ClinicalTrials.gov Registration and Reporting Final Rule (FDA Amendments Act Section 801) FAQs

Transcription

1 ClinicalTrials.gv Registratin and Reprting Final Rule (FDA Amendments Act Sectin 801) FAQs 15 August

2 Final Rule FAQs UQ: When is the effective date and cmpliance date f the Final Rule? UEffective Date:U 18 January 2017 UCmpliance Date:U 18 April 2017 UQ: Which Clinical Trials are Subject t the Requirements ( Applicable Clinical Trials )? A: Registratin and results infrmatin reprting is required fr any trial fr which the fllwing is true: The study is a pediatric pstmarket surveillance f a device prduct UOR Study type is interventinal Primary purpse is NOT device feasibility Studies an FDA-regulated device prduct AND One r mre f the fllwing: At least 1 US facility lcatin Prduct manufactured in and exprted frm the US Cnducted under an FDA IDE OR (fr Drug/Bilgic) Study type is interventinal Study phase is NOT Phase 1 Studies an FDA-regulated drug prduct (including bilgics) AND One r mre f the fllwing: At least 1 US facility lcatin Prduct manufactured in and exprted frm the US Cnducted under an FDA IND UQ: Des my trial meet the NIH definitin f a clinical trial? 1) Des the study invlve human participants? 2) Are the participants prspectively assigned t an interventin (which may include placeb r ther cntrl)? 3) Is the study designed t evaluate the effect f the interventin n the participants? 2

3 4) Is the effect that will be evaluated a health-related bimedical r behaviral utcme? If the answer t all fur questins is UyesU, then yur prpsed research Umeets the NIH definitin f a clinical trialu. This definitin encmpasses a wide range f trial types: mechanistic, explratry/develpmental, pilt/feasibility, behaviral, and mre. UQ: Are any types f trials/studies exempt frm the requirements? The fllwing types f studies are generally excluded frm the registratin and results submissin requirements f FDAAA 801 (nn-exhaustive list): Phase 1 drug trials, including studies in which investigatinal drugs are used as research tls t explre bilgical phenmena r disease prcesses Small clinical trials t determine feasibility f a device r a clinical trial t test prttype devices, where the primary utcme measure(s) relates t feasibility and nt t health utcmes Trials that d nt include drugs, bilgics, r devices (e.g., behaviral interventins) Nn-interventinal (bservatinal) clinical research (e.g., chrt r case-cntrl studies) Trials that were nging as f 27 September 2007 and reached the Primary Cmpletin Date (see definitin) befre 26 December 2007 UNOTE:U Trials may be subject t the Vluntary Submissin prvisin f FDAAA 801. UAccess the fllwing hyperlinks fr further guidance and specificity: 33TUhttps://grants.nih.gv/clinicaltrials_fdaaa/ACTs_under_FDAAA.htm (FDAAA Decisin Tree Tl - flwchart) 33TUhttps://grants.nih.gv/plicy/clinical-trials/definitin.htm UIt shuld be nted that ALLU NIH-funded clinical trials, whether funded in whle r in part, regardless f study phase, type f interventin, r whether subject t regulatin must be registered and summary results infrmatin reprted t ClinicalTrials.gv. UQ: What Registratin and Reprting Infrmatin is Required? Fr URegistratinU f Applicable Clinical Trials initiated Ubefre 18 January 2017U: 1. Descriptive infrmatin abut the trial: Brief Title Brief Summary Primary Purpse Study Design Study Phase (fr an applicable drug clinical trial) Study Type Primary Disease r Cnditin Being Studied, r the Fcus f the Study 3

4 Interventin Name Interventin Type Study Start Date Expected Cmpletin Date Target Number f Subjects Outcmes, Including Primary and Secndary Outcme Measures 2. Recruitment infrmatin: Eligibility Criteria Gender Age Limits Whether the trial accepts healthy vlunteers Overall Recruitment Status Individual Site Status Availability f Expanded Access fr thse wh d nt qualify fr enrllment in the trial and hw t btain infrmatin abut such access 3. Lcatin/Cntact infrmatin: Name f the Spnsr Respnsible Party (by Official Title) Facility Name and Cntact Infrmatin (including City, State and Zip Cde fr each clinical trial lcatin, r a tll-free number thrugh which lcatin infrmatin can be accessed) 4. Administrative Data: Unique Prtcl Identificatin Number Other Prtcl Identificatin Numbers, if any U.S. FDA IND r IDE Prtcl Number Recrd Verificatin Date Fr URegistratinU f Applicable Clinical Trials initiated Un r after 18 January 2017UP1P: 1. Descriptive infrmatin abut the trial: Brief Title Official Title Brief Summary Primary Purpse Study Design Study Phase (fr an applicable drug clinical trial) Study Type Pediatric Pstmarket Surveillance f a Device Prduct, fr an applicable device clinical trial that is a Pediatric Pstmarket Surveillance f a Device Prduct Primary Disease r Cnditin Being Studied in the Trial, r the Fcus f the Study Interventin Name(s), fr each interventin studied 4

5 Other Interventin Name(s), fr each interventin studied Interventin Descriptin, fr each interventin studied Interventin Type, fr each interventin studied Studies an FDA-regulated Device Prduct/Drug Prduct Device Prduct Nt Apprved/Cleared by the FDA, if any studied interventin is a device prduct Pst prir t FDA Apprval/Clearance, fr an applicable device clinical trial that studies at least ne device prduct nt previusly apprved/cleared by the FDA Prduct Manufactured in and Exprted frm the U.S., if the entry fr FDA IND r IDE Number indicates that there is n IND/IDE fr the clinical trial, and the entry(-ies) fr Facility Infrmatin include n facility lcatins in the U.S. r its territries Study Start Date Primary Cmpletin Date Study Cmpletin date Enrllment Primary Outcme Measure Infrmatin, fr each primary utcme measure Secndary Outcme Measure Infrmatin, fr each secndary utcme measure 2. Recruitment infrmatin: Eligibility criteria Sex/Gender Age Limits If the trial accepts healthy vlunteers Overall Recruitment Status If ended prematurely, Why Study Stpped Individual Site Status Availability f Expanded Access. If available fr an IND, an expanded access recrd must be submitted in accrdance with 21 CFR 11.28(c), unless previusly submitted 3. Lcatin/Cntact infrmatin: Name f the Spnsr Respnsible Party (by Official Title) Facility Infrmatin 4. Administrative Data: Unique Prtcl Identificatin Number Secndary ID U.S. FDA IND r IDE Number Human Subjects Prtectin Review Bard Status Recrd Verificatin Date Respnsible Party Cntact Infrmatin P1 PSubsets f the abve elements are required fr Pediatric Pstmarket Surveillance f a Device Prduct that is UntU a clinical trial and fr Expanded Access Recrds. 5

6 Fr UReprting UResults f Applicable Clinical Trials where the Primary Cmpletin Date is Ubefre 18 January 2017U (if cllected)p1p: Unless a waiver f the requirement t submit clinical trial results infrmatin is granted in accrdance with 42 CRF 11.54, if the Applicable Clinical Trial studies a drug, bilgical, r device prduct that is apprved, licensed r cleared as f the Primary Cmpletin Date, then the respnsible party is required t submit results infrmatin, as fllws: 1. Demgraphic and baseline characteristics f patient sample A table f the demgraphic and baseline data cllected verall and fr each arm f the clinical trial t describe the patients wh participated in the clinical trial, including the number f patients wh drpped ut f the clinical trial and the number f patients excluded frm the analysis, if any. 2. Primary and secndary utcmes The primary and secndary utcme measures and a table f values fr each f the primary and secndary utcme measures fr each arm f the clinical trial, including the results f scientifically apprpriate tests f the statistical significance f such utcme measures. 3. Pint f cntact A pint f cntact fr scientific infrmatin abut the clinical trial results. 4. Certain agreements Whether there exists an agreement (ther than an agreement slely t cmply with applicable prvisins f law prtecting the privacy f participants) between the spnsr r its agent and the principal investigatr (unless the spnsr is an emplyer f the principal investigatr) that restricts in any manner the ability f the principal investigatr, after the cmpletin date f the trial, t discuss the results f the trial at a scientific meeting r any ther public r private frum, r t publish in a scientific r academic jurnal infrmatin cncerning the results f the trial. 5. Serius adverse events A table f anticipated and unanticipated serius adverse events gruped by rgan system, with number and frequency f such event in each arm f the clinical trial. 6. Frequent adverse events A table f anticipated and unanticipated adverse events that are nt included in the table described abve that exceed a frequency f 5 percent within any arm f the clinical trial, gruped by rgan system, with number and frequency f such event in each arm f the clinical trial. If the Applicable Clinical Trial studies a drug, bilgical, r device prduct that is Unt Uapprved, licensed, r cleared as f the Primary Cmpletin Date, then the respnsible party is UntU required t submit results infrmatin. Fr UReprting UResults f Applicable Clinical Trials where the Primary Cmpletin Date is Un r after 18 January 2017U (if cllected)p1p: 6

7 Unless a waiver f the requirement t submit clinical trial results infrmatin is granted in accrdance with 42 CRF 11.54, if the Applicable Clinical Trial studies a drug, bilgical, r device prduct, then the respnsible party is required t submit results infrmatin, as fllws: 1. Participant Flw: Infrmatin dcumenting the prgress f human subjects thrugh a clinical trial, by arm, including the number wh started and cmpleted the trial. This includes the fllwing elements: Participant Flw Arm Infrmatin Pre-assignment Infrmatin Participant Data 2. Demgraphic and Baseline Characteristics: Infrmatin dcumenting demgraphic and baseline measures and data cllected by arm r cmparisn grup and fr the entire ppulatin f human subjects wh participated in the clinical trial. This includes the fllwing elements: Baseline Characteristics Arm/Grup Infrmatin Baseline Analysis Ppulatin Infrmatin Overall Number f Baseline Participants Overall Number f Units Analyzed Analysis Ppulatin Descriptin Baseline Measure Infrmatin Name and Descriptin f the Measure Measure Type and Measure f Dispersin Unit f Measure Baseline Measure Data Number f Baseline Participants (and Units) by Arm r Cmparisn Grup and Overall, if different frm the Overall Number f Baseline Participants r Overall Number f Units Analyzed Infrmatin in Sectin 2 abve generally encmpasses Age, Sex and Gender, Race r Ethnicity, as well as ther measures that were assessed at baseline and are used in analysis f primary utcme measures. 3. Outcmes and Statistical Analyses: Infrmatin fr each primary and secndary utcme measure by arm r cmparisn grup, including result(s) f scientifically apprpriate statistical analyses that were perfrmed n the utcme measure data, if any. This includes the fllwing elements: Outcme Measure Arm/Grup Infrmatin Analysis Ppulatin Infrmatin Number f Participants Analyzed Number f Units Analyzed Analysis Ppulatin Descriptin Outcme Measure Infrmatin Name f the Specific Outcme Measure 7

8 Descriptin f the Metric Used t Characterize the Specific Outcme Measure Time pint(s) at which the Measurement was Assessed fr the Specific Metric Outcme Measure Type Measure Type and Measure f Dispersin r Precisin Unit f Measure Outcme Measure Data Statistical Analyses 4. Adverse Event Infrmatin: Infrmatin t describe the methds fr cllecting Adverse Events during an Applicable Clinical Trial: Time Frame The specific perid f time ver which AE infrmatin was cllected and fr which infrmatin is submitted AE reprting descriptin (if the AE infrmatin cllected in the clinical trial is cllected based n a different definitin f AE and/r SAE frm that used in Final Rule) Cllectin apprach used t cllect AE infrmatin, whether systematic r nnsystematic Infrmatin fr cmpleting three tables summarizing anticipated and unanticipated AEs cllected during an Applicable Clinical Trial: Table f all SAEs gruped by rgan system, with the number and frequency f each event by arm r cmparisn grup Table f all AEs, ther than SAEs, that exceed a frequency f 5% within any arm f the clinical trial, gruped by rgan system, with the number and frequency f each event by arm r cmparisn grup Table f all-cause mrtality, with the number and frequency f deaths due t any cause by arm r cmparisn grup (= all cause deaths) Infrmatin fr each table specified abve must include the fllwing elements, unless therwise specified: Adverse Event Arm/Grup Infrmatin Ttal Number Affected. The verall number f human subjects affected, by arm r cmparisn grup, by: SAEs AEs ther than SAEs that exceed a 5% frequency within any arm f the clinical trial Deaths due t any cause Ttal Number at Risk. The verall number f human subjects included in the assessment, by arm r cmparisn grup, fr: SAEs AEs ther than SAEs that exceed a 5% frequency within any arm f the clinical trial Deaths due t any cause 8

9 Adverse Event Infrmatin. Fr the tw tables described directly abve, a descriptin f each type f SAE and ther AE that is nt an SAE and exceeds a frequency f 5% within any arm f the clinical trial, cnsisting f the fllwing attributes: Descriptive term fr the AE Organ system assciated with the AE Adverse Event Data. Fr the tw tables described abve, and fr each AE listed IAW the Adverse Event Infrmatin abve: Number f human subjects affected by such AE Number f human subjects at risk fr such AE 5. Prtcl and Statistical Analysis Plan (SAP): A cpy f the apprved prtcl and the SAP (if nt included in the prtcl), including all amendments that have been apprved by a human subjects prtectin review bard befre the time f submissin and that apply t all clinical trial Facility Lcatins T be submitted at time f results infrmatin reprting (ptin t submit earlier) ICFs are ptinal 6. Administrative Infrmatin: Results Pint f Cntact fr scientific infrmatin abut clinical trial results infrmatin: Name r fficial title f the Pint f Cntact Name f the affiliated rganizatin Telephne number and address f the Pint f Cntact 7. Additinal Clinical Trial Results Infrmatin fr Applicable Device Clinical Trials f Unapprved r Uncleared Device Prducts P1 P Subsets f the abve elements are required fr Pediatric Pstmarket Surveillance f a Device Prduct that is UntU a clinical trial. UQ: What are the requirements fr updating clinical trial registratin infrmatin nce a Human Subjects Review Bard apprves a prtcl amendment? Fr applicable clinical trials initiated n r after 18 January 2017, r fr which registratin infrmatin was vluntarily submitted pursuant t 42 CFR 11.60(c), if a prtcl is amended in such a manner that changes are cmmunicated t human subjects in the clinical trial, updates t any relevant clinical trial registratin infrmatin data elements must be submitted Un later than 30 calendar days after the prtcl amendmentu Uis apprved by a human subjects prtectin review bardu. If there is mre than ne human subjects prtectin review bard fr a multi-site trial, the date f the first bard apprval fr the amendment shuld be used. UQ: What ther registratin updates are required t be made t Applicable Clinical Trials in ClinicalTrials.gv? 9

10 18 Respnsible Parties shuld update their recrds in ClinicalTrials.gv Uwithin 30 daysu f a change t any f the fllwing: Recruitment Status and Overall Recruitment Status Primary Cmpletin Date and Cmpletin Date Other changes r updates t the recrd, such as prtcl amendments, must be made at least every 12 mnths. It is recmmended that the Recrd Verificatin Date be updated at least every 6 mnths fr studies that are nt yet cmpleted, even if there were n changes t the recrd. UQ: Is a prtcl and statistical analysis plan (SAP) required t be submitted? The regulatins UrequireU a cpy f the Uprtcl and SAPU (if nt included in the prtcl) t be submitted as part f clinical trial results infrmatin fr thse applicable clinical trials with a Primary Cmpletin Date Un r after U January The submissin f a prtcl and SAP is nt required fr thse applicable clinical trials with a Primary Cmpletin Date befre 18 January UQ: Must applicable clinical trials with n external surces f funding ("unfunded" studies) be registered in ClinicalTrials.gv? Applicable clinical trials with n external surces f funding are UntU excluded frm the requirements described in FDAAA 801. In general, an unfunded study shuld be registered by the Spnsr. When an investigatr is cnsidered the Spnsr (e.g., a Spnsr-Investigatr), the study shuld be registered by the investigatr's affiliated institutin with the Respnsible Party indicated as Spnsr-Investigatr. ClinicalTrials.gv will then display the investigatr as the Spnsr instead f the investigatr's institutin. UQ: Hw shuld results infrmatin be submitted fr applicable clinical trials that are terminated prir t cmpletin, r therwise stpped prematurely, and fr which n data were cllected fr ne r mre Outcme Measures? If n participants were ever enrlled, the Overall Recruitment Status in ClinicalTrials.gv shuld be set t Withdrawn. N results infrmatin will need t be submitted. Fr trials that were terminated after participants were enrlled, any available data shuld be prvided. If n data are available fr any f the Outcme Measures, zer ("0") shuld be specified fr the Number f Participants Analyzed in each Arm/Grup and the data fields shuld be left blank. An explanatin shuld be prvided in the Analysis Ppulatin Descriptin t indicate why n participants were analyzed and, if apprpriate, infrmatin shuld be prvided in the Limitatins and Caveats mdule. Even if data are nt entered fr Outcme Measures, available data fr the enrlled participants shuld be included in the Participant Flw, Baseline Characteristics, and Adverse Events mdules. Investigatr and crdinatr FAQ s 10

11 1. Shuld yu register yur research prject with ClinicalTrials.gv YES, Register yur study at the NIH website, UClinicalTrials.gv U. YES, if yu want t publish the results f yur study If yu wish t publish yur study in a peer-reviewed jurnal, then it is highly likely that the jurnal will expect yur study t have been registered with ClinicalTrials.gv. Thusands f jurnals have adpted the plicy f the Internatinal Cmmittee f Medical Jurnal Editrs (ICMJE) that requires registratin in a publicly available register. YES, because in sme cases, IT S THE LAW A small subset f studies is required by law t be registered with ClinicalTrials.gv. The FDA Amendments Act (FDAAA) f 2007 required that mst prspective studies invlving regulated drugs, bilgical prducts, and medical devices must be registered n ClinicalTrials.gv. The law als requires reprting f basic results and adverse events fr a subset f these studies. In additin, UALLU NIHfunded clinical trials, whether funded in whle r in part by the NIH, regardless f study phase, type f interventin, r whether subject t regulatin, must be registered and summary results infrmatin reprted t ClinicalTrials.gv. 2. When d I have t register my study? ICMJE requires that yu register prir t enrllment f yur first study participant. The law (i.e., UFinal Rule (42 CFR Part 11)U requires that a study be registered within 21 days f enrllment f the first participant. In accrdance with the Final Rule (42 CFR Part 11), yu must als update yur CT.gv recrds at least every 12 mnths, r within 30 days f a change in recruitment status. 3. When d I have t pst basic results? The law requires that a subset f basic infrmatin be psted n ClinicalTrials.gv fr any study in which the study prduct is apprved fr any use. Fr example, if yu are studying an apprved drug fr a new use, yu must register basic results. Yu must pst this infrmatin within 12 mnths f the Primary Cmpletin Date defined by CT.gv as the final data cllectin pint fr the primary endpint. Please nte that yu may nt wait until cmplete data analysis f yur prject is cmpleted t pst basic results, if such cmpletin falls utside the required time frame. 4. What are the cnsequences if I dn t register? The cnsequences fr nn-cmpliance can include fines frm the FDA r NIH, r the withhlding f grant funds fr yu individually r fr the entire institutin. Other cnsequences include rejectin fr publicatin in tp jurnals (even fr studies nt required by law t register). 5. What Are the Penalties fr Failing t Register? Accrding t the FDA/NIH (Fd and Drug Amendments Act f 2007): Penalties may include civil mnetary penalties up t $10,000 fine fr failing t submit r fr submitting fraudulent infrmatin t ClinicalTrials.gv. After ntificatin f nncmpliance, the fine may g up t $10,000 per day until reslved. Fr federally funded grants, penalties may include the withhlding r recvery f grant funds. 11

12 Accrding t the ICMJE: Unregistered trials will nt be cnsidered fr publicatin in jurnals that adhere t ICMJE standards. This penalty has nt changed ver time. 12