; (2) in clause (i) of subparagraph (B), by inserting before the semicolon , or new effectiveness information ; (3) in subparagraph (C) by striking safety information and inserting safety or new effectiveness information ; and (4) in subparagraph (E) by striking safety information and inserting safety or new effectiveness information . (c) Guidance Not less than one year after the date of enactment of this Act, the Secretary of Health and Human Services shall issue guidance regarding the circumstances under which the Food and Drug Administration may require postmarket studies or clinical trials to assess the potential reduction in effectiveness of a drug and how such reduction in effectiveness could result in a change to the benefits of the drug and the risks to the patient. Such guidance shall also address how the Food and Drug Administration may apply this section and the amendments made thereby with respect to circumstances under which the Food and Drug Administration may require postmarket studies or clinical trials and safety labeling changes related to the use of controlled substances for acute or chronic pain. B Controlled substance provisions 1 More flexibility with respect to medication-Assisted treatment for opioid use disorders 3201. Allowing for more flexibility with respect to medication-assisted treatment for opioid use disorders (a) Conforming applicable number Subclause (II) of section 303(g)(2)(B)(iii) of the Controlled Substances Act ( 21 U.S.C. 823(g)(2)(B)(iii) ) is amended to read as follows: (II) The applicable number is— (aa) 100 if, not sooner than 1 year after the date on which the practitioner submitted the initial notification, the practitioner submits a second notification to the Secretary of the need and intent of the practitioner to treat up to 100 patients; (bb) 100 if the practitioner holds additional credentialing, as defined in section 8.2 of title 42, Code of Federal Regulations (or successor regulations)