{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T20:30:38Z","timestamp":1784320238078,"version":"3.55.0"},"reference-count":60,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2022,7,25]],"date-time":"2022-07-25T00:00:00Z","timestamp":1658707200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Tuberculosis (TB), human immunodeficiency virus (HIV), and hepatitis C virus (HCV) share a global presence and propensity to disproportionately affect marginalized populations. However, over recent decades, many fewer drugs have been brought to market for TB than for the others. Although three new anti-TB drugs have been approved in the US or Europe in the last 10 years, uptake of these drugs has been limited. Using case examples of drugs developed recently for TB, HIV, and HCV, we explore possible reasons. We examine the use and effect of regulatory pathways intended to address weak economic incentives in the face of urgent, unmet needs; evaluate the extent of data underpinning authorizations for these indications; document development timelines and evidence available at the time of each approval; consider explanations for observed differences; and discuss the implications for clinical guidelines and use.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods and findings<\/jats:title>\n<jats:p>For each indication, we selected two drugs: one recently approved and one approved between 2012 and 2014, when the first new anti-TB drug from a novel class in more than 40 years received marketing authorization. We calculated time from first published peer-reviewed evidence of activity to date of approval; the number of phase 1, 2, and 3 trials; the number of trial participants randomized to treatment arms containing the drug; and the total number of participants in each trial from the individual drug approval packages. We found that the two TB drugs took longer to gain approval (8.0 and 19.2 years for bedaquiline and pretomanid, respectively) despite availing of special regulatory pathways meant to expedite approval, when compared to the HIV (2.6 years for dolutegravir and 4.7 years for doravirine) and HCV drugs (3.2 and 1.6 years for sofosbuvir and glecaprevir\/pibrentasvir, respectively). Moreover, fewer participants were studied prior to TB drug approvals (380 and 879) than prior to approvals for HIV (1598 and 979) and for HCV (2291 and 2448) drugs.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>The dramatic disparities observed in TB drug development reaffirm the importance of several actions. Increased investment in TB research and development is necessary to rapidly advance drugs through the pipeline. Development plans and partnerships must provide safety and efficacy evidence on combinations and durations that are relevant to real-world use in heterogeneous populations. Reliable, validated surrogate markers of relapse-free cure are essential to decrease the duration and cost of TB treatment trials and increase the confidence and speed with which new regimens can advance. Lastly, regulators and normative bodies must maintain high evidentiary standards for authorization while ensuring timely and broad approval for TB drugs and regimens.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0271102","type":"journal-article","created":{"date-parts":[[2022,7,25]],"date-time":"2022-07-25T17:28:18Z","timestamp":1658770098000},"page":"e0271102","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["Comparing timelines and evidence available to support new TB, HIV, and HCV drug approvals: The same, only different"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8415-133X","authenticated-orcid":true,"given":"Allison","family":"LaHood","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rifat","family":"Rahman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay","family":"McKenna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mike","family":"Frick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3455-658X","authenticated-orcid":true,"given":"Carole D.","family":"Mitnick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,7,25]]},"reference":[{"key":"pone.0271102.ref001","unstructured":"FDA-approved HIV medicines [Internet]. 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