605:
it is determining whether a treatment will influence the disease. In an effectiveness study, it is essential that participants are treated as they would be when the treatment is prescribed in actual practice. That would mean that there should be no aspects of the study designed to increase compliance above those that would occur in routine clinical practice. The outcomes in effectiveness studies are also more generally applicable than in most efficacy studies (for example does the patient feel better, come to the hospital less or live longer in effectiveness studies as opposed to better test scores or lower cell counts in efficacy studies). There is usually less rigid control of the type of participant to be included in effectiveness studies than in efficacy studies, as the researchers are interested in whether the drug will have a broad effect in the population of patients with the disease.
596:
chooses not to consider this drug further, at least not at that maximally tolerated dose. If the estimated activity level exceeds 20%, the researcher will add more participants to get a better estimate of the response rate. A typical study for ruling out a 20% or lower response rate enters 14 participants. If no response is observed in the first 14 participants, the drug is considered not likely to have a 20% or higher activity level. The number of additional participants added depends on the degree of precision desired, but ranges from 10 to 20. Thus, a typical cancer phase II study might include fewer than 30 people to estimate the response rate.
790:, or on certain population groups such as pregnant women, who are unlikely to subject themselves to trials). The safety surveillance is designed to detect any rare or long-term adverse effects over a much larger patient population and longer time period than was possible during the Phase I-III clinical trials. Harmful effects discovered by Phase IV trials may result in a drug being withdrawn from the market or restricted to certain uses; examples include
513:(MTD)). If an additional unacceptable toxicity is observed, then the dose escalation is terminated and that dose, or perhaps the previous dose, is declared to be the maximally tolerated dose. This particular design assumes that the maximally tolerated dose occurs when approximately one-third of the participants experience unacceptable toxicity. Variations of this design exist, but most are similar.
636:
this stage include attempts by the sponsor at "label expansion" (to show the drug works for additional types of patients/diseases beyond the original use for which the drug was approved for marketing), to obtain additional safety data, or to support marketing claims for the drug. Studies in this phase are by some companies categorized as "Phase IIIB studies."
659:(NDA) containing all manufacturing, preclinical, and clinical data. In case of any adverse effects being reported anywhere, the drugs need to be recalled immediately from the market. While most pharmaceutical companies refrain from this practice, it is not abnormal to see many drugs undergoing Phase III clinical trials in the market.
786:) and ongoing technical support of a drug after it receives regulatory approval to be sold. Phase IV studies may be required by regulatory authorities or may be undertaken by the sponsoring company for competitive (finding a new market for the drug) or other reasons (for example, the drug may not have been tested for
1620:
The great strength of this trial is its "adaptive" nature. This means that ineffective experimental treatments can very quickly be dropped and replaced by other molecules that emerge from research efforts. We will therefore be able to make changes in real time, in line with the most recent scientific
626:
on large patient groups (300–3,000 or more depending upon the disease/medical condition studied) and are aimed at being the definitive assessment of how effective the drug is, in comparison with current 'gold standard' treatment. Because of their size and comparatively long duration, Phase III trials
405:
by establishing very early on whether the drug or agent behaves in human subjects as was expected from preclinical studies. Distinctive features of Phase 0 trials include the administration of single subtherapeutic doses of the study drug to a small number of subjects (10 to 15) to gather preliminary
604:
When a study assesses efficacy, it is looking at whether the drug given in the specific manner described in the study is able to influence an outcome of interest (e.g. tumor size) in the chosen population (e.g. cancer patients with no other ongoing diseases). When a study is assessing effectiveness,
508:
If unacceptable toxicity is observed in any of the three participants, an additional number of participants, usually three, are treated at the same dose. This is continued until pre-calculated pharmacokinetic safety levels are reached, or intolerable side effects start showing up (at which point the
667:
The design of individual trials may be altered during a trial – usually during Phase II or III – to accommodate interim results for the benefit of the treatment, adjust statistical analysis, or to reach early termination of an unsuccessful design, a process called an "adaptive design". Examples are
635:
It is common practice that certain Phase III trials will continue while the regulatory submission is pending at the appropriate regulatory agency. This allows patients to continue to receive possibly lifesaving drugs until the drug can be obtained by purchase. Other reasons for performing trials at
631:
medical conditions. Phase III trials of chronic conditions or diseases often have a short follow-up period for evaluation, relative to the period of time the intervention might be used in practice. This is sometimes called the "pre-marketing phase" because it actually measures consumer response to
651:
Once a drug has proved satisfactory after Phase III trials, the trial results are usually combined into a large document containing a comprehensive description of the methods and results of human and animal studies, manufacturing procedures, formulation details, and shelf life. This collection of
613:
Phase II clinical programs historically have experienced the lowest success rate of the four development phases. In 2010, the percentage of Phase II trials that proceeded to Phase III was 18%, and only 31% of developmental candidates advanced from Phase II to Phase III in a study of trials over
521:
Multiple ascending dose (Phase Ib): Multiple ascending dose studies investigate the pharmacokinetics and pharmacodynamics of multiple doses of the drug, looking at safety and tolerability. In these studies, a group of patients receives multiple low doses of the drug, while samples (of blood, and
481:
cancer or HIV and the treatment is likely to make healthy individuals ill. These studies are usually conducted in tightly controlled clinics called
Central Pharmacological Units, where participants receive 24-hour medical attention and oversight. In addition to the previously mentioned unhealthy
595:
In the first stage, the investigator attempts to rule out drugs that have no or little biologic activity. For example, the researcher may specify that a drug must have some minimal level of activity, say, in 20% of participants. If the estimated activity level is less than 20%, the researcher
690:
Adaptive designs within ongoing Phase II–III clinical trials on candidate therapeutics may shorten trial durations and use fewer subjects, possibly expediting decisions for early termination or success, and coordinating design changes for a specific trial across its international locations.
500:
Single ascending dose (Phase Ia): In single ascending dose studies, small groups of subjects are given a single dose of the drug while they are observed and tested for a period of time to confirm safety. Typically, a small number of participants, usually three, are entered sequentially at a
38:
743:
The amount of money spent on Phase II or III trials depends on numerous factors, with therapeutic area being studied and types of clinical procedures as key drivers. Phase II studies may cost as low as $ 7 million for cardiovascular projects, and as much as $ 20 million for
109:
If the drug successfully passes through Phases I, II, and III, it will usually be approved by the national regulatory authority for use in the general population. Phase IV trials are 'post-marketing' or 'surveillance' studies conducted to monitor safety over several years.
101:
Clinical trials testing potential medical products are commonly classified into four phases. The drug development process will normally proceed through all four phases over many years. When expressed specifically, a clinical trial phase is capitalized both in name and
430:
phrase "first-in-humans" in the 1990s; these trials are the first stage of testing in human subjects. They are designed to test the safety, side effects, best dose, and formulation method for the drug. Phase I trials are not randomized, and thus are vulnerable to
3351:
555:
is common, particularly when there is evidence of variation in metabolic rate. When the development process for a new drug fails, this usually occurs during Phase II trials when the drug is discovered not to work as planned, or to have toxic effects.
482:
individuals, "patients who have typically already tried and failed to improve on the existing standard therapies" may also participate in Phase I trials. Volunteers are paid a variable inconvenience fee for their time spent in the volunteer center.
470:, also called dose escalation studies, so that the best and safest dose can be found and to discover the point at which a compound is too poisonous to administer. The tested range of doses will usually be a fraction of the dose that caused harm in
652:
information makes up the "regulatory submission" that is provided for review to the appropriate regulatory authorities in different countries. They will review the submission, and if it is acceptable, give the sponsor approval to market the drug.
3296:
3252:
706:
A 2019 review of average success rates of clinical trials at different phases and diseases over the years 2005–15 found a success range of 5–14%. Separated by diseases studied, cancer drug trials were on average only 3% successful, whereas
438:
Normally, a small group of 20–100 healthy volunteers will be recruited. These trials are often conducted in a clinical trial clinic, where the subject can be observed by full-time staff. These clinical trial clinics are often run by
3341:
550:
or effect. Phase II trials are performed on larger groups (50–300 individuals) and are designed to assess how well the drug works, as well as to continue Phase I safety assessments in a larger group of volunteers and patients.
413:
A Phase 0 study gives no data on safety or efficacy, being by definition a dose too low to cause any therapeutic effect. Drug development companies carry out Phase 0 studies to rank drug candidates to decide which has the best
639:
While not required in all cases, it is typically expected that there be at least two successful Phase III trials, demonstrating a drug's safety and efficacy, to obtain approval from the appropriate regulatory agencies such as
522:
other fluids) are collected at various time points and analyzed to acquire information on how the drug is processed within the body. The dose is subsequently escalated for further groups, up to a predetermined level.
42:
45:
44:
40:
39:
46:
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3391:
3321:
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Across all trial phases, the main expenses for clinical trials were administrative staff (about 20% of the total), clinical procedures (about 19%), and clinical monitoring of the subjects (about 11%).
3406:
43:
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3356:
687:
of hospitalized people with severe COVID-19 infection, each of which applies adaptive designs to rapidly alter trial parameters as results from the experimental therapeutic strategies emerge.
3242:
736:
In the early 21st century, a typical Phase I trial conducted at a single clinic in the United States ranged from $ 1.4 million for pain or anesthesia studies to $ 6.6 million for
418:
parameters in humans to take forward into further development. They enable go/no-go decisions to be based on relevant human models instead of relying on sometimes inconsistent animal data.
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trial or drug monitoring trial to assure long-term safety and effectiveness of the drug, vaccine, device or diagnostic test. Phase IV trials involve the safety surveillance (
505:
side effects, and the pharmacokinetic data are roughly in line with predicted safe values, the dose is escalated, and a new group of subjects is then given a higher dose.
530:
A short trial designed to investigate any differences in absorption of the drug by the body, caused by eating before the drug is given. These studies are usually run as a
3316:
3291:
3055:
81:, then expand to many study participants (potentially tens of thousands) to determine if the treatment is effective. Clinical research is conducted on drug candidates,
3281:
1699:(PoS) for industry-sponsored vaccine development programs is 39.6%... In contrast, non-industry-sponsored vaccine development programs have an overall PoS of only 6.8%
622:
This phase is designed to assess the effectiveness of the new intervention and, thereby, its value in clinical practice. Phase III studies are randomized controlled
3386:
1093:
3381:
2203:
1408:
810:
The entire process of developing a drug from preclinical research to marketing can take approximately 12 to 18 years and often costs well over $ 1 billion.
3425:
2092:
3346:
3331:
2243:
2238:
1396:
1375:
390:
3266:
3257:
3237:
41:
3247:
337:
Before clinical trials are undertaken for a candidate drug, vaccine, medical device, or diagnostic assay, the product candidate is tested extensively in
2005:
477:
Phase I trials most often include healthy volunteers. However, there are some circumstances when clinical patients are used, such as patients who have
2635:
755:
may cost as low as $ 11 million, whereas a pain or anesthesia Phase III trial may cost as much as $ 53 million. An analysis of Phase III
3306:
3301:
559:
Phase II studies are sometimes divided into Phase IIa and Phase IIb. There is no formal definition for these two sub-categories, but generally:
2253:
3376:
3162:
3106:
3034:
1437:
1289:
1261:
2640:
3366:
722:
A 2010 review found about 50% of drug candidates either fail during the Phase III trial or are rejected by the national regulatory agency.
767:
over 2015–16 showed that the median cost was $ 19 million, but some trials involving thousands of subjects may cost 100 times more.
2672:
2355:
2208:
3082:
2424:
2394:
2027:
880:
655:
Most drugs undergoing Phase III clinical trials can be marketed under FDA norms with proper recommendations and guidelines through a
2494:
1330:
641:
377:
information. Such tests assist the developer to decide whether a drug candidate has scientific merit for further development as an
3061:
2036:
1429:
2645:
566:
Phase IIb studies determine how well the drug works in subjects at a given dose to assess efficacy ('proof of concept' studies).
3456:
2682:
2650:
2479:
2429:
2740:
1033:"Feeding and Bleeding: The Institutional Banalization of Risk to Healthy Volunteers in Phase I Pharmaceutical Clinical Trials"
844:
3451:
2350:
440:
866:
1894:"Estimated costs of pivotal trials for novel therapeutic agents approved by the US Food and Drug Administration, 2015–2016"
1115:
2538:
2248:
1607:
887:
764:
579:, demonstrating a drug's safety and activity in a selected group of participants. Other Phase II trials are designed as
563:
Phase IIa studies are usually pilot studies designed to find an optimal dose and assess safety ('dose finding' studies).
580:
302:
269:
Determines whether drug can have any efficacy; at this point, the drug is not presumed to have any therapeutic effect
982:
Burt, Tal; Young, Graeme; Lee, Wooin; Kusuhara, Hiroyuki; Langer, Oliver; Rowland, Malcolm; Sugiyama, Yuichi (2020).
489:
application to the FDA detailing the preliminary data on the drug gathered from cellular models and animal studies.
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2102:
2085:
779:
1221:
3155:
2710:
1404:
669:
645:
50:
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731:
486:
444:
394:
378:
3200:
3111:
3044:
3025:
2821:
2793:
2755:
2750:
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2258:
909:
427:
338:
332:
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are the most expensive, time-consuming and difficult trials to design and run, especially in therapies for
3092:
3021:
2020:
1696:
1656:"Estimating probabilities of success of vaccine and other anti-infective therapeutic development programs"
1530:
Pallmann P, Bedding AW, Choodari-Oskooei B, Dimairo M, Flight L, Hampson LV, et al. (February 2018).
700:
587:/standard treatment. Randomized Phase II trials have far fewer patients than randomized Phase III trials.
510:
189:
78:
3087:
2921:
2916:
2372:
2318:
2228:
426:
Phase I trials were formerly referred to as "first-in-man studies" but the field generally moved to the
397:(IND) Studies, but now generally adopted as standard practice. Phase 0 trials are also known as human
3148:
2970:
2911:
2702:
2345:
2223:
2174:
2141:
2075:
656:
451:
389:
Phase 0 is a designation for optional exploratory trials, originally introduced by the United States
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2859:
2745:
2511:
2506:
2457:
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2128:
2080:
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Once a dose or range of doses is determined, the next goal is to evaluate whether the drug has any
62:
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1814:
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964:
712:
628:
1165:
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studies. Main expense drivers were operating and clinical monitoring costs of the Phase I site.
293:
Determines a drug's therapeutic effect; at this point, the drug is presumed to have some effect
703:
ranges from 7% for non-industry-sponsored candidates to 40% for industry-sponsored candidates.
3049:
3016:
2995:
2849:
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2580:
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2013:
1991:
1923:
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1806:
1757:
1739:
1563:
1484:
1433:
1285:
1257:
1210:
1131:"Is There a Clinical Future for IDO1 Inhibitors After the Failure of Epacadostat in Melanoma?"
1062:
1013:
1005:
956:
783:
623:
455:
90:
66:
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1981:
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402:
374:
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1918:
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1422:
1371:
1308:
1205:
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1032:
683:
471:
432:
362:
185:
86:
31:
984:"Phase 0/microdosing approaches: time for mainstream application in drug development?"
951:
934:
719:, especially in cancer studies, were more successful than those not using biomarkers.
3440:
3000:
2985:
2955:
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2568:
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2558:
2553:
2462:
2308:
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1400:
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502:
103:
1909:
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1818:
1503:"Adaptive Designs for Clinical Trials of Drugs and Biologics: Guidance for Industry"
968:
3077:
2720:
2615:
2548:
2489:
2313:
2169:
2060:
2040:
1769:
1734:
1582:
1532:"Adaptive designs in clinical trials: why use them, and how to run and report them"
795:
791:
467:
352:
227:
1470:
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2864:
2854:
2715:
2521:
2516:
2434:
2409:
2377:
2303:
2165:
2056:
2048:
1970:"Estimating the cost of new drug development: is it really 802 million dollars?"
752:
576:
398:
365:) experiments using wide-ranging doses of the study agent to obtain preliminary
74:
1188:
2990:
2965:
2655:
2605:
1672:
1548:
1000:
983:
881:"Exploratory IND Studies, Guidance for Industry, Investigators, and Reviewers"
745:
1986:
1969:
1861:
1844:
1743:
1048:
1009:
278:
Testing of drug on participants to assess efficacy, effectiveness and safety
17:
3039:
2610:
2483:
2052:
1663:
799:
716:
348:
1995:
1927:
1870:
1810:
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1567:
1502:
1488:
1214:
1066:
1017:
960:
401:
studies and are designed to speed up the development of promising drugs or
2881:
2874:
2869:
2839:
2595:
2531:
2526:
1845:"Key cost drivers of pharmaceutical clinical trials in the United States"
1682:
370:
366:
343:
169:
151:
147:
2600:
2362:
2044:
1280:
Norfleet E, Gad SC (2009). "Phase I Clinical Trials". In Gad SC (ed.).
584:
535:
357:
239:
20–100 normal healthy volunteers (or cancer patients for cancer drugs)
175:
82:
1311:. Revive, Global Antibiotic Research and Development Partnership. 2023
454:
of the drug have passed. This phase is designed to assess the safety (
65:
to obtain sufficient evidence for a process considered effective as a
2903:
2888:
2179:
1372:"Guidance for Institutional Review Boards and Clinical Investigators"
1801:
1784:
534:, with volunteers being given two identical doses of the drug while
450:
The subject who receives the drug is usually observed until several
254:
Testing of drug on participants to assess efficacy and side effects
1954:
1718:"Estimation of clinical trial success rates and related parameters"
2898:
2783:
2389:
2323:
36:
1633:
583:, where some patients receive the drug/device and others receive
2198:
1424:
Pharmacotherapeutics for
Advanced Practice: A Practical Approach
3144:
2009:
1455:"Phase II trials in drug development and adaptive trial design"
869:. BIO, Informa Pharma Intelligence, and QLS Advisors. Feb 2021.
3140:
1941:
Holland J (2013). "Fixing a broken drug development process".
204:; particularly oral bioavailability and half-life of the drug
61:
are the stages in which scientists conduct experiments with a
1892:
Moore TJ, Zhang H, Anderson G, Alexander GC (November 2018).
485:
Before beginning a Phase I trial, the sponsor must submit an
1785:"Trial watch: phase III and submission failures: 2007–2010"
1716:
Wong, Chi Heem; Siah, Kien Wei; Lo, Andrew W (2018-01-31).
3352:
Nucleoside and nucleotide reverse-transcriptase inhibitors
1621:
data, in order to find the best treatment for our patients
867:"New Clinical Development Success Rates 2011–2020 Report"
1843:
Sertkaya A, Wong HH, Jessup A, Beleche T (April 2016).
245:
Determines whether drug is safe to check for efficacy.
1608:"Launch of a European clinical trial against COVID-19"
3297:
Dual serotonin and norepinephrine reuptake inhibitors
1508:. U.S. Food and Drug Administration. 1 November 2019
1331:"New drugs failing Phase II and III clinical trials"
3223:
3178:
3070:
3009:
2941:
2832:
2804:
2771:
2445:
2276:
2269:
2188:
2116:
2068:
1421:
1189:"The myth of equipoise in phase 1 clinical trials"
1168:. US Food and Drug Administration. 14 October 2016
1129:Van den Eynde BJ, van Baren N, Baurain JF (2020).
935:"Phase 0 trials: a platform for drug development?"
3056:Cedillo v. Secretary of Health and Human Services
847:. US Food and Drug Administration. 4 January 2018
146:Testing of drug in non-human subjects to gather
3342:Non-nucleoside reverse-transcriptase inhibitors
233:Often subtherapeutic, but with ascending doses
1345:"Clinical Development Success Rates 2006–2015"
443:(CROs) who conduct these studies on behalf of
3156:
2021:
263:100–300 participants with a specific disease
73:, the clinical phases start with testing for
8:
501:particular dose. If they do not exhibit any
1525:
1523:
466:of a drug. Phase I trials normally include
284:Clinical researcher and personal physician
3163:
3149:
3141:
2273:
2028:
2014:
2006:
1395:The regulatory authority in the US is the
715:were 33% successful. Trials using disease
314:Anyone seeking treatment from a physician
192:and other human tissues may also be used.
27:Clinical trial stages using human subjects
1985:
1917:
1860:
1800:
1751:
1733:
1681:
1671:
1557:
1547:
1478:
1247:
1245:
1243:
1241:
1239:
1237:
1235:
1233:
1231:
1204:
1146:
1096:. American Cancer Society. 18 August 2020
1056:
999:
950:
287:300–3,000 people with a specific disease
1303:
1301:
1252:DeMets D, Friedman L, Furberg C (2010).
1118:. National Cancer Institute. 2011-02-02.
839:
837:
835:
833:
831:
829:
827:
825:
823:
112:
30:For broader coverage of this topic, see
3302:Selective serotonin reuptake inhibitors
1711:
1709:
1707:
1587:Technology News: Science and Enterprise
1275:
1273:
1148:10.1146/annurev-cancerbio-030419-033635
1037:Science, Technology, & Human Values
819:
492:Phase I trials can be further divided:
1838:
1836:
1834:
1832:
1830:
1828:
1583:"WHO beginning Covid-19 therapy trial"
1409:Ministry of Health, Labour and Welfare
1284:. John Wiley & Sons. p. 247.
1160:
1158:
1094:"Types and phases of clinical trials"
1088:
1086:
1084:
1082:
1080:
1078:
1076:
575:Some Phase II trials are designed as
7:
1654:Lo A, Siah K, Wong C (14 May 2020).
1459:JACC. Basic to Translational Science
778:A Phase IV trial is also known as a
106:, such as "Phase I" clinical trial.
1943:Journal of Commercial Biotechnology
910:"What is a Phase 0 Clinical Trial?"
410:(what the body does to the drugs).
393:(FDA) 2006 Guidance on Exploratory
3392:Bcr-Abl tyrosine-kinase inhibitors
3083:Eradication of infectious diseases
2840:Androvax (androstenedione albumin)
1420:Arcangelo VP, Peterson AM (2005).
794:(brand names Baycol and Lipobay),
25:
3407:Neurokinin 1 receptor antagonists
3282:Dipeptidyl peptidase-4 inhibitors
2673:Respiratory syncytial virus (RSV)
1430:Lippincott Williams & Wilkins
509:drug is said to have reached the
447:or other research investigators.
230:on healthy volunteers for safety
114:Summary of clinical trial phases
3397:Cannabinoid receptor antagonists
3062:Alternative vaccination schedule
2037:Artificial induction of immunity
908:Mandal, Ananya (13 March 2023).
3226:and development of drug classes
1910:10.1001/jamainternmed.2018.3931
1254:Fundamentals of Clinical Trials
1135:Annual Review of Cancer Biology
131:Typical number of participants
3123:
2894:Ovandrotone albumin (Fecundin)
1968:Adams CP, Brantner VV (2006).
1789:Nature Reviews. Drug Discovery
1783:Arrowsmith J (February 2011).
1662:(Special Issue 1 – COVID-19).
845:"The drug development process"
441:contract research organization
391:Food and Drug Administration's
53:video on clinical trial phases
1:
3243:Angiotensin receptor blockers
2430:Group B streptococcal disease
2249:Vaccines for Children Program
1403:; in the European Union, the
988:Nature Reviews Drug Discovery
952:10.1016/S0140-6736(09)61309-X
788:interactions with other drugs
1735:10.1093/biostatistics/kxx069
1695:we can see that the overall
1471:10.1016/j.jacbts.2019.02.005
1397:Food and Drug Administration
1376:Food and Drug Administration
1193:Medscape Journal of Medicine
888:Food and Drug Administration
765:Food and Drug Administration
581:randomized controlled trials
3421:Melatonin receptor agonists
3372:Thalidomide and its analogs
3327:Memantine and related drugs
3277:Cyclooxygenase 2 inhibitors
1660:Harvard Data Science Review
1453:Van Norman GA (June 2019).
1333:. MedCity News. 2011-06-02.
1166:"Step 3. Clinical research"
303:Post marketing surveillance
218:Often skipped for Phase I.
59:phases of clinical research
3473:
3287:Direct thrombin inhibitors
3224:Case studies of discovery
1256:(4th ed.). Springer.
780:postmarketing surveillance
729:
330:
320:Monitor long-term effects
29:
3402:CCR5 receptor antagonists
3101:
1673:10.1162/99608f92.e0c150e8
1581:Kotok A (19 March 2020).
1549:10.1186/s12916-018-1017-7
1405:European Medicines Agency
1309:"Phase 1, 2, 3, 4 trials"
1001:10.1038/s41573-020-0080-x
670:World Health Organization
600:Efficacy vs effectiveness
51:National Cancer Institute
3337:Neuraminidase inhibitors
2425:Clostridioides difficile
1987:10.1377/hlthaff.25.2.420
1862:10.1177/1740774515625964
1282:Clinical Trials Handbook
1049:10.1177/0162243914554838
1031:Fisher JA (March 2015).
933:The Lancet (July 2009).
732:Cost of drug development
726:Cost of trials by phases
487:Investigational New Drug
445:pharmaceutical companies
395:Investigational New Drug
379:investigational new drug
3312:HIV-protease inhibitors
3233:5α-Reductase inhibitors
2683:Tick-borne encephalitis
1610:. INSERM. 22 March 2020
711:drugs and vaccines for
538:, and after being fed.
428:gender-neutral language
341:. Such studies involve
333:Preclinical development
190:immortalized cell lines
3457:Life sciences industry
3362:Proton pump inhibitors
3093:List of vaccine topics
2093:Mathematical modelling
1898:JAMA Internal Medicine
1697:probability of success
701:probability of success
591:Example: cancer design
511:maximum tolerated dose
207:Small, subtherapeutic
164:Scientific researcher
54:
3452:Design of experiments
3088:Vaccinate Your Family
2539:Japanese encephalitis
1222:registration required
751:Phase III trials for
406:data on the agent's
49:
3317:Integrase inhibitors
3292:Direct Xa inhibitors
2971:John Franklin Enders
1407:; and in Japan, the
657:New Drug Application
260:Clinical researcher
236:Clinical researcher
210:Clinical researcher
184:Includes testing in
2157:Virus-like particle
2081:Vaccine ingredients
713:infectious diseases
548:biological activity
339:preclinical studies
327:Preclinical studies
311:Personal physician
167:No human subjects,
115:
63:health intervention
3387:Tubulin inhibitors
3128:Never to phase III
2927:Hexavalent vaccine
2741:Epstein–Barr virus
2636:Oxford–AstraZeneca
2329:NmVac4-A/C/Y/W-135
1187:Shamoo AE (2008).
699:For vaccines, the
648:(European Union).
624:multicenter trials
113:
55:
3447:Clinical research
3434:
3433:
3382:TRPV1 antagonists
3322:Lipase inhibitors
3138:
3137:
3050:Vaccines and SIDS
2937:
2936:
2711:Hepatitis A and B
2687:Varicella zoster
2149:Subunit/component
1904:(11): 1451–1457.
1439:978-0-7817-5784-3
1291:978-0-470-46635-3
1263:978-1-4419-1585-6
784:pharmacovigilance
458:), tolerability,
456:pharmacovigilance
324:
323:
308:Therapeutic dose
281:Therapeutic dose
257:Therapeutic dose
91:diagnostic assays
67:medical treatment
47:
16:(Redirected from
3464:
3426:Renin inhibitors
3272:c-Met inhibitors
3196:Drug development
3165:
3158:
3151:
3142:
3029:MMR autism fraud
2976:Maurice Hilleman
2961:Hilary Koprowski
2274:
2030:
2023:
2016:
2007:
2000:
1999:
1989:
1965:
1959:
1958:
1938:
1932:
1931:
1921:
1889:
1883:
1882:
1864:
1840:
1823:
1822:
1804:
1780:
1774:
1773:
1755:
1737:
1713:
1702:
1701:
1692:
1690:
1685:
1675:
1651:
1645:
1644:
1642:
1640:
1634:"RECOVERY Trial"
1630:
1624:
1623:
1617:
1615:
1604:
1598:
1597:
1595:
1593:
1578:
1572:
1571:
1561:
1551:
1527:
1518:
1517:
1515:
1513:
1507:
1499:
1493:
1492:
1482:
1450:
1444:
1443:
1427:
1417:
1411:
1393:
1387:
1386:
1384:
1383:
1368:
1362:
1361:
1359:
1358:
1349:
1341:
1335:
1334:
1327:
1321:
1320:
1318:
1316:
1305:
1296:
1295:
1277:
1268:
1267:
1249:
1226:
1225:
1218:
1208:
1184:
1178:
1177:
1175:
1173:
1162:
1153:
1152:
1150:
1126:
1120:
1119:
1116:"NCI Dictionary"
1112:
1106:
1105:
1103:
1101:
1090:
1071:
1070:
1060:
1028:
1022:
1021:
1003:
979:
973:
972:
954:
930:
924:
923:
921:
920:
905:
899:
898:
896:
895:
885:
877:
871:
870:
863:
857:
856:
854:
852:
841:
738:immunomodulation
674:Solidarity trial
464:pharmacodynamics
460:pharmacokinetics
408:pharmacokinetics
299:
275:
251:
224:
202:Pharmacokinetics
198:
143:
128:Patient monitor
116:
85:candidates, new
71:drug development
48:
21:
3472:
3471:
3467:
3466:
3465:
3463:
3462:
3461:
3437:
3436:
3435:
3430:
3415:
3357:PDE5 inhibitors
3347:NS5A inhibitors
3332:mTOR inhibitors
3261:
3225:
3219:
3179:Steps in design
3174:
3169:
3139:
3134:
3133:
3118:Clinical trials
3097:
3066:
3005:
2981:Stanley Plotkin
2943:
2933:
2845:Cancer vaccines
2828:
2822:Schistosomiasis
2800:
2794:Trypanosomiasis
2767:
2731:Cytomegalovirus
2641:Pfizer–BioNTech
2441:
2265:
2214:Vaccine wastage
2184:
2112:
2064:
2034:
2004:
2003:
1967:
1966:
1962:
1940:
1939:
1935:
1891:
1890:
1886:
1849:Clinical Trials
1842:
1841:
1826:
1802:10.1038/nrd3375
1782:
1781:
1777:
1715:
1714:
1705:
1688:
1686:
1653:
1652:
1648:
1638:
1636:
1632:
1631:
1627:
1613:
1611:
1606:
1605:
1601:
1591:
1589:
1580:
1579:
1575:
1529:
1528:
1521:
1511:
1509:
1505:
1501:
1500:
1496:
1452:
1451:
1447:
1440:
1419:
1418:
1414:
1394:
1390:
1381:
1379:
1370:
1369:
1365:
1356:
1354:
1347:
1343:
1342:
1338:
1329:
1328:
1324:
1314:
1312:
1307:
1306:
1299:
1292:
1279:
1278:
1271:
1264:
1251:
1250:
1229:
1219:
1186:
1185:
1181:
1171:
1169:
1164:
1163:
1156:
1128:
1127:
1123:
1114:
1113:
1109:
1099:
1097:
1092:
1091:
1074:
1030:
1029:
1025:
994:(11): 801–818.
981:
980:
976:
932:
931:
927:
918:
916:
907:
906:
902:
893:
891:
883:
879:
878:
874:
865:
864:
860:
850:
848:
843:
842:
821:
816:
808:
776:
734:
728:
697:
679:Discovery trial
665:
663:Adaptive design
620:
611:
602:
593:
573:
553:Genetic testing
544:
532:crossover study
528:
519:
498:
424:
416:pharmacokinetic
387:
375:pharmacokinetic
335:
329:
186:model organisms
156:pharmacokinetic
99:
87:medical devices
37:
35:
28:
23:
22:
15:
12:
11:
5:
3470:
3468:
3460:
3459:
3454:
3449:
3439:
3438:
3432:
3431:
3429:
3428:
3423:
3418:
3413:
3409:
3404:
3399:
3394:
3389:
3384:
3379:
3374:
3369:
3364:
3359:
3354:
3349:
3344:
3339:
3334:
3329:
3324:
3319:
3314:
3309:
3304:
3299:
3294:
3289:
3284:
3279:
3274:
3269:
3267:Cephalosporins
3264:
3259:
3255:
3250:
3245:
3240:
3238:ACE inhibitors
3235:
3229:
3227:
3221:
3220:
3218:
3217:
3216:
3215:
3214:
3213:
3203:
3193:
3188:
3186:Drug discovery
3182:
3180:
3176:
3175:
3170:
3168:
3167:
3160:
3153:
3145:
3136:
3135:
3132:
3131:
3130:
3129:
3126:
3115:
3109:
3103:
3102:
3099:
3098:
3096:
3095:
3090:
3085:
3080:
3074:
3072:
3068:
3067:
3065:
3064:
3059:
3052:
3047:
3042:
3037:
3032:
3019:
3013:
3011:
3007:
3006:
3004:
3003:
2998:
2996:Katalin KarikĂł
2993:
2988:
2983:
2978:
2973:
2968:
2963:
2958:
2953:
2947:
2945:
2939:
2938:
2935:
2934:
2932:
2931:
2930:
2929:
2924:
2919:
2914:
2906:
2901:
2896:
2891:
2886:
2885:
2884:
2879:
2878:
2877:
2872:
2862:
2857:
2852:
2842:
2836:
2834:
2830:
2829:
2827:
2826:
2825:
2824:
2819:
2810:
2808:
2802:
2801:
2799:
2798:
2797:
2796:
2788:
2787:
2786:
2775:
2773:
2769:
2768:
2766:
2765:
2764:
2763:
2758:
2753:
2751:Herpes simplex
2748:
2743:
2738:
2733:
2725:
2724:
2723:
2718:
2713:
2705:
2700:
2699:
2698:
2693:
2685:
2680:
2675:
2670:
2669:
2668:
2663:
2658:
2653:
2651:Sinopharm BIBP
2648:
2643:
2638:
2633:
2628:
2623:
2618:
2613:
2608:
2603:
2601:Bharat Biotech
2598:
2588:
2583:
2578:
2573:
2572:
2571:
2566:
2556:
2551:
2546:
2541:
2536:
2535:
2534:
2529:
2519:
2514:
2509:
2504:
2499:
2498:
2497:
2492:
2487:
2472:
2471:
2470:
2460:
2455:
2449:
2447:
2443:
2442:
2440:
2439:
2438:
2437:
2432:
2427:
2419:
2418:
2417:
2412:
2404:
2399:
2398:
2397:
2392:
2382:
2381:
2380:
2370:
2365:
2360:
2359:
2358:
2353:
2343:
2338:
2333:
2332:
2331:
2326:
2316:
2311:
2306:
2301:
2296:
2291:
2286:
2280:
2278:
2271:
2267:
2266:
2264:
2263:
2262:
2261:
2256:
2251:
2246:
2241:
2233:
2232:
2231:
2229:Vaccine injury
2226:
2221:
2216:
2211:
2206:
2201:
2192:
2190:
2189:Administration
2186:
2185:
2183:
2182:
2177:
2172:
2163:
2146:
2145:
2144:
2139:
2131:
2126:
2120:
2118:
2114:
2113:
2111:
2110:
2105:
2100:
2095:
2090:
2089:
2088:
2078:
2072:
2070:
2066:
2065:
2035:
2033:
2032:
2025:
2018:
2010:
2002:
2001:
1974:Health Affairs
1960:
1955:10.5912/jcb588
1933:
1884:
1824:
1775:
1728:(2): 273–286.
1703:
1646:
1625:
1599:
1573:
1519:
1494:
1465:(3): 428–437.
1445:
1438:
1412:
1388:
1363:
1336:
1322:
1297:
1290:
1269:
1262:
1227:
1179:
1154:
1121:
1107:
1072:
1043:(2): 199–226.
1023:
974:
925:
900:
890:. January 2006
872:
858:
818:
817:
815:
812:
807:
804:
798:(Rezulin) and
775:
772:
761:drug approvals
759:leading to 59
757:pivotal trials
727:
724:
696:
693:
684:RECOVERY Trial
664:
661:
619:
616:
610:
607:
601:
598:
592:
589:
572:
569:
568:
567:
564:
543:
540:
527:
524:
518:
515:
497:
494:
472:animal testing
433:selection bias
423:
420:
403:imaging agents
386:
383:
331:Main article:
328:
325:
322:
321:
318:
315:
312:
309:
306:
300:
295:
294:
291:
288:
285:
282:
279:
276:
271:
270:
267:
266:Approx. 28.9%
264:
261:
258:
255:
252:
247:
246:
243:
240:
237:
234:
231:
225:
220:
219:
216:
214:
211:
208:
205:
199:
194:
193:
182:
180:
165:
162:
159:
144:
139:
138:
135:
132:
129:
126:
123:
120:
98:
95:
79:human subjects
32:Clinical trial
26:
24:
14:
13:
10:
9:
6:
4:
3:
2:
3469:
3458:
3455:
3453:
3450:
3448:
3445:
3444:
3442:
3427:
3424:
3422:
3419:
3417:
3410:
3408:
3405:
3403:
3400:
3398:
3395:
3393:
3390:
3388:
3385:
3383:
3380:
3378:
3375:
3373:
3370:
3368:
3365:
3363:
3360:
3358:
3355:
3353:
3350:
3348:
3345:
3343:
3340:
3338:
3335:
3333:
3330:
3328:
3325:
3323:
3320:
3318:
3315:
3313:
3310:
3308:
3305:
3303:
3300:
3298:
3295:
3293:
3290:
3288:
3285:
3283:
3280:
3278:
3275:
3273:
3270:
3268:
3265:
3263:
3256:
3254:
3253:Beta-blockers
3251:
3249:
3248:Antiandrogens
3246:
3244:
3241:
3239:
3236:
3234:
3231:
3230:
3228:
3222:
3212:
3209:
3208:
3207:
3204:
3202:
3199:
3198:
3197:
3194:
3192:
3189:
3187:
3184:
3183:
3181:
3177:
3173:
3166:
3161:
3159:
3154:
3152:
3147:
3146:
3143:
3127:
3125:
3122:
3121:
3119:
3116:
3113:
3110:
3108:
3105:
3104:
3100:
3094:
3091:
3089:
3086:
3084:
3081:
3079:
3076:
3075:
3073:
3069:
3063:
3060:
3058:
3057:
3053:
3051:
3048:
3046:
3043:
3041:
3038:
3036:
3033:
3030:
3028:
3023:
3020:
3018:
3015:
3014:
3012:
3008:
3002:
3001:Drew Weissman
2999:
2997:
2994:
2992:
2989:
2987:
2986:H. Fred Clark
2984:
2982:
2979:
2977:
2974:
2972:
2969:
2967:
2964:
2962:
2959:
2957:
2956:Louis Pasteur
2954:
2952:
2951:Edward Jenner
2949:
2948:
2946:
2940:
2928:
2925:
2923:
2922:DTwP-HepB-Hib
2920:
2918:
2917:DTaP-IPV-HepB
2915:
2913:
2910:
2909:
2908:combination:
2907:
2905:
2902:
2900:
2897:
2895:
2892:
2890:
2887:
2883:
2880:
2876:
2873:
2871:
2868:
2867:
2866:
2863:
2861:
2858:
2856:
2853:
2851:
2848:
2847:
2846:
2843:
2841:
2838:
2837:
2835:
2831:
2823:
2820:
2818:
2815:
2814:
2812:
2811:
2809:
2807:
2806:Helminthiasis
2803:
2795:
2792:
2791:
2789:
2785:
2782:
2781:
2780:
2777:
2776:
2774:
2770:
2762:
2759:
2757:
2754:
2752:
2749:
2747:
2744:
2742:
2739:
2737:
2734:
2732:
2729:
2728:
2726:
2722:
2719:
2717:
2714:
2712:
2709:
2708:
2707:combination:
2706:
2704:
2701:
2697:
2694:
2692:
2689:
2688:
2686:
2684:
2681:
2679:
2676:
2674:
2671:
2667:
2664:
2662:
2659:
2657:
2654:
2652:
2649:
2647:
2644:
2642:
2639:
2637:
2634:
2632:
2629:
2627:
2624:
2622:
2619:
2617:
2614:
2612:
2609:
2607:
2604:
2602:
2599:
2597:
2594:
2593:
2592:
2589:
2587:
2584:
2582:
2579:
2577:
2574:
2570:
2567:
2565:
2562:
2561:
2560:
2557:
2555:
2552:
2550:
2547:
2545:
2542:
2540:
2537:
2533:
2530:
2528:
2525:
2524:
2523:
2520:
2518:
2515:
2513:
2510:
2508:
2505:
2503:
2500:
2496:
2493:
2491:
2488:
2485:
2481:
2478:
2477:
2476:
2473:
2469:
2466:
2465:
2464:
2461:
2459:
2456:
2454:
2451:
2450:
2448:
2444:
2436:
2433:
2431:
2428:
2426:
2423:
2422:
2420:
2416:
2413:
2411:
2410:DPT/DTwP/DTaP
2408:
2407:
2406:combination:
2405:
2403:
2400:
2396:
2393:
2391:
2388:
2387:
2386:
2383:
2379:
2376:
2375:
2374:
2371:
2369:
2366:
2364:
2361:
2357:
2354:
2352:
2349:
2348:
2347:
2344:
2342:
2339:
2337:
2334:
2330:
2327:
2325:
2322:
2321:
2320:
2319:Meningococcus
2317:
2315:
2312:
2310:
2309:Leptospirosis
2307:
2305:
2302:
2300:
2297:
2295:
2292:
2290:
2287:
2285:
2282:
2281:
2279:
2275:
2272:
2268:
2260:
2257:
2255:
2252:
2250:
2247:
2245:
2244:Vaccine court
2242:
2240:
2237:
2236:
2234:
2230:
2227:
2225:
2222:
2220:
2217:
2215:
2212:
2210:
2207:
2205:
2202:
2200:
2199:GAVI Alliance
2197:
2196:
2194:
2193:
2191:
2187:
2181:
2178:
2176:
2173:
2171:
2167:
2164:
2162:
2158:
2154:
2150:
2147:
2143:
2140:
2138:
2135:
2134:
2132:
2130:
2127:
2125:
2122:
2121:
2119:
2115:
2109:
2106:
2104:
2101:
2099:
2096:
2094:
2091:
2087:
2084:
2083:
2082:
2079:
2077:
2074:
2073:
2071:
2067:
2062:
2058:
2054:
2050:
2046:
2042:
2038:
2031:
2026:
2024:
2019:
2017:
2012:
2011:
2008:
1997:
1993:
1988:
1983:
1979:
1975:
1971:
1964:
1961:
1956:
1952:
1948:
1944:
1937:
1934:
1929:
1925:
1920:
1915:
1911:
1907:
1903:
1899:
1895:
1888:
1885:
1880:
1876:
1872:
1868:
1863:
1858:
1855:(2): 117–26.
1854:
1850:
1846:
1839:
1837:
1835:
1833:
1831:
1829:
1825:
1820:
1816:
1812:
1808:
1803:
1798:
1794:
1790:
1786:
1779:
1776:
1771:
1767:
1763:
1759:
1754:
1749:
1745:
1741:
1736:
1731:
1727:
1723:
1722:Biostatistics
1719:
1712:
1710:
1708:
1704:
1700:
1698:
1684:
1683:1721.1/129805
1679:
1674:
1669:
1665:
1661:
1657:
1650:
1647:
1635:
1629:
1626:
1622:
1609:
1603:
1600:
1588:
1584:
1577:
1574:
1569:
1565:
1560:
1555:
1550:
1545:
1541:
1537:
1533:
1526:
1524:
1520:
1504:
1498:
1495:
1490:
1486:
1481:
1476:
1472:
1468:
1464:
1460:
1456:
1449:
1446:
1441:
1435:
1431:
1426:
1425:
1416:
1413:
1410:
1406:
1402:
1401:Health Canada
1399:; in Canada,
1398:
1392:
1389:
1377:
1373:
1367:
1364:
1353:
1346:
1340:
1337:
1332:
1326:
1323:
1310:
1304:
1302:
1298:
1293:
1287:
1283:
1276:
1274:
1270:
1265:
1259:
1255:
1248:
1246:
1244:
1242:
1240:
1238:
1236:
1234:
1232:
1228:
1223:
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1207:
1202:
1198:
1194:
1190:
1183:
1180:
1167:
1161:
1159:
1155:
1149:
1144:
1140:
1136:
1132:
1125:
1122:
1117:
1111:
1108:
1095:
1089:
1087:
1085:
1083:
1081:
1079:
1077:
1073:
1068:
1064:
1059:
1054:
1050:
1046:
1042:
1038:
1034:
1027:
1024:
1019:
1015:
1011:
1007:
1002:
997:
993:
989:
985:
978:
975:
970:
966:
962:
958:
953:
948:
945:(9685): 176.
944:
940:
936:
929:
926:
915:
911:
904:
901:
889:
882:
876:
873:
868:
862:
859:
846:
840:
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836:
834:
832:
830:
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826:
824:
820:
813:
811:
805:
803:
801:
797:
793:
789:
785:
781:
773:
771:
768:
766:
762:
758:
754:
749:
747:
741:
739:
733:
725:
723:
720:
718:
714:
710:
709:ophthalmology
704:
702:
694:
692:
688:
686:
685:
680:
676:
675:
671:
662:
660:
658:
653:
649:
647:
644:(US), or the
643:
637:
633:
630:
625:
617:
615:
608:
606:
599:
597:
590:
588:
586:
582:
578:
570:
565:
562:
561:
560:
557:
554:
549:
541:
539:
537:
533:
525:
523:
516:
514:
512:
506:
504:
495:
493:
490:
488:
483:
480:
475:
473:
469:
465:
461:
457:
453:
448:
446:
442:
436:
434:
429:
421:
419:
417:
411:
409:
404:
400:
396:
392:
384:
382:
380:
376:
372:
368:
364:
360:
359:
354:
350:
346:
345:
340:
334:
326:
319:
316:
313:
310:
307:
304:
301:
297:
296:
292:
289:
286:
283:
280:
277:
273:
272:
268:
265:
262:
259:
256:
253:
249:
248:
244:
241:
238:
235:
232:
229:
226:
222:
221:
217:
215:
212:
209:
206:
203:
200:
196:
195:
191:
187:
183:
181:
178:
177:
172:
171:
166:
163:
161:Unrestricted
160:
157:
153:
149:
145:
141:
140:
136:
134:Success rate
133:
130:
127:
124:
122:Primary goal
121:
118:
117:
111:
107:
105:
104:Roman numeral
96:
94:
92:
88:
84:
80:
76:
72:
68:
64:
60:
52:
33:
19:
18:Phase 2 trial
3210:
3078:Epidemiology
3054:
3026:
2912:DTaP-IPV/Hib
2703:Yellow fever
2616:EpiVacCorona
2373:Tuberculosis
2346:Pneumococcal
2314:Lyme disease
2142:Heterologous
2041:Immunization
1980:(2): 420–8.
1977:
1973:
1963:
1946:
1942:
1936:
1901:
1897:
1887:
1852:
1848:
1792:
1788:
1778:
1725:
1721:
1694:
1687:. Retrieved
1659:
1649:
1637:. Retrieved
1628:
1619:
1612:. Retrieved
1602:
1590:. Retrieved
1586:
1576:
1539:
1536:BMC Medicine
1535:
1510:. Retrieved
1497:
1462:
1458:
1448:
1423:
1415:
1391:
1380:. Retrieved
1378:. 1999-03-16
1366:
1355:. Retrieved
1351:
1339:
1325:
1313:. Retrieved
1281:
1253:
1196:
1192:
1182:
1170:. Retrieved
1138:
1134:
1124:
1110:
1100:15 September
1098:. Retrieved
1040:
1036:
1026:
991:
987:
977:
942:
938:
928:
917:. Retrieved
914:News-Medical
913:
903:
892:. Retrieved
875:
861:
849:. Retrieved
809:
806:Overall cost
796:troglitazone
792:cerivastatin
777:
769:
750:
742:
735:
721:
705:
698:
695:Success rate
689:
682:
678:
672:
666:
654:
650:
638:
634:
621:
612:
609:Success rate
603:
594:
574:
571:Trial design
558:
545:
529:
520:
507:
499:
491:
484:
476:
468:dose-ranging
449:
437:
425:
412:
388:
363:animal model
356:
353:cell culture
342:
336:
242:Approx. 52%
228:Dose-ranging
174:
168:
158:information
108:
100:
58:
56:
3416:antagonists
3201:Preclinical
3191:Hit to lead
3172:Drug design
3114:from market
3010:Controversy
2944:researchers
2860:Hepatitis B
2746:Hepatitis C
2691:Chicken pox
2517:Hepatitis E
2512:Hepatitis B
2507:Hepatitis A
2458:Chikungunya
2435:Shigellosis
2289:Brucellosis
2175:Therapeutic
2129:Inactivated
2069:Development
2057:Inoculation
2049:Vaccination
1199:(11): 254.
1141:: 241–256.
753:dermatology
677:, European
614:2006–2015.
577:case series
526:Food effect
399:microdosing
142:Preclinical
97:Description
75:drug safety
3441:Categories
3307:Gliflozins
3045:Thiomersal
2991:Paul Offit
2966:Jonas Salk
2942:Inventors/
2813:research:
2790:research:
2727:research:
2656:Skycovione
2646:Sanofi–GSK
2591:SARS-CoV-2
2502:Hantavirus
2468:rVSV-ZEBOV
2453:Adenovirus
2421:research:
2299:Diphtheria
2137:Attenuated
1382:2007-03-27
1357:2018-02-11
1315:24 October
1172:1 February
919:2024-06-28
894:2010-06-15
814:References
763:by the US
746:hematology
730:See also:
717:biomarkers
632:the drug.
452:half-lives
305:in public
213:10 people
89:, and new
3124:Phase III
3112:Withdrawn
3040:Pox party
2850:ALVAC-CEA
2772:Protozoan
2661:Sputnik V
2611:CoronaVac
2581:Rotavirus
2484:Pandemrix
2336:Pertussis
2277:Bacterial
2161:Synthetic
2124:Conjugate
2076:Adjuvants
2053:Infection
1795:(2): 87.
1744:1465-4644
1689:11 August
1664:MIT Press
1542:(1): 29.
1010:1474-1784
851:17 August
802:(Vioxx).
800:rofecoxib
681:, and UK
668:the 2020
618:Phase III
349:test tube
274:Phase III
77:in a few
3377:Triptans
3262:agonists
3206:Clinical
2882:Prostvac
2875:Gardasil
2870:Cervarix
2817:Hookworm
2696:Shingles
2678:Smallpox
2596:Corbevax
2532:Gardasil
2527:Cervarix
2270:Vaccines
2224:Schedule
2195:Global:
2103:Timeline
2045:Vaccines
1996:16522582
1928:30264133
1879:24308679
1871:26908540
1819:39480483
1811:21283095
1762:29394327
1568:29490655
1489:31312766
1215:19099004
1067:25914430
1018:32901140
969:30939770
961:19616703
774:Phase IV
748:trials.
542:Phase II
517:Phase Ib
496:Phase Ia
479:terminal
371:toxicity
367:efficacy
344:in vitro
298:Phase IV
250:Phase II
188:. Human
170:in vitro
152:toxicity
148:efficacy
3367:Statins
3071:Related
3017:General
2779:Malaria
2666:Valneva
2631:Novavax
2626:Moderna
2621:Janssen
2606:CanSino
2586:Rubella
2544:Measles
2415:Td/Tdap
2385:Typhoid
2368:Tetanus
2363:Q fever
2294:Cholera
2284:Anthrax
2153:Peptide
2117:Classes
2098:Storage
1919:6248200
1770:3277297
1753:6409418
1639:17 June
1614:5 April
1592:7 April
1559:5830330
1512:3 April
1480:6609997
1352:bio.org
1206:2605120
1058:4405793
629:chronic
585:placebo
503:adverse
422:Phase I
385:Phase 0
358:in vivo
223:Phase I
197:Phase 0
176:in vivo
83:vaccine
3211:Phases
3107:WHO-EM
3027:Lancet
2904:TA-NIC
2889:NicVAX
2736:Dengue
2576:Rabies
2402:Typhus
2341:Plague
2219:Policy
2180:Toxoid
2108:Trials
1994:
1926:
1916:
1877:
1869:
1817:
1809:
1768:
1760:
1750:
1742:
1566:
1556:
1487:
1477:
1436:
1288:
1260:
1213:
1203:
1065:
1055:
1016:
1008:
967:
959:
939:Lancet
536:fasted
462:, and
355:) and
290:57.8%
137:Notes
119:Phase
69:. For
3035:NCVIA
2899:TA-CD
2833:Other
2784:RTS,S
2564:Sabin
2559:Polio
2554:Mumps
2463:Ebola
2446:Viral
2395:ViCPS
2390:Ty21a
2324:MeNZB
2254:VAERS
2204:NITAG
2133:Live
1875:S2CID
1815:S2CID
1766:S2CID
1506:(PDF)
1348:(PDF)
965:S2CID
884:(PDF)
179:only
125:Dose
3412:5-HT
3258:Beta
2761:Zika
2721:MMRV
2569:Salk
2549:Mpox
2495:LAIV
2490:H5N1
2480:H1N1
2356:PPSV
2239:ACIP
2235:US:
2209:SAGE
2170:mRNA
2086:list
1992:PMID
1924:PMID
1867:PMID
1807:PMID
1758:PMID
1740:ISSN
1691:2020
1641:2020
1616:2020
1594:2020
1564:PMID
1514:2020
1485:PMID
1434:ISBN
1317:2023
1286:ISBN
1258:ISBN
1211:PMID
1174:2017
1102:2020
1063:PMID
1014:PMID
1006:ISSN
957:PMID
853:2020
373:and
317:N/A
173:and
154:and
57:The
3022:MMR
2865:HPV
2855:BCG
2756:HIV
2716:MMR
2522:HPV
2475:Flu
2378:BCG
2351:PCV
2304:Hib
2259:VSD
2166:DNA
2061:J07
1982:doi
1951:doi
1914:PMC
1906:doi
1902:178
1857:doi
1797:doi
1748:PMC
1730:doi
1678:hdl
1668:doi
1554:PMC
1544:doi
1475:PMC
1467:doi
1201:PMC
1143:doi
1053:PMC
1045:doi
996:doi
947:doi
943:374
646:EMA
642:FDA
351:or
3443::
3120::
2168:/
2159:/
2155:/
2151:/
2055:,
2051:,
2047:,
2043::
2039:/
1990:.
1978:25
1976:.
1972:.
1949:.
1947:19
1945:.
1922:.
1912:.
1900:.
1896:.
1873:.
1865:.
1853:13
1851:.
1847:.
1827:^
1813:.
1805:.
1793:10
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1724:.
1720:.
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1538:.
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1350:.
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1133:.
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1041:40
1039:.
1035:.
1012:.
1004:.
992:19
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955:.
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