Yale University Institutional Review Boards

Transcription

1 Yale University Institutinal Review Bards IRB Plicy 630 Requirements fr the Applicatin f Gd Clinical Practice (GCP) t the Cnduct f Clinical Trials Respnsible Office Office f Research Administratin Effective Date May 21, 2013 Respnsible Official Institutinal Review Bard Executive Chair Last Revisin Nvember 4, 2014 Plicy Sectins Institutinal Review Bard (IRB) Respnsibilities Infrmed Cnsent Requirements Vulnerable Ppulatins Investigatr Qualificatins Investigatr Respnsibilities... 4 Scpe This plicy describes the requirements, in additin t the Department f Health and Human Services (DHHS) Office f Human Research Prtectins (OHRP) and Fd and Drug Administratin (FDA) regulatins and Yale University Human Research Prtectin Prgram (HRPP) plices and prcedures, fr clinical trials invlving human subjects t be cmpliant with Guidance fr Industry E6 Gd Clinical Practice: Cnslidated Guidance (ICH-GCP Guidance (E6)). Nte: In the United States, the FDA has adpted GCP as guidance and nt a regulatry requirement. Plicy Statement The Yale University Institutinal Review Bards (IRBs) cmply with ICH GCP guidance (E6) nly t the extent that it is cmpatible with FDA and DHHS regulatins. Hwever, fr industry-spnsred studies with cntract requirements fr institutinal adherence t ICH GCP guidance (E6), the Yale University IRBs will cmply with all f the GCP statements utlined in the ICH-GCP (E6) guidance, prvided that: a) The Principal Investigatr (PI) indicates in the Human Investigatin Cmmittee (HIC) applicatin(s) that the spnsr requires the IRB review prcess t cmply with ICH standards, and b) The Grants and Cntracts Administratin (GCA) Office cnfirms it is a cntractual requirement Nte: Studies invlving nly behaviral interventins are nt cvered by this plicy. Reasn fr the Plicy Gd Clinical Practice (GCP) guidance is an internatinal ethical and scientific quality standard fr designing, cnducting, recrding, and reprting clinical trials in human subjects that was develped by the Internatinal Cnference n Harmnisatin f Technical Requirements fr the Registratin f Pharmaceuticals fr Human Use (ICH). The GCP guidance develped by ICH is based n FDA regulatins fr the prtectin f human subjects and defines the rles and respnsibilities f Institutinal Review Bards (IRBs), investigatrs, mnitrs, and spnsrs. General principles f ICH & GCP include, but are nt limited t: 1. Clinical trials shuld be cnducted in accrdance with the ethical principles that have their rigin in the Declaratin f Helsinki, and that are cnsistent with GCP and the applicable regulatry requirement(s) (ICH-GCP 2.1) 2. The available nnclinical and clinical infrmatin n an investigatinal prduct shuld be adequate t supprt the prpsed clinical trial. (ICH-GCP 2.4) 3. Clinical trials shuld be scientifically sund, and described in a clear, detailed prtcl. (ICH-GCP 2.5) 4. Investigatinal prducts shuld be manufactured, handled, and stred in accrdance with applicable gd manufacturing practice (GMP). They shuld be used in accrdance with the apprved prtcl. (ICH-GCP 2.12)

2 Definitins IRB Plicy 630 ICH/GCP fr Clinical Trials Clinical Trial/Study Any investigatin in human subjects intended t: discver r verify clinical, pharmaclgical, and/r ther pharmacdynamic effects f an investigatinal prduct; identify any adverse reactins t an investigatinal prduct; and/r study absrptin, distributin, metablism, and excretin f an investigatinal prduct t determine its safety and/r efficacy. The terms clinical trial and clinical study are synnymus. (ICH-GCP 1.12) Gd Clinical Practice (GCP): Als referred t as ICH E6. A standard established by the Internatinal Cnference n Harmnizatin fr the design, cnduct, perfrmance, mnitring, auditing, recrding, analyses, and reprting f clinical trials that prvides assurance that the data and reprted results are credible and accurate, and that the rights, integrity, and cnfidentiality f clinical trial subjects are prtected. (ICH-GCP 1.24) Internatinal Cnference n Harmnisatin f Technical Requirements fr the Registratin f Pharmaceuticals fr Human Use (ICH). Vluntary, internatinal initiative t increase crdinatin f the requirements fr develping and marketing new drugs. The ICH includes representatives frm the pharmaceutical industry and regulatry authrities frm the United States, Japan and the Eurpean Unin. Investigatinal Prduct A pharmaceutical frm f an active ingredient r placeb being tested r used as a reference in a clinical trial, including a prduct with marketing authrizatin when used r assembled (frmulated r packaged) in a way different frm the apprved frm, r when used fr an unapprved indicatin, r when used t gain further infrmatin abut an apprved use. (ICH-GCP 1.33) Investigatr A persn respnsible fr the cnduct f the clinical trial at a trial site. If a trial is cnducted by a team f individuals at a trial site, the investigatr is the respnsible leader f the team and may be called the principal investigatr. (ICH-GCP 1.34) Legally Acceptable Representative An individual r judicial r ther bdy authrized under applicable law t cnsent, n behalf f a prspective subject, t the subject s participatin in the clinical trial. (ICH-GCP 1.37) Nte: Legally Acceptable Representative is nly used in this cntext fr clinical trials that fllw ICH-GCP (E6) as listed in the plicy statement. Spnsr-Investigatr An individual wh bth initiates and cnducts, alne r with thers, a clinical trial, and under whse immediate directin the investigatinal prduct is administered t, dispensed t, r used by a subject. The term des nt include any persn ther than the individual (e.g., it des nt include a crpratin r an agency). The bligatins f a spnsr-investigatr include bth thse f a spnsr and thse f an investigatr. (ICH-GCP 1.54) Plicy Sectins Institutinal Review Bard (IRB) Respnsibilities Yale University vluntarily apply the ICH-GCP (E6) Guidelines t certain types f human subjects research cnducted under its Human Research Prtectin Prgram. In general, Yale University apply ICH-GCP guidelines nly t the extent that they are cmpatible with FDA and DHHS regulatins. When a spnsr requires institutinal ICH-GCP cmpliance, the IRB will cnduct a review in accrd with ICH-GCP requirements. T be apprved, clinical trials must satisfy the requirements described in the Human Research Prtectin Prgram (HRPP) plicies and prcedures (see IRB Plicy 100 IRB Review f Research Prtcls Invlving Human Participants]. Trial prtcl(s)/amendment(s), written infrmed cnsent frm(s) and cnsent frm updates that the investigatr prpses fr the use in the trial, subject recruitment prcedures (e.g., advertisements), written infrmatin t be prvided t the subjects, Investigatr s Brchure (IB), available safety infrmatin, infrmatin abut payments and cmpensatin available t subjects, the investigatr s current curriculum vitae and/r ther dcumentatin evidencing qualificatins, and any ther dcuments that the IRB may require t fulfill its respnsibilities. (ICH-GCP 3.1.2) 5/21/13 Page 2 f 6

3 IRB Plicy 630 ICH/GCP fr Clinical Trials Yale University HRPP/IRB Practice Differences: The investigatr s current curriculum vitae (CV) is nt requested at the time f submissin f the prtcl t the IRB. The qualificatins f the investigatr are cnfirmed and apprved by the investigatr s Department Chair prir t submissin t the Human Investigatin Cmmittee (HIC). The IRB verifies that the investigatr has cmpleted all requisite training and is in cmpliance with cnflict f interest training and financial disclsure plicies. In additin, the investigatr is required t reprt n the IRB applicatin whether r nt their hspital privileges allw them t perfrm the specific prcedures utlined in the prtcl and directs them t the Hspital Department f Physician Services, shuld credentialing be required Infrmed Cnsent Requirements In additin t the required elements f cnsent disclsure described by HRPP Plicy 200: Infrmed Cnsent fr Research Invlving Human Participants and the ICH-GCP 4.8 Infrmed Cnsent f Trial Subjects infrmed cnsent disclsures will include the fllwing: That the mnitr(s), the auditr(s), the IRB, and the regulatry authrity(ies) will be granted direct access t the subject s riginal medical recrds fr verificatin f clinical trial prcedures and/r data, withut vilating the cnfidentiality f the subject, t the extent permitted by the applicable laws and regulatins and that, by signing a written infrmed cnsent frm, the subject r the subject s legally acceptable representative is authrizing such access. (ICH-GCP (n)) Prir t the beginning f the trial, the investigatr shuld have the IRB written apprval f the written infrmed cnsent frm and any ther written infrmatin t be prvided t the subjects. (ICH-GCP 4.8.1) Dcumentatin f the infrmed cnsent f clinical trial subjects prcess include: Prir t a subject s participatin in the trial, the written infrmed cnsent frm shuld be signed and persnally dated by the subject r by the subjects legally acceptable representative (LAR), and by the persn wh cnducted the infrmed cnsent discussin. (ICH-GCP 4.8.8) If a subject is unable t read r if a legally acceptable representative is unable t read, an impartial witness shuld be present during the entire infrmed cnsent discussin. After the written infrmed cnsent and any ther written infrmatin t be prvided t subjects, is read and explained t the subject r subject s legally acceptable representative, and after the subject r the subject s legally acceptable representative has rally cnsented t the subject s participatin in the trial and, if capable f ding s, has signed and persnally dated the infrmed cnsent frm, the witness shuld sign and persnally date the cnsent frm. By signing the cnsent frm, the witness attests that the infrmatin in the cnsent frm and any ther written infrmatin was accurately explained t, and apparently understd by, the subject r subject s legally acceptable representative, and that infrmed cnsent was freely given by the subject r subject s legally acceptable representative. (ICH-GCP 4.8.9) Prir t participatin in the trial, the subject r the subject s legally acceptable representative shuld receive a cpy f the signed and dated written infrmed cnsent frm and any ther written infrmatin prvided t the subjects. (ICH-GCP ) Vulnerable Ppulatins Except as described belw (ICH-GCP ), a nntherapeutic trial (i.e., a trial in which there is n anticipated direct clinical benefit t the subject shuld be cnducted in subjects wh persnally give cnsent and wh sign and date the written infrmed cnsent frm (ICH-GCP ) Nn-therapeutic clinical trials may be cnducted in subjects with cnsent f a legally acceptable representative prvided the fllwing cnditins are fulfilled: The bjectives f the clinical trial cannt be met by means f a trial in subjects wh can give cnsent persnally The freseeable risks t the subjects are lw The negative impact n the subject s well being is minimized and lw The clinical trial is nt prhibited by law 5/21/13 Page 3 f 6

4 IRB Plicy 630 ICH/GCP fr Clinical Trials The apprval/favrable pinin f the IRBs is expressly sught n the inclusin f such subjects and the written apprval/favrable pinin cvers this aspect Such trials, unless an exceptin is justified, shuld be cnducted in patients having a disease r cnditin fr which the investigatinal prduct is intended. Subjects in these trials shuld be particularly clsely mnitred and shuld be withdrawn if they appear t be unduly distressed. (ICH-GCP ) Investigatr(s) Qualificatins 1. The Investigatr(s) shuld be qualified by educatin, training, and experience t assume respnsibility fr the prper cnduct f the trial, shuld meet all the qualificatins specified by the applicable regulatry requirement(s), and shuld prvide evidence f such qualificatins thrugh up-t-date curriculum vitae and/r ther relevant dcumentatin requested by the spnsr, the IRB, and/r the regulatry authrity (ies). (ICH-GCP 4.1.1) Yale University Practice Differences: See abve under The investigatr shuld be thrughly familiar with the apprpriate use f the investigatinal prduct(s), as described in the prtcl, in the current Investigatr s Brchure, in the prduct infrmatin, and in ther infrmatin surces prvided by the spnsr. (ICH-GCP 4.1.2) 3. A qualified physician (r dentist, when apprpriate), wh is an investigatr r a sub-investigatr fr the trial, shuld be respnsible fr all trial-related medical (r dental) decisins. (ICH-GCP 4.3.1) 4. The investigatr shuld be aware f, and shuld cmply with, GCP and the applicable regulatry requirements. (ICH-GCP 4.1.3) 5. The investigatr/institutin shuld permit mnitring and auditing by the spnsr, and inspectin by the apprpriate regulatry authrity(ies). (ICH-GCP 4.1.4) 6. The investigatr shuld maintain a list f apprpriately qualified persns t whm the investigatr has delegated significant trial-related duties. (ICH-GCP 4.1.5) Investigatr Respnsibilities In rder t satisfy the ICH-GCP (E6) requirements, Investigatrs wh cnduct research invlving human subjects must satisfy the fllwing: 1. During and fllwing a subject s participatin in a trial, the investigatr/institutin shuld ensure that adequate medical care is prvided t a subject fr any adverse events, including clinically significant labratry values, related t the clinical trial (ICH-GCP 4.3.2) 2. The investigatr infrms a subject when medical care is needed fr ther illnesses f which the investigatr becmes aware (ICH-GCP 4.3.2) 3. The investigatr shuld fllw the trial s randmizatin prcedures, if any, and shuld ensure that the cde is brken nly in accrdance with the prtcl. If the trial is blinded, the investigatr shuld prmptly dcument and explain t the spnsr any premature unblinding (e.g. accidental unblinding, unblinding due t a serius adverse event) f the investigatinal prduct(s) (ICH-GCP 4.7) 4. It is recmmended that the investigatr infrms the subject s primary physician abut the subject s participatin in the trial if the subject has a primary physician an if the subject agrees t the primary physician being infrmed (ICH-GCP 4.3.3) 5. Althugh a subject is nt bliged t give his r her reasn(s) fr withdrawing prematurely frm a trial, the investigatr shuld make a reasnable effrt t ascertain the reasn(s), while fully respecting the subject s rights (ICH-GCP 4.3.4) 6. Where allwed, the investigatr may assign sme r all duties fr investigatinal prduct(s) accuntability at the trial site(s) t an apprpriate pharmacist r ther apprpriate individual wh is under the supervisin f the investigatr and/r institutin. (ICH-GCP 4.6.2) 7. The investigatr, pharmacist, r ther apprpriate individual, wh is designated by the investigatr and/r institutin, shuld maintain recrds f the prduct s delivery t the trial site, the inventry f the site, the use by each subject, and the return t the spnsr r alternative 5/21/13 Page 4 f 6

5 IRB Plicy 630 ICH/GCP fr Clinical Trials dispsitin f unused prduct(s). These recrds will include dates, quantities, batch/serial numbers, expiratin dates (if applicable), and the unique cde numbers assigned t the investigatinal prducts and trial subjects. Investigatrs shuld maintain recrds that dcument adequately that the subjects were prvided the dses specified by the prtcl and recncile all investigatinal prduct(s) received frm the spnsr. (ICH-GCP 4.6.3) 8. The investigatr permits mnitring and auditing by the spnsr, and inspectin by the apprpriate regulatry authrity. (ICH-GCP 4.1.4) 9. The investigatr ensures the accuracy, cmpleteness, legibility, and timeliness f the data reprts t the spnsr. (ICH-GCP 4.9.1) 10. Adverse events and/r labratry abnrmalities identified in the prtcl as critical t safety evaluatins shuld be reprted t the spnsr accrding t the reprting requirements and within the time perids specified by the spnsr in the prtcl. (ICH-GCP ) 11. The investigatr reprts all serius adverse events (SAEs) t the spnsr except thse SAEs that the prtcl r ther dcument (e.g., investigatr s brchure) identifies as nt needing immediate reprting. The investigatr fllws regulatry requirements related t the reprting f unexpected serius adverse drug reactins t the regulatry authrity and the IRB. (ICH- GCP ) 12. The investigatr shuld prmptly prvide written reprts t the spnsr, the IRB, and where required by the applicable regulatry requirements, the institutin n any changes significantly affecting the cnduct f the trial and/r increasing the risk t subjects. (ICH-GCP ) 13. If the investigatr terminates r suspends a trial withut prir agreement f the spnsr, the investigatr shuld infrm the institutin, where required by the applicable regulatry requirements, and the investigatr/institutin shuld prmptly infrm the spnsr and the IRB, and shuld prvide the spnsr and the IRB a detailed written explanatin f the terminatin r suspensin (ICH-GCP ) 14. If the IRB terminates r suspends its apprval/favrable pinin f a trial, the investigatr shuld infrm the institutin, where required by the applicable regulatry requirements, and the investigatr/institutin shuld prmptly ntify the spnsr and prvide the spnsr with a detailed written explanatin f the terminatin r suspensin. (ICH-GCP ) 15. Upn cmpletin f the trial, the investigatr shuld, where required by the applicable regulatry requirements, infrm the institutin, and the investigatr/institutin shuld prvide the spnsr with all required reprts, the IRB with a summary f the trial s utcme, and the regulatry authrity(ies) with any reprt(s) they require f the investigatr/institutin. (ICH-GCP 4.13) 16. Fr reprted deaths, the investigatr shuld supply the spnsr and the IRB with any additinal requested infrmatin (e.g. autpsy reprts and terminal medical reprts). (ICH-GCP ) Related Infrmatin Internatinal Cnference n Harmnisatin f Technical Requirements fr Registratin f Pharmaceuticals fr Human Use, Guidance fr Gd Clinical Practice E6 AAHRPP Tip Sheet 11: Fllwing the Guidelines f the Internatinal Cnference n Harmnizatin Gd Clinical Practice (E6) ( ) ICH Guidance fr Industry: E6 Gd Clinical Practice: Cnslidated Guidance (04/96) 100 PR 4, Department f Defense Supprted Research 200 PR 1: Infrmed Cnsent fr Research Participatin: Cmpetent Adult Participants 200 PR 2: Exceptin Frm Infrmed Cnsent (EFIC) Research 200 GD 2: Guidance n the Inclusin f Nn-English Speaking Participants in Human Research 200 FR 1: Cnsent Template Bimedical Research 200 FR 3: Sample Shrt Frm Cnsent 5/21/13 Page 5 f 6

6 IRB Plicy 630 ICH/GCP fr Clinical Trials 200 CH 1: Human Investigatin Cmmittee Infrmed Cnsent Checklist 310 PR.1 Infrmed Cnsent in Research Invlving Children 310 FR.1: Assent Template Plicy 340: Participatin f Individuals with Impaired Cnsent Capacity 340 PR 1: Assessment f Capacity t Cnsent Plicy 600 Use f Investigatinal New Drugs and Devices In Human Research 600 PR 1: Emergency Use f an Investigatinal New Drug (IND) r Device (IDE) 600 FR 2: Infrmed Cnsent Dcument fr Emergency Use Investigatinal Drug r Device. Cntacts Gd Clinical Practices Subject Cntact Phne/ Human Investigatin Cmmittee hrpp@yale.edu Rles and Respnsibilities Human Research Prtectin Prgram (HRPP) The Human Research Prtectin Prgram is respnsible fr versight f human research prtectin thrugh nging educatin, mnitring, and evaluatin f all parties invlved in the cnduct f human research. Human Investigatin Cmmittee (HIC) The HIC I, HIC II, HIC III and HIC IV serve as the fur Institutinal Review Bards r IRBs fr bimedical human research cnducted at Yale University. Human Subjects Cmmittee (HSC) The HSC serves as the Institutinal Review Bard fr scial, behaviral and educatinal human research at Yale University. Revisin Histry 11/4/ /30/2015 5/21/13 Page 6 f 6