther 2015; 7: 67.Google Scholar
Bateman, RJ, Munsell, LY, Morris, JC, et al. Human amyloid-beta synthesis and clearance rates as measured in cerebrospinal fluid in vivo. Nat Med 2006; 12: 856–61.Google Scholar
Kennedy, ME, Stamford, AW, Chen, X, et al. The BACE1 inhibitor verubecestat (MK-8931) reduces CNS beta-amyloid in animal models and in Alzheimer’s disease patients. Sci Transl Med 2016; 8: 363ra150.CrossRefGoogle ScholarPubMed
Portelius, E, Zetterberg, H, Dean, RA, et al. Amyloid-beta(1–15/16) as a marker for gamma-secretase inhibition in Alzheimer’s disease. J Alzheimers Dis 2012; 31: 335–41.CrossRefGoogle ScholarPubMed
Sevigny, J, Suhy, J, Chiao, P, et al. Amyloid PET screening for enrichment of early-stage Alzheimer disease clinical trials: experience in a Phase 1b clinical trial. Alzheimer Dis Assoc Disord 2016; 30: 1–7.Google Scholar
Sperling, RA, Jack, CR, Jr., Black, SE, et al. Amyloid-related imaging abnormalities in amyloid-modifying therapeutic trials: recommendations from the Alzheimer’s Association Research Roundtable Workgroup. Alzheimers Dement 2011; 7: 367–85.Google Scholar
Sperling, R, Salloway, S, Brooks, DJ, et al. Amyloid-related imaging abnormalities in patients with Alzheimer’s disease treated with bapineuzumab: a retrospective analysis. Lancet Neurol 2012; 11: 241–9.Google Scholar
Babiloni, C, Lizio, R, Marzano, N, et al. Brain neural synchronization and functional coupling in Alzheimer’s disease as revealed by resting state EEG rhythms. Int J Psychophysiol 2016; 103: 88–102.CrossRefGoogle ScholarPubMed
Sperling, RA, Dickerson, BC, Pihlajamaki, M, et al. Functional alterations in memory networks in early Alzheimer’s disease. Neuromolecular Med 2010; 12: 27–43.Google Scholar
Cummings, J, Zhong, K, Cordes, D. Drug development in Alzheimer’s disease: the role of default mode network assessment in phase II. US Neurol 2017; 13: 67.Google Scholar
Sevigny, J, Chiao, P, Bussiere, T, et al. The antibody aducanumab reduces Abeta plaques in Alzheimer’s disease. Nature 2016; 537: 50–6.Google Scholar
Sheiner, LB. Learning versus confirming in clinical drug development. Clin Pharmacol Ther 1997; 61: 275–91.CrossRefGoogle ScholarPubMed
Crous-Bou, M, Minguillon, C, Gramunt, N, et al. Alzheimer’s disease prevention: from risk factors to early intervention. Alzheimers Res Ther 2017; 9: 71.Google Scholar
Food and Drug Administration. Early Alzheimer’s Disease: Developing Drugs for Treatment. Guidance for Industry. US Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Center for Biologics Evaluation and Research (CBER); 2018.Google Scholar
Cummings, JL, Fox, N. Defining disease modification for Alzheimer’s disease clinical trials. J Prev Alzheimers Dis 2017; 4: 109–15.Google Scholar
Jack, CR, Jr., Bennett, DA, Blennow, K, et al. NIA-AA Research Framework: toward a biological definition of Alzheimer’s disease. Alzheimers Dement 2018; 14: 535–62.Google Scholar
Molinuevo, JL, Ayton, S, Batrla, R, et al. Current state of Alzheimer’s fluid biomarkers. Acta Neuropathol 2018; 136: 821–53.Google Scholar
Leber, P. Guidelines for the Clinical Evaluation of Antidementia Drugs. First draft. Technical Report. FDA Neuro-Pharm Group; 1990.Google Scholar
Karin, A, Hannesdottir, K, Jaeger, J, et al. Psychometric evaluation of ADAS-cog and NTB for measuring drug response. Acta Neurol Scand 2014; 129: 114–22.Google Scholar
Schmitt, FA, Ashford, W, Ernesto, C, et al. The Severe Impairment Battery: concurrent validity and the assessment of longitudinal change in Alzheimer’s disease. The Alzheimer’s Disease Cooperative Study. Alzheimer Dis Assoc Disord 1997; 11: S51–6.Google Scholar
Galasko, D, Bennett, D, Sano, M, et al. An inventory to assess activities of daily living for clinical trials in Alzheimer’s disease. The Alzheimer’s Disease Cooperative Study. Alzheimer Dis Assoc Disord 1997; 11: S33–9.CrossRefGoogle ScholarPubMed
Sikkes, SA, Pijnenburg, YA, Knol, DL, et al. Assessment of instrumental activities of daily living in dementia: diagnostic value of the Amsterdam Instrumental Activities of Daily Living Questionnaire. J Geriatr Psychiatry Neurol 2013; 26: 244–50.CrossRefGoogle ScholarPubMed
Zarit, SH, Reever, KE, Bach-Peterson, J. Relatives of the impaired elderly: correlates of feelings of burden. Gerontologist 1980; 20: 649–55.CrossRefGoogle ScholarPubMed
Logsdon, RG, Gibbons, LE, McCurry, SM, et al. Assessing quality of life in older adults with cognitive impairment. Psychosom Med 2002; 64: 510–19.CrossRefGoogle ScholarPubMed
Wimo, A, Winblad, B. Resource utilisation in dementia: RUD lite. Brain Aging 2003; 3: 48–59.Google Scholar
Donohue, MC, Sperling, RA, Salmon, DP, et al. The Preclinical Alzheimer Cognitive Composite: measuring amyloid-related decline. JAMA Neurol 2014; 71: 961–70.Google Scholar
Langbaum, JB, Ellison, NN, Caputo, A, et al. The Alzheimer’s Prevention Initiative Composite Cognitive Test: a practical measure for tracking cognitive decline in preclinical Alzheimer’s disease. Alzheimers Res Ther 2020; 12: 66.Google Scholar
Bateman, RJ, Benzinger, TL, Berry, S, et al. The DIAN-TU Next Generation Alzheimer’s prevention trial: adaptive design and disease progression model. Alzheimers Dement 2017; 13: 8–19.Google Scholar
Solomon, A, Kivipelto, M, Molinuevo, JL, et al. European Prevention of Alzheimer’s Dementia Longitudinal Cohort Study (EPAD LCS): study protocol. BMJ Open 2019; 8: e021017.Google Scholar
Cummings, JL, Froelich, L, Black, SE, et al. Randomized, double-blind, parallel-group, 48-week study for efficacy and safety of a higher-dose rivastigmine patch (15 vs. 10 cm(2)) in Alzheimer’s disease. Dement Geriatr Cogn Disord 2012; 33: 341–53.Google Scholar
Farlow, M, Veloso, F, Moline, M, et al. Safety and tolerability of donepezil 23 mg in moderate to severe Alzheimer’s disease. BMC Neurol 2011; 11: 57–64.Google Scholar
Cummings, J, Reiber, C, Kumar, P. The price of progress: funding and financing Alzheimer’s disease drug development. Alzheimers Dement (N Y) 2018; 4: 330–43.Google Scholar
DeTure, MA, Dickson, DW. The neuropathological diagnosis of Alzheimer’s disease. Mol Neurodegener 2019; 14: 32.CrossRefGoogle ScholarPubMed
Gersdorf, T, He, VF, Schlesinger, A, et al. Demystifying industry–academia collaboration. Nat Rev Drug Discov 2019; 18: 743–4.CrossRefGoogle ScholarPubMed
Silva, PJ, Ramos, KS. Academic medical centers as innovation ecosystems: evolution of industry partnership models beyond the Bayh–Dole Act. Acad Med 2018; 93: 1135–41.Google Scholar
Yokley, BH, Hartman, M, Slusher, BS. Role of academic drug discovery in the quest for new CNS therapeutics. ACS Chem Neurosci 2017; 8: 429–31.CrossRefGoogle ScholarPubMed
Ganem, D. Physician–scientist careers in the biotechnology and pharmaceutical industries. J Infect Dis 2018; 218: S20–4.Google Scholar
Slusher, BS, Conn, PJ, Frye, S, et al. Bringing together the academic drug discovery community. Nat Rev Drug Discov 2013; 12: 811–12.CrossRefGoogle ScholarPubMed
Wiederrecht, GJ, Hill, RG, Beer, MS. Partnership between small biotech and big pharma. IDrugs 2006; 9: 560–4.Google Scholar
Finkbeiner, S. Bridging the valley of death of therapeutics for neurodegeneration. Nat Med 2010; 16: 1227–32.Google Scholar
Parrish, MC, Tan, YJ, Grimes, KV, et al. Surviving in the valley of death: opportunities and challenges in translating academic drug discoveries. Annu Rev Pharmacol Toxicol 2019; 59: 405–21.CrossRefGoogle ScholarPubMed
Goldman, DP, Fillit, H, Neumann, P. Accelerating Alzheimer’s disease drug innovations from the research pipeline to patients. Alzheimers Dement 2018; 14: 833–6.Google Scholar
Reis, SE, Berglund, L, Bernard, GR, et al. Reengineering the national clinical and translational research enterprise: the strategic plan of the National Clinical and Translational Science Awards Consortium. Acad Med 2010; 85: 463–9.Google Scholar
Grill, JD, Di, L, Lu, PH, et al. Estimating sample sizes for predementia Alzheimer’s trials based on the Alzheimer’s Disease Neuroimaging Initiative. Neurobiol Aging 2013; 34: 62–72.Google Scholar
Holland, D, McEvoy, LK, Desikan, RS, et al. Enrichment and stratification for predementia Alzheimer disease clinical trials. PLoS One 2012; 7: e47739.Google Scholar
Kohannim, O, Hua, X, Hibar, DP, et al. Boosting power for clinical trials using classifiers based on multiple biomarkers. Neurobiol Aging 2010; 31: 1429–42.Google Scholar
McEvoy, LK, Edland, SD, Holland, D, et al. Neuroimaging enrichment strategy for secondary prevention trials in Alzheimer disease. Alzheimer Dis Assoc Disord 2010; 24(3): 269–77.CrossRefGoogle ScholarPubMed
Hendrix, JA, Finger, B, Weiner, MW, et al. The Worldwide Alzheimer’s Disease Neuroimaging Initiative: an update. Alzheimers Dement 2015; 11: 850–9.CrossRefGoogle Scholar
Iwatsubo, T, Iwata, A, Suzuki, K, et al. Japanese and North American Alzheimer’s Disease Neuroimaging Initiative studies: harmonization for international trials. Alzheimers Dement 2018; 14: 1077–87.Google Scholar
Grill, JD, Raman, R, Ernstrom, K, et al. Comparing recruitment, retention, and safety reporting among geographic regions in multinational Alzheimer’s disease clinical trials. Alzheimers Res Ther 2015; 7: 39.Google Scholar
Henley, DB, Dowsett, SA, Chen, YF, et al. Alzheimer’s disease progression by geographical region in a clinical trial setting. Alzheimers Res Ther 2015; 7: 43.Google Scholar
Moulder, KL, Snider, BJ, Mills, SL, et al. Dominantly Inherited Alzheimer Network: facilitating research and clinical trials. Alzheimers Res Ther 2013; 5: 48.CrossRefGoogle Scholar
Tariot, PN, Lopera, F, Langbaum, JB, et al. The Alzheimer’s Prevention Initiative Autosomal-Dominant Alzheimer’s Disease Trial: a study of crenezumab versus placebo in preclinical PSEN1 E280A mutation carriers to evaluate efficacy and safety in the treatment of autosomal-dominant Alzheimer’s disease, including a placebo-treated noncarrier cohort. Alzheimers Dement (N Y) 2018; 4: 150–60.Google Scholar
Lopez Lopez, C, Tariot, PN, Caputo, A, et al. The Alzheimer’s Prevention Initiative Generation Program: study design of two randomized controlled trials for individuals at risk for clinical onset of Alzheimer’s disease. Alzheimers Dement (N Y) 2019; 5: 216–27.Google ScholarPubMed
Ayutyanont, N, Langbaum, JB, Hendrix, SB, et al. The Alzheimer’s Prevention Initiative Composite Cognitive Test score: sample size estimates for the evaluation of preclinical Alzheimer’s disease treatments in presenilin 1 E280A mutation carriers. J Clin Psychiatry 2014; 75: 652–60.Google Scholar
Langlois, CM, Bradbury, A, Wood, EM, et al. Alzheimer’s Prevention Initiative Generation Program: development of an ApoE genetic counseling and disclosure process in the context of clinical trials. Alzheimers Dement (N Y) 2019; 5: 705–16.Google Scholar
Ritchie, CW, Molinuevo, JL, Truyen, L, et al. Development of interventions for the secondary prevention of Alzheimer’s dementia: the European Prevention of Alzheimer’s Dementia (EPAD) project. Lancet Psychiatry 2016; 3: 179–86.Google Scholar
Vermunt, L, Veal, CD, Ter Meulen, L, et al. European Prevention of Alzheimer’s Dementia Registry: recruitment and prescreening approach for a longitudinal cohort and prevention trials. Alzheimers Dement 2018; 14: 837–42.Google Scholar
Gregory, S, Wells, K, Forysth, K, et al. Research participants as collaborators: background, experience and policies from the PREVENT Dementia and EPAD programmes. Dementia (London) 2018; 17: 1045–54.Google Scholar
Romero, K, de Mars, M, Frank, D, et al. The Coalition Against Major Diseases: developing tools for an integrated drug development process for Alzheimer’s and Parkinson’s diseases. Clin Pharmacol Ther 2009; 86: 365–7.Google Scholar
Romero, K, Ito, K, Rogers, JA, et al. The future is now: model-based clinical trial design for Alzheimer’s disease. Clin Pharmacol Ther 2015; 97: 210–14.Google Scholar
Cummings, J, Lee, G, Ritter, A, Sabbagh M, Zhong K. Alzheimer’s disease drug development pipeline: 2020. Alzheimers Dement (N Y) 2020; 6: e12050.Google Scholar
Aisen, P, Sperling, R, Cummings, J, et al. The Trial-Ready Cohort for Preclinical/Prodromal Alzheimer’s Disease (TRC-PAD) project: an overview. J Prev Alzheimers Dis 2020; 7: 208–12.Google Scholar
Cummings, J, Aisen, P, Barton, R, et al. Re-engineering Alzheimer clinical trials: Global Alzheimer’s Platform network. J Prev Alzheimers Dis 2016; 3: 114–20.Google Scholar
Lamberti, MJ, Wilkinson, M, Harper, B, et al. Assessing study start-up practices, performance, and perceptions among sponsors and contract research organizations. Ther Innov Regul Sci 2018; 52: 572–8.CrossRefGoogle ScholarPubMed
Drabu, S, Gupta, A, Bhadauria, A. Emerging trends in contract research industry in India. Contemp Clin Trials 2010; 31: 419–22.CrossRefGoogle ScholarPubMed
Jack, CR, Jr., Albert, MS, Knopman, DS, et al. Introduction to the recommendations from the National Institute on Aging–Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 2011; 7: 257–62.Google Scholar
Prina, AM, Mayston, R, Wu, YT, et al. A review of the 10/66 dementia research group. Soc Psychiatry Psychiatr Epidemiol 2019; 54: 1–10.CrossRefGoogle ScholarPubMed
Abdin, E, Vaingankar, JA, Picco, L, et al. Validation of the short version of the 10/66 dementia diagnosis in multiethnic Asian older adults in Singapore. BMC Geriatr 2017; 17: 94.Google Scholar
Stewart, R, Guerchet, M, Prince, M. Development of a brief assessment and algorithm for ascertaining dementia in low-income and middle-income countries: the 10/66 short dementia diagnostic schedule. BMJ Open 2016; 6: e010712.Google Scholar
Winblad, B, Amouyel, P, Andrieu, S, et al. Defeating Alzheimer’s disease and other dementias: a priority for European science and society. Lancet Neurol 2016; 15: 455–532.CrossRefGoogle ScholarPubMed
Georges, J, Jansen, S, Jackson, J, et al. Alzheimer’s disease in real life: the dementia carer’s survey. Int J Geriatr Psychiatry 2008; 23: 546–51.Google Scholar
Keller, K, Briggs, L, Riley, E. Alzheimer’s Disease: A Center for Strategic Philanthropy Giving Smarter Guide, 2018; Available at: https://milkeninstitute.org/sites/default/files/reports-pdf/FINAL-Alz-GSG2.pdf.Google Scholar
Hara, Y, McKeehan, N, Fillit, HM. Translating the biology of aging into novel therapeutics for Alzheimer disease. Neurology 2019; 92: 84–93.Google Scholar
Lopez, JC, Suojanen, C. Harnessing venture philanthropy to accelerate medical progress. Nat Rev Drug Discov 2019; 18: 809–10.Google Scholar
Food and Drug Administration. Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA Products: Guidance for Industry. US Department of Health and Human Services Food and Drug Administration. Center for Drug Evaluation and Research (CDER) Center for Biologics Evaluation and Research (CBER); 2017.Google Scholar
Orr, D, Baram-Tsabari, A, Landsman, K. Social media as a platform for health-related public debates and discussions: the polio vaccine on Facebook. Isr J Health Policy Res 2016; 5: 34.Google Scholar
Kravitz, RL, Bell, RA. Media, messages, and medication: strategies to reconcile what patients hear, what they want, and what they need from medications. BMC Med Inform Decis Mak 2013; 13: S5.Google Scholar
Schulz, KF, Altman, DG, Moher, D, et al. CONSORT 2010 statement: updated guidelines for reporting parallel group randomized trials. Ann Intern Med 2010; 152: 726–32.Google Scholar
Galkina Cleary, E, Beierlein, JM, Khanuja, NS, et al. Contribution of NIH funding to new drug approvals 2010–2016. Proc Natl Acad Sci USA 2018; 115: 2329–34.CrossRefGoogle ScholarPubMed
Kosik, KS, Sejnowski, TJ, Raichle, ME, et al. A path toward understanding neurodegeneration. Science 2016; 353: 872–3.CrossRefGoogle ScholarPubMed
Saville, BR, Berry, SM. Efficiencies of platform clinical trials: a vision of the future. Clin Trials 2016; 13: 358–66.CrossRefGoogle ScholarPubMed
Adaptive Platform Trials C. Adaptive platform trials: definition, design, conduct and reporting considerations. Nat Rev Drug Discov 2019; 18: 797–807.Google Scholar
Kennedy, RE, Cutter, GR, Wang, G, et al. Challenging assumptions about African American participation in Alzheimer disease trials. Am J Geriatr Psychiatry 2017; 25: 1150–9.Google Scholar
Hall, AK, Mills, SL, Lund, PK. Clinician-investigator training and the need to pilot new approaches to recruiting and retaining this workforce. Acad Med 2017; 92: 1382–9.Google Scholar
Gehr, S, Garner, CC, Kleinhans, KN. Translating academic careers into industry healthcare professions. Nat Biotechnol 2020; 38: 758–63.Google Scholar
Thornicroft, G, Lempp, H, Tansella, M. The place of implementation science in the translational medicine continuum. Psychol Med 2011; 41: 2015–21.Google Scholar
Fort, DG, Herr, TM, Shaw, PL, et al. Mapping the evolving definitions of translational research. J Clin Transl Sci 2017; 1: 60–6.CrossRefGoogle ScholarPubMed
Dilworth-Anderson, P. Introduction to the science of recruitment and retention among ethnically diverse populations. Gerontologist 2011; 51: S1–4.CrossRefGoogle Scholar
Bauer, MS, Kirchner, J. Implementation science: what is it and why should I care? Psychiatry Res 2020; 283: 112376.Google Scholar
Sheeran, P, Klein, WM, Rothman, AJ. Health behavior change: moving from observation to intervention. Annu Rev Psychol 2017; 68: 573–600.Google Scholar
Rouse, R, Zineh, I, Strauss, DG. Regulatory science: an underappreciated component of translational research. Trends Pharmacol Sci 2018; 39: 225–9.Google Scholar

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