NURS 316 I
Unit I1:
Chapter I1:
• Clinical Ipharmacology Iis Ithe Istudy Iof Idrugs Iused Ito Itreat, Idiagnose, Ior Iprevent Ia Idisease.
• Drugs Iare Ichemicals Ithat Iare Iintroduced Iinto Ithe Ibody Iand Iaffect Ithe Ibody’s Ichemical
Iprocesses.
• Drugs Ican Icome Ifrom Inatural Isources Iincluding Iplants, Ifoods, Ianimals, Isalts Iof Iinorganic
Icompounds, Ior Isynthetic Isources.
• Drug IEvaluation
• After Ia Ichemical Ithat Imight Ihave Itherapeutic Ivalue Iis Iidentified, Iit Imust Iundergo Ia Iseries
Iof Iscientific Itests Ito Ievaluate Iits Iactual Itherapeutic Iand Itoxic Ieffects. IThis Iprocess Iis
Itightly Icontrolled Iby Ithe IU.S. IFood Iand IDrug IAdministration I(FDA), IFor Ievery
I100,000 Ichemicals Ithat Iare Iidentified Ias Ibeing Ipotential Idrugs, Ionly Iabout Ifive Iend Iup
Ibeing Imarketed. IBefore Ireceiving Ifinal IFDA Iapproval Ito Ibe Imarketed Ito Ithe Ipublic, Idrugs
Imust Ipass Ithrough Iseveral Istages Iof Idevelopment. IThese Iinclude Ipreclinical Itrials Iand
Iphase II, III, Iand IIII Istudies.
1. Preclinical ITrials
In Ipreclinical Itrials, Ichemicals Ithat Imay Ihave Itherapeutic Ivalue Iare Itested Ion Ilaboratory Ianimals
Ifor Itwo Imain Ipurposes: I(1) Ito Idetermine Iwhether Ithey Ihave Ithe Ipresumed Ieffects Iin Iliving Itissue
Iand I(2) Ito Ievaluate Iany Iadverse Ieffects. IAnimal Itesting Iis Iimportant Ibecause Iunique Ibiological
Idifferences Ican Icause Ivery Idifferent Ireactions Ito Ithe Ichemical.
These Idifferences Ican Ibe Ifound Ionly Iin Iliving Iorganisms, Iso Icomputer-generated ImodelsIalone
are Ioften Iinadequate.
I
At Ithe Iend Iof Ithe Ipreclinical Itrials, Isome Ichemicals Iare Idiscarded Ifor Ithe Ifollowing Ireasons:
• The Ichemical Ilacks Itherapeutic Iactivity Iwhen Iused Iwith Iliving Ianimals.
• The Ichemical Iis Itoo Itoxic Ito Iliving Ianimals Ito Ibe Iworth Ithe Irisk Iof Ideveloping Iinto Ia Idrug.
• The Ichemical Iis Ihighly Iteratogenic I(causing Iadverse Ieffects Ito Ia Ifetus).
• The Isafety Imargins Iare Iso Ismall Ithat Ithe Ichemical Iwould Inot Ibe Iuseful Iin Ithe Iclinical
Isetting.
Some Ichemicals, Ihowever, Iare Ifound Ito Ihave Itherapeutic Ieffects Iand Ireasonable Isafety Imargins.
IThis Imeans Ithat Ithe Ichemicals Iare Itherapeutic Iat Idoses Ithat Iare Ireasonably Idifferent Ifrom Idoses
It hat Icause Itoxic Ieffects. ISuch Ichemicals Iwill Ipass Ithe Ipreclinical Itrials Iand Iadvance Ito Iphase II
Istudies.
2. Phase II IStudies
A Iphase II Istudy Iuses Ihuman Ivolunteers Ito Itest Ithe Idrugs. IThese Istudies Iare Imore Itightly
Icontrolled Ithan Ipreclinical Itrials Iand Iare Iperformed Iby Ispecially Itrained Iclinical Iinvestigators. IThe
Ivolunteers Iare Ifully Iinformed Iof Ipossible Irisks Iand Imay Ibe Ipaid Ifor Itheir Iparticipation. IUsually,
,the Ivolunteers Iare Ihealthy, Iyoung Imen Iand Ioften Iwomen. IWomen Iof Ichildbearing Ipotential Iare
Isometimes Inot Igood Icandidates Ifor Iphase II Istudies Ibecause Ithe Ichemicals Imay Iexert Iunknown
Iand Iharmful Ieffects Ion Ia Iwoman’s Iova, Iand Itoo Imuch Irisk Iis Iinvolved Iin Itaking Ia Idrug Ithat Imight
Idestroy Ior Ialter Ithe Iova. IWomen Ido Inot Imake Inew Iova Iafter Ibirth. IMen Iproduce Isperm Idaily, Iso
Ithere Iis Iless Ipotential Ifor Icomplete Idestruction Ior Ialteration Iof Ithe Isperm. IVolunteers Iwho Ielect Ito
Iparticipate Iin Iphase II Istudies Ihave Ito Ibe Iinformed Iof Ithe Ipotential Irisks Iand Imust Isign Ia Iconsent
Iform Ioutlining Ithe Ipossible Ieffects.
Some Ichemicals Iare Itherapeutic Iin Iother Ianimals Ibut Ihave Ino Ieffects Iin Ihumans. IInvestigators
in Iphase II Istudies Iscrutinize Ithe Idrugs Ibeing Itested Ifor Ieffects Iin Ihumans. IThey Ialso Ilook Ifor
I
Iadverse Ieffects Iand Itoxicity. IAt Ithe Iend Iof Iphase II Istudies, Imany Ichemicals Iare Idropped Ifrom Ithe
Iprocess Ifor Ithe Ifollowing Ireasons:
• They Icause Iunacceptable Iadverse Ieffects.
• They Iare Ihighly Iteratogenic.
• They Iare Itoo Itoxic.
• They Ilack Ievidence Iof Ipotential Itherapeutic Ieffect Iin Ihumans.
Some Ichemicals Imove Ito Ithe Inext Istage Iof Itesting Idespite Iundesirable Ieffects. IFor Iexample, Ithe
Iantihypertensive Idrug Iminoxidil Iwas Ifound Ito Ieffectively Itreat Imalignant Ihypertension, Ibut Iit
Icaused Iunusual Ihair Igrowth Ion Ithe Ipalms Iand Iother Ibody Iareas. IHowever, Ibecause Iit Iwas Iso Imuch
Imore Ieffective Ifor Itreating Imalignant Ihypertension Iat Ithe Itime Iof Iits Idevelopment Ithan Iany Iother
Iantihypertensive Idrug Iand Ibecause Ithe Iundesired Ieffects Iwere Inot Idangerous, Iit Iproceeded Ito
Iphase III Istudies. I(Now, Iits Ihair-growing Ieffect Ihas Ibeen Ichanneled Ifor Itherapeutic Iuse Iinto
Ivarious Itopical Ihair-growth Ipreparations Isuch Ias IRogaine.)
3. Phase III IStudies
A Iphase III Istudy Iallows Iclinical Iinvestigators Ito Itry Iout Ithe Idrug Iin Ipatients Iwho Ihave Ithe
Idisease Ithat Ithe Idrug Iis Idesigned Ito Itreat. IPatients Iare Itold Iabout Ithe Ipossible Ibenefits Iof Ithe Idrug
Iand Iare Iinvited Ito Iparticipate Iin Ithe Istudy. IThose Iwho Iconsent Ito Iparticipate Iare Ifully Iinformed
Iabout Ipossible Irisks Iand Iare Imonitored Ivery Iclosely, Ioften Iat Ino Icharge Ito Ithem, Ito Ievaluate Ithe
Idrug’s Ieffects. IUsually, Iphase III Istudies Iare Iperformed Iat Ivarious Isites Iacross Ithe Icountry—in
Ihospitals, Iclinics, Iand Idoctors’ Ioffices—and Iare Imonitored Iby Irepresentatives Iof Ithe
Ipharmaceutical Icompany Istudying Ithe Idrug. IAt Ithe Iend Iof Iphase III Istudies, Ia Idrug Imay Ibe
Iremoved Ifrom Ifurther Iinvestigation Ifor Ithe Ifollowing Ireasons:
• It Iis Iless Ieffective Ithan Ianticipated.
• It Iis Itoo Itoxic Iwhen Iused Iwith Ipatients.
• It Iproduces Iunacceptable Iadverse Ieffects.
• It Ihas Ia Ilow Ibenefit-to-risk Iratio, Imeaning Ithat Ithe Itherapeutic Ibenefit Iit Iprovides Idoes Inot
Io utweigh Ithe Irisk Iof Ipotential Iadverse Ieffects Ithat Iit Icauses.
• It Iis Ino Imore Ieffective Ithan Iother Idrugs Ialready Ion Ithe Imarket, Imaking Ithe Icost Iof
Icontinued Iresearch Iand Iproduction Iless Iattractive Ito Ithe Idrug Icompany.
A Idrug Ithat Icontinues Ito Ishow Ipromise Ias Ia Itherapeutic Iagent Ireceives Iadditional Iscrutiny IinIphase
IIII Istudies.
,4. Phase IIII IStudies
A Iphase IIII Istudy Iinvolves Iuse Iof Ithe Idrug Iin Ia Ivast Iclinical Imarket. IPrescribers Iare Iinformed Iof
Ia ll Ithe Iknown Ireactions Ito Ithe Idrug Iand Iprecautions Irequired Ifor Iits Isafe Iuse. IPrescribers Iobserve
Ipatients Ivery Iclosely, Imonitoring Ithem Ifor Iany Iadverse Ieffects. IOften, Iprescribers Iask Ipatients Ito
Ikeep Ijournals Iand Irecord Iany Isymptoms Ithey Iexperience. IPrescribers Ithen Ievaluate Ithe Ireported
Ieffects Ito Idetermine Iwhether Ithey Iare Icaused Iby Ithe Idisease Ior Iby Ithe Idrug. IThis Iinformation Iis
Icollected Iby Ithe Idrug Icompany Ithat Iis Ideveloping Ithe Idrug Iand Iis Ishared Iwith Ithe IFDA. IWhen Ia
Idrug Iis Iused Iwidely Iand Iwithin Iuncontrolled Ienvironments, Itotally Iunexpected Iresponses Imay
Ioccur. IA Idrug Ithat Iproduces Iunacceptable Iadverse Ieffects Ior Iunforeseen Ireactions Iis Iusually
Iremoved Ifrom Ifurther Istudy Iby Ithe Idrug Icompany. IIn Isome Icases, Ithe IFDA Imay Ihave Ito Irequest
Ithat Ia Idrug Ibe Iremoved Ifrom Ithe Imarket.
An Iapproved Idrug Iis Igiven Ia Ibrand Iname I(trade Iname) Iby Ithe Ipharmaceutical Icompany Ithat
Ideveloped Iit. IThe Igeneric Iname Iof Ia Idrug Iis Ithe Ioriginal Idesignation Ithat Ithe Idrug Iwas Igiven
Iwhen Ithe Idrug Icompany Iapplied Ifor Ithe Iapproval Iprocess. IChemical Inames Iare Inames Ithat Ireflect
It he Ichemical Istructure Iof Ia Idrug. ISome Idrugs Iare Iknown Iby Iall Ithree Inames. IIt Ican Ibe Iconfusing
Ito Istudy Idrugs Iwhen Iso Imany Idifferent Inames Iare Iused Ifor Ithe Isame Icompound. IIn Ithis Itext, Ithe
Igeneric Iand Ichemical Inames Ialways Iappear Iin Istraight Iprint, Iand Ithe Ibrand Iname Iis Ialways
Icapitalized Iand Iitalicized I(e.g., Iminoxidil I[Rogaine]).
In Iaddition Ito Ithe Idrug Ilag Iissue, Ithere Ialso Iare Iconcerns Iabout Ithe Ihigh Icost Iof Idrug Iapproval. IIn
2013, IForbes IMagazine Idid Ia Istudy Ithat Ifound Ithat Ithe Iestimated Icost Iof Itaking Ia Ichemical Ifrom
I
Idiscovery Ito Imarketing Ias Ia Idrug Iranged Ifrom I$800 Imillion Ito I$5.3 Ibillion. IBecause Iof Ithis Ikind
Iof Ifinancial Iinvestment, Ipharmaceutical Icompanies Iare Iunwilling Ito Irisk Iapproval Iof Ia Idrug Ithat
Imight Icause Iserious Iproblems Iand Iprompt Ilawsuits.
5. Phase IIV IStudies
After Ia Idrug Iis Iapproved Ifor Imarketing, Iit Ienters Ia Iphase Iof Icontinual Ievaluation, Ior Iphase IIV
Istudy. IPrescribers Iand Iall Ihealthcare Iprofessionals Iare Iobligated Ito Ireport Ito Ithe IFDA Iany
Iuntoward Ior Iunexpected Iadverse Ieffects Iassociated Iwith Idrugs Ithey Iare Iusing, Iand Ithe IFDA
Icontinually Ievaluates Ithis Iinformation. ISome Idrugs Icause Iunexpected Ieffects Ithat Iare Inot Iseen
Iuntil Iwide Idistribution Ioccurs. ISometimes, Ithose Ieffects Iare Itherapeutic. IFor Iexample, Ipatients
It aking Ithe Iantiparkinsonism Idrug Iamantadine I(Symmetrel) Iwere Ifound Ito Ihave Ifewer Icases Iof
Iinfluenza Ithan Iother Ipatients, Ileading Ito Ithe Idiscovery Ithat Iamantadine Iis Ian Ieffective Iantiviral
Iagent.
In Iother Iinstances, Ithe Iunexpected Ieffects Iare Idangerous. IIn I1997, Ithe Idiet Idrug
Idexfenfluramine I(Redux) Iwas Iremoved Ifrom Ithe Imarket Ionly Imonths Iafter Iits Irelease Ibecause
Ipatients Itaking Iit Ideveloped Iserious Iheart Iproblems. IIn I2004, Ithe Idrug Icompany IMerck Iwithdrew
Iits Icyclooxygenase-2 I(Cox-2)-specific Inonsteroidal Ianti-inflammatory Idrug Irofecoxib I(Vioxx)
Ifrom Ithe Imarket Iwhen Ipostmarketing Istudies Iseemed Ito Ishow Ia Isignificant Iincrease Iin
Icardiovascular Imortality Iin Ipatients Iwho Iwere Itaking Ithe Idrug. IThese Iproblems Iwere Inot Iseen Iin
Iany Iof Ithe Ipremarketing Istudies Iof Ithe Idrug. IThe Ieffects Iwere Ionly Iseen Iwith Ia Imuch Iwider Iuse Iof
It he Idrug Iafter Iit Ihad Ibeen Imarketed.
Key IPoints
, • The IFDA Icarefully Iregulates Ithe Itesting Iand Iapproval Iof Iall Idrugs Iin Ithis Icountry.
• To Ibe Iapproved Ifor Imarketing, Ia Idrug Imust Ipass Ithrough Ianimal Itesting, Itesting Ion Ihealthy
Ihumans, Iselected Itesting Ion Ipeople Iwith Ithe Idisease Ibeing Itreated, Iand Ithen Ibroad Itesting
on Ipeople Iwith Ithe Idisease Ibeing Itreated.
The IFDA Ihas Iestablished Ifive Icategories Ito Iindicate Ithe Ipotential Ifor Ia Isystemically Iabsorbed
Idrug Ito Icause Ibirth Idefects.
Category IA: IAdequate Istudies Iin Ipregnant Iwomen Ihave Inot Idemonstrated Ia Irisk Ito Ithe Ifetus
Iin Ithe Ifirst Itrimester Iof Ipregnancy, Iand Ithere Iis Ino Ievidence Iof Irisk Iin Ilater Itrimesters.
Category IB: IAnimal Istudies Ihave Inot Idemonstrated Ia Irisk Ito Ithe Ifetus, Ibut Ithere Iare Ino
Iadequate Istudies Iin Ipregnant Iwomen, Ior I animal Istudies Ihave Ishown Ian Iadverse Ieffect, Ibut
Iadequate Istudies Iin Ipregnant Iwomen Ihave Inot Idemonstrated Ia Irisk Ito Ithe Ifetus Iduring Ithe Ifirst
It rimester Iof Ipregnancy, Iand Ithere Iis Ino Ievidence Iof Irisk Iin Ilater Itrimesters.
Category IC: IAnimal Istudies Ihave Ishown Ian Iadverse Ieffect Ion Ithe Ifetus, Ibut Ithere Iare Ino
Iadequate Istudies Iin Ihumans; Ithe Ibenefits Ifrom Ithe Iuse Iof Ithe Idrug Iin Ipregnant Iwomen Imay Ibe
Iacceptable Idespite Iits Ipotential Irisks, Ior Ithere Iare Ino Ianimal Ireproduction Istudies Iand Ino Iadequate
Istudies Iin Ihumans.
Category ID: IThere Iis Ievidence Iof Ihuman Ifetal Irisk, Ibut Ithe Ipotential Ibenefits Ifrom Ithe Iuse Iof
It he Idrug Iin Ipregnant Iwomen Imay Ibe Iacceptable Idespite Iits Ipotential Irisks.
Category IX: IStudies Iin Ianimals Ior Ihumans Idemonstrate Ifetal Iabnormalities Ior Iadverse
Ireactions; Ireports Iindicate Ievidence Iof Ifetal Irisk. IThe Irisk Iof Iuse Iin Ia Ipregnant Iwoman Iclearly
Io utweighs Iany Ipossible Ibenefit.
Regardless Iof Ithe Idesignated Ipregnancy Icategory Ior Ipresumed Isafety, Ino Idrug Ishould Ibe
administered Iduring Ipregnancy Iunless Iit Iis Iclearly Ineeded.
I
The IControlled ISubstances IAct Iof I1970 Iestablished Icategories Ifor Iranking Iof Ithe Iabuse Ipotential
Iof Ivarious Idrugs. IThis Isame Iact Igave Icontrol Iover Ithe Icoding Iof Idrugs Iand Ithe Ienforcement Iof
Ithese Icodes Ito Ithe IFDA Iand Ithe IDrug IEnforcement IAgency I(DEA), Ia Ipart Iof Ithe IU.S. IDepartment
Io f IJustice. IThe IFDA Istudies Ithe Idrugs Iand Idetermines Itheir Iabuse Ipotential; Ithe IDEA Ienforces
Itheir Icontrol. IDrugs Iwith Iabuse Ipotential Iare Icalled Icontrolled Isubstances. IBox I1.2 Icontains
Idescriptions Iof Ieach Icategory Ior Ischedule.
Drug IEnforcement IAgency ISchedules Iof IControlled ISubstances
The IControlled ISubstances IAct Iof I1970 Iregulates Ithe Imanufacturing, Idistribution, Iand Idispensing
Io f Idrugs Ithat Iare Iknown Ito Ihave Iabuse Ipotential. IThe IDEA Iis Iresponsible Ifor Ithe Ienforcement Iof
Ithese Iregulations. IThe Icontrolled Idrugs Iare Idivided Iinto Ifive IDEA Ischedules Ibased Ion Itheir
Ipotential Ifor Iabuse Iand Iphysical Iand Ipsychological Idependence:
Schedule II I(C-I): IHigh Iabuse Ipotential Iand Ino Iaccepted Imedical Iuse I(heroin, Imarijuana, ILSD)
Schedule III I(C-II): IHigh Iabuse Ipotential Iwith Isevere Idependence Iliability I(narcotics,
Ia mphetamines, Iand Ibarbiturates)
Unit I1:
Chapter I1:
• Clinical Ipharmacology Iis Ithe Istudy Iof Idrugs Iused Ito Itreat, Idiagnose, Ior Iprevent Ia Idisease.
• Drugs Iare Ichemicals Ithat Iare Iintroduced Iinto Ithe Ibody Iand Iaffect Ithe Ibody’s Ichemical
Iprocesses.
• Drugs Ican Icome Ifrom Inatural Isources Iincluding Iplants, Ifoods, Ianimals, Isalts Iof Iinorganic
Icompounds, Ior Isynthetic Isources.
• Drug IEvaluation
• After Ia Ichemical Ithat Imight Ihave Itherapeutic Ivalue Iis Iidentified, Iit Imust Iundergo Ia Iseries
Iof Iscientific Itests Ito Ievaluate Iits Iactual Itherapeutic Iand Itoxic Ieffects. IThis Iprocess Iis
Itightly Icontrolled Iby Ithe IU.S. IFood Iand IDrug IAdministration I(FDA), IFor Ievery
I100,000 Ichemicals Ithat Iare Iidentified Ias Ibeing Ipotential Idrugs, Ionly Iabout Ifive Iend Iup
Ibeing Imarketed. IBefore Ireceiving Ifinal IFDA Iapproval Ito Ibe Imarketed Ito Ithe Ipublic, Idrugs
Imust Ipass Ithrough Iseveral Istages Iof Idevelopment. IThese Iinclude Ipreclinical Itrials Iand
Iphase II, III, Iand IIII Istudies.
1. Preclinical ITrials
In Ipreclinical Itrials, Ichemicals Ithat Imay Ihave Itherapeutic Ivalue Iare Itested Ion Ilaboratory Ianimals
Ifor Itwo Imain Ipurposes: I(1) Ito Idetermine Iwhether Ithey Ihave Ithe Ipresumed Ieffects Iin Iliving Itissue
Iand I(2) Ito Ievaluate Iany Iadverse Ieffects. IAnimal Itesting Iis Iimportant Ibecause Iunique Ibiological
Idifferences Ican Icause Ivery Idifferent Ireactions Ito Ithe Ichemical.
These Idifferences Ican Ibe Ifound Ionly Iin Iliving Iorganisms, Iso Icomputer-generated ImodelsIalone
are Ioften Iinadequate.
I
At Ithe Iend Iof Ithe Ipreclinical Itrials, Isome Ichemicals Iare Idiscarded Ifor Ithe Ifollowing Ireasons:
• The Ichemical Ilacks Itherapeutic Iactivity Iwhen Iused Iwith Iliving Ianimals.
• The Ichemical Iis Itoo Itoxic Ito Iliving Ianimals Ito Ibe Iworth Ithe Irisk Iof Ideveloping Iinto Ia Idrug.
• The Ichemical Iis Ihighly Iteratogenic I(causing Iadverse Ieffects Ito Ia Ifetus).
• The Isafety Imargins Iare Iso Ismall Ithat Ithe Ichemical Iwould Inot Ibe Iuseful Iin Ithe Iclinical
Isetting.
Some Ichemicals, Ihowever, Iare Ifound Ito Ihave Itherapeutic Ieffects Iand Ireasonable Isafety Imargins.
IThis Imeans Ithat Ithe Ichemicals Iare Itherapeutic Iat Idoses Ithat Iare Ireasonably Idifferent Ifrom Idoses
It hat Icause Itoxic Ieffects. ISuch Ichemicals Iwill Ipass Ithe Ipreclinical Itrials Iand Iadvance Ito Iphase II
Istudies.
2. Phase II IStudies
A Iphase II Istudy Iuses Ihuman Ivolunteers Ito Itest Ithe Idrugs. IThese Istudies Iare Imore Itightly
Icontrolled Ithan Ipreclinical Itrials Iand Iare Iperformed Iby Ispecially Itrained Iclinical Iinvestigators. IThe
Ivolunteers Iare Ifully Iinformed Iof Ipossible Irisks Iand Imay Ibe Ipaid Ifor Itheir Iparticipation. IUsually,
,the Ivolunteers Iare Ihealthy, Iyoung Imen Iand Ioften Iwomen. IWomen Iof Ichildbearing Ipotential Iare
Isometimes Inot Igood Icandidates Ifor Iphase II Istudies Ibecause Ithe Ichemicals Imay Iexert Iunknown
Iand Iharmful Ieffects Ion Ia Iwoman’s Iova, Iand Itoo Imuch Irisk Iis Iinvolved Iin Itaking Ia Idrug Ithat Imight
Idestroy Ior Ialter Ithe Iova. IWomen Ido Inot Imake Inew Iova Iafter Ibirth. IMen Iproduce Isperm Idaily, Iso
Ithere Iis Iless Ipotential Ifor Icomplete Idestruction Ior Ialteration Iof Ithe Isperm. IVolunteers Iwho Ielect Ito
Iparticipate Iin Iphase II Istudies Ihave Ito Ibe Iinformed Iof Ithe Ipotential Irisks Iand Imust Isign Ia Iconsent
Iform Ioutlining Ithe Ipossible Ieffects.
Some Ichemicals Iare Itherapeutic Iin Iother Ianimals Ibut Ihave Ino Ieffects Iin Ihumans. IInvestigators
in Iphase II Istudies Iscrutinize Ithe Idrugs Ibeing Itested Ifor Ieffects Iin Ihumans. IThey Ialso Ilook Ifor
I
Iadverse Ieffects Iand Itoxicity. IAt Ithe Iend Iof Iphase II Istudies, Imany Ichemicals Iare Idropped Ifrom Ithe
Iprocess Ifor Ithe Ifollowing Ireasons:
• They Icause Iunacceptable Iadverse Ieffects.
• They Iare Ihighly Iteratogenic.
• They Iare Itoo Itoxic.
• They Ilack Ievidence Iof Ipotential Itherapeutic Ieffect Iin Ihumans.
Some Ichemicals Imove Ito Ithe Inext Istage Iof Itesting Idespite Iundesirable Ieffects. IFor Iexample, Ithe
Iantihypertensive Idrug Iminoxidil Iwas Ifound Ito Ieffectively Itreat Imalignant Ihypertension, Ibut Iit
Icaused Iunusual Ihair Igrowth Ion Ithe Ipalms Iand Iother Ibody Iareas. IHowever, Ibecause Iit Iwas Iso Imuch
Imore Ieffective Ifor Itreating Imalignant Ihypertension Iat Ithe Itime Iof Iits Idevelopment Ithan Iany Iother
Iantihypertensive Idrug Iand Ibecause Ithe Iundesired Ieffects Iwere Inot Idangerous, Iit Iproceeded Ito
Iphase III Istudies. I(Now, Iits Ihair-growing Ieffect Ihas Ibeen Ichanneled Ifor Itherapeutic Iuse Iinto
Ivarious Itopical Ihair-growth Ipreparations Isuch Ias IRogaine.)
3. Phase III IStudies
A Iphase III Istudy Iallows Iclinical Iinvestigators Ito Itry Iout Ithe Idrug Iin Ipatients Iwho Ihave Ithe
Idisease Ithat Ithe Idrug Iis Idesigned Ito Itreat. IPatients Iare Itold Iabout Ithe Ipossible Ibenefits Iof Ithe Idrug
Iand Iare Iinvited Ito Iparticipate Iin Ithe Istudy. IThose Iwho Iconsent Ito Iparticipate Iare Ifully Iinformed
Iabout Ipossible Irisks Iand Iare Imonitored Ivery Iclosely, Ioften Iat Ino Icharge Ito Ithem, Ito Ievaluate Ithe
Idrug’s Ieffects. IUsually, Iphase III Istudies Iare Iperformed Iat Ivarious Isites Iacross Ithe Icountry—in
Ihospitals, Iclinics, Iand Idoctors’ Ioffices—and Iare Imonitored Iby Irepresentatives Iof Ithe
Ipharmaceutical Icompany Istudying Ithe Idrug. IAt Ithe Iend Iof Iphase III Istudies, Ia Idrug Imay Ibe
Iremoved Ifrom Ifurther Iinvestigation Ifor Ithe Ifollowing Ireasons:
• It Iis Iless Ieffective Ithan Ianticipated.
• It Iis Itoo Itoxic Iwhen Iused Iwith Ipatients.
• It Iproduces Iunacceptable Iadverse Ieffects.
• It Ihas Ia Ilow Ibenefit-to-risk Iratio, Imeaning Ithat Ithe Itherapeutic Ibenefit Iit Iprovides Idoes Inot
Io utweigh Ithe Irisk Iof Ipotential Iadverse Ieffects Ithat Iit Icauses.
• It Iis Ino Imore Ieffective Ithan Iother Idrugs Ialready Ion Ithe Imarket, Imaking Ithe Icost Iof
Icontinued Iresearch Iand Iproduction Iless Iattractive Ito Ithe Idrug Icompany.
A Idrug Ithat Icontinues Ito Ishow Ipromise Ias Ia Itherapeutic Iagent Ireceives Iadditional Iscrutiny IinIphase
IIII Istudies.
,4. Phase IIII IStudies
A Iphase IIII Istudy Iinvolves Iuse Iof Ithe Idrug Iin Ia Ivast Iclinical Imarket. IPrescribers Iare Iinformed Iof
Ia ll Ithe Iknown Ireactions Ito Ithe Idrug Iand Iprecautions Irequired Ifor Iits Isafe Iuse. IPrescribers Iobserve
Ipatients Ivery Iclosely, Imonitoring Ithem Ifor Iany Iadverse Ieffects. IOften, Iprescribers Iask Ipatients Ito
Ikeep Ijournals Iand Irecord Iany Isymptoms Ithey Iexperience. IPrescribers Ithen Ievaluate Ithe Ireported
Ieffects Ito Idetermine Iwhether Ithey Iare Icaused Iby Ithe Idisease Ior Iby Ithe Idrug. IThis Iinformation Iis
Icollected Iby Ithe Idrug Icompany Ithat Iis Ideveloping Ithe Idrug Iand Iis Ishared Iwith Ithe IFDA. IWhen Ia
Idrug Iis Iused Iwidely Iand Iwithin Iuncontrolled Ienvironments, Itotally Iunexpected Iresponses Imay
Ioccur. IA Idrug Ithat Iproduces Iunacceptable Iadverse Ieffects Ior Iunforeseen Ireactions Iis Iusually
Iremoved Ifrom Ifurther Istudy Iby Ithe Idrug Icompany. IIn Isome Icases, Ithe IFDA Imay Ihave Ito Irequest
Ithat Ia Idrug Ibe Iremoved Ifrom Ithe Imarket.
An Iapproved Idrug Iis Igiven Ia Ibrand Iname I(trade Iname) Iby Ithe Ipharmaceutical Icompany Ithat
Ideveloped Iit. IThe Igeneric Iname Iof Ia Idrug Iis Ithe Ioriginal Idesignation Ithat Ithe Idrug Iwas Igiven
Iwhen Ithe Idrug Icompany Iapplied Ifor Ithe Iapproval Iprocess. IChemical Inames Iare Inames Ithat Ireflect
It he Ichemical Istructure Iof Ia Idrug. ISome Idrugs Iare Iknown Iby Iall Ithree Inames. IIt Ican Ibe Iconfusing
Ito Istudy Idrugs Iwhen Iso Imany Idifferent Inames Iare Iused Ifor Ithe Isame Icompound. IIn Ithis Itext, Ithe
Igeneric Iand Ichemical Inames Ialways Iappear Iin Istraight Iprint, Iand Ithe Ibrand Iname Iis Ialways
Icapitalized Iand Iitalicized I(e.g., Iminoxidil I[Rogaine]).
In Iaddition Ito Ithe Idrug Ilag Iissue, Ithere Ialso Iare Iconcerns Iabout Ithe Ihigh Icost Iof Idrug Iapproval. IIn
2013, IForbes IMagazine Idid Ia Istudy Ithat Ifound Ithat Ithe Iestimated Icost Iof Itaking Ia Ichemical Ifrom
I
Idiscovery Ito Imarketing Ias Ia Idrug Iranged Ifrom I$800 Imillion Ito I$5.3 Ibillion. IBecause Iof Ithis Ikind
Iof Ifinancial Iinvestment, Ipharmaceutical Icompanies Iare Iunwilling Ito Irisk Iapproval Iof Ia Idrug Ithat
Imight Icause Iserious Iproblems Iand Iprompt Ilawsuits.
5. Phase IIV IStudies
After Ia Idrug Iis Iapproved Ifor Imarketing, Iit Ienters Ia Iphase Iof Icontinual Ievaluation, Ior Iphase IIV
Istudy. IPrescribers Iand Iall Ihealthcare Iprofessionals Iare Iobligated Ito Ireport Ito Ithe IFDA Iany
Iuntoward Ior Iunexpected Iadverse Ieffects Iassociated Iwith Idrugs Ithey Iare Iusing, Iand Ithe IFDA
Icontinually Ievaluates Ithis Iinformation. ISome Idrugs Icause Iunexpected Ieffects Ithat Iare Inot Iseen
Iuntil Iwide Idistribution Ioccurs. ISometimes, Ithose Ieffects Iare Itherapeutic. IFor Iexample, Ipatients
It aking Ithe Iantiparkinsonism Idrug Iamantadine I(Symmetrel) Iwere Ifound Ito Ihave Ifewer Icases Iof
Iinfluenza Ithan Iother Ipatients, Ileading Ito Ithe Idiscovery Ithat Iamantadine Iis Ian Ieffective Iantiviral
Iagent.
In Iother Iinstances, Ithe Iunexpected Ieffects Iare Idangerous. IIn I1997, Ithe Idiet Idrug
Idexfenfluramine I(Redux) Iwas Iremoved Ifrom Ithe Imarket Ionly Imonths Iafter Iits Irelease Ibecause
Ipatients Itaking Iit Ideveloped Iserious Iheart Iproblems. IIn I2004, Ithe Idrug Icompany IMerck Iwithdrew
Iits Icyclooxygenase-2 I(Cox-2)-specific Inonsteroidal Ianti-inflammatory Idrug Irofecoxib I(Vioxx)
Ifrom Ithe Imarket Iwhen Ipostmarketing Istudies Iseemed Ito Ishow Ia Isignificant Iincrease Iin
Icardiovascular Imortality Iin Ipatients Iwho Iwere Itaking Ithe Idrug. IThese Iproblems Iwere Inot Iseen Iin
Iany Iof Ithe Ipremarketing Istudies Iof Ithe Idrug. IThe Ieffects Iwere Ionly Iseen Iwith Ia Imuch Iwider Iuse Iof
It he Idrug Iafter Iit Ihad Ibeen Imarketed.
Key IPoints
, • The IFDA Icarefully Iregulates Ithe Itesting Iand Iapproval Iof Iall Idrugs Iin Ithis Icountry.
• To Ibe Iapproved Ifor Imarketing, Ia Idrug Imust Ipass Ithrough Ianimal Itesting, Itesting Ion Ihealthy
Ihumans, Iselected Itesting Ion Ipeople Iwith Ithe Idisease Ibeing Itreated, Iand Ithen Ibroad Itesting
on Ipeople Iwith Ithe Idisease Ibeing Itreated.
The IFDA Ihas Iestablished Ifive Icategories Ito Iindicate Ithe Ipotential Ifor Ia Isystemically Iabsorbed
Idrug Ito Icause Ibirth Idefects.
Category IA: IAdequate Istudies Iin Ipregnant Iwomen Ihave Inot Idemonstrated Ia Irisk Ito Ithe Ifetus
Iin Ithe Ifirst Itrimester Iof Ipregnancy, Iand Ithere Iis Ino Ievidence Iof Irisk Iin Ilater Itrimesters.
Category IB: IAnimal Istudies Ihave Inot Idemonstrated Ia Irisk Ito Ithe Ifetus, Ibut Ithere Iare Ino
Iadequate Istudies Iin Ipregnant Iwomen, Ior I animal Istudies Ihave Ishown Ian Iadverse Ieffect, Ibut
Iadequate Istudies Iin Ipregnant Iwomen Ihave Inot Idemonstrated Ia Irisk Ito Ithe Ifetus Iduring Ithe Ifirst
It rimester Iof Ipregnancy, Iand Ithere Iis Ino Ievidence Iof Irisk Iin Ilater Itrimesters.
Category IC: IAnimal Istudies Ihave Ishown Ian Iadverse Ieffect Ion Ithe Ifetus, Ibut Ithere Iare Ino
Iadequate Istudies Iin Ihumans; Ithe Ibenefits Ifrom Ithe Iuse Iof Ithe Idrug Iin Ipregnant Iwomen Imay Ibe
Iacceptable Idespite Iits Ipotential Irisks, Ior Ithere Iare Ino Ianimal Ireproduction Istudies Iand Ino Iadequate
Istudies Iin Ihumans.
Category ID: IThere Iis Ievidence Iof Ihuman Ifetal Irisk, Ibut Ithe Ipotential Ibenefits Ifrom Ithe Iuse Iof
It he Idrug Iin Ipregnant Iwomen Imay Ibe Iacceptable Idespite Iits Ipotential Irisks.
Category IX: IStudies Iin Ianimals Ior Ihumans Idemonstrate Ifetal Iabnormalities Ior Iadverse
Ireactions; Ireports Iindicate Ievidence Iof Ifetal Irisk. IThe Irisk Iof Iuse Iin Ia Ipregnant Iwoman Iclearly
Io utweighs Iany Ipossible Ibenefit.
Regardless Iof Ithe Idesignated Ipregnancy Icategory Ior Ipresumed Isafety, Ino Idrug Ishould Ibe
administered Iduring Ipregnancy Iunless Iit Iis Iclearly Ineeded.
I
The IControlled ISubstances IAct Iof I1970 Iestablished Icategories Ifor Iranking Iof Ithe Iabuse Ipotential
Iof Ivarious Idrugs. IThis Isame Iact Igave Icontrol Iover Ithe Icoding Iof Idrugs Iand Ithe Ienforcement Iof
Ithese Icodes Ito Ithe IFDA Iand Ithe IDrug IEnforcement IAgency I(DEA), Ia Ipart Iof Ithe IU.S. IDepartment
Io f IJustice. IThe IFDA Istudies Ithe Idrugs Iand Idetermines Itheir Iabuse Ipotential; Ithe IDEA Ienforces
Itheir Icontrol. IDrugs Iwith Iabuse Ipotential Iare Icalled Icontrolled Isubstances. IBox I1.2 Icontains
Idescriptions Iof Ieach Icategory Ior Ischedule.
Drug IEnforcement IAgency ISchedules Iof IControlled ISubstances
The IControlled ISubstances IAct Iof I1970 Iregulates Ithe Imanufacturing, Idistribution, Iand Idispensing
Io f Idrugs Ithat Iare Iknown Ito Ihave Iabuse Ipotential. IThe IDEA Iis Iresponsible Ifor Ithe Ienforcement Iof
Ithese Iregulations. IThe Icontrolled Idrugs Iare Idivided Iinto Ifive IDEA Ischedules Ibased Ion Itheir
Ipotential Ifor Iabuse Iand Iphysical Iand Ipsychological Idependence:
Schedule II I(C-I): IHigh Iabuse Ipotential Iand Ino Iaccepted Imedical Iuse I(heroin, Imarijuana, ILSD)
Schedule III I(C-II): IHigh Iabuse Ipotential Iwith Isevere Idependence Iliability I(narcotics,
Ia mphetamines, Iand Ibarbiturates)
