Guidance for Industry 
 
Investigator Responsibilities  
Protecting the Rights, Safety, 
and Welfare of Study Subjects  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
Center for Biologics Evaluation and Research (CBER) 
Center for Devices and Radiological Health (CDRH) 
 
Procedural 
October 2009
   
Guidance for Industry 
Investigator Responsibilities  
Protecting the Rights, Safety, 
and Welfare of Study Subjects  
 
 
 
Additional copies are available from: 
Office of Training and Communication 
Division of Drug Information, HFD-240 
Center for Drug Evaluation and Research 
Food and Drug Administration 
 (Tel) 301-827-4573 
 http://www.fda.gov/cder/guidance/index.htm 
or 
 Office of Communication, Training and  
Manufacturers Assistance, HFM-40  
Center for Biologics Evaluation and Research 
 Food and Drug Administration 
 http://www.fda.gov/cber/guidelines.htm.   
(Tel) 800-835-4709 or 301-827-1800 
or 
 Office of Health and Industry Programs 
Division of Small Manufacturers, International, and Consumer Assistance, HFZ-220 
Center for Devices and Radiological Health 
Food and Drug Administration 
Tel: 1-800-638-2041 
www.fda.gov/cdrh 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
Center for Biologics Evaluation and Research (CBER) 
Center for Devices and Radiological Health (CDRH) 
 
Procedural 
October 2009 
 
  Contains Nonbinding Recommendations 
 
 
TABLE OF CONTENTS 
 
I.  INTRODUCTION..............................................................................................................................................1 
II.  OVERVIEW OF INVESTIGATOR RESPONSIBILITIES..........................................................................1 
III.  CLARIFICATION OF CERTAIN INVESTIGATOR RESPONSIBILITIES........................................2 
A.  SUPERVISION OF THE CONDUCT OF A CLINICAL INVESTIGATION.....................................................................2 
1.  What Is Appropriate Delegation of Study-Related Tasks?.........................................................................3 
2.  What Is Adequate Training?.......................................................................................................................4 
3.  What Is Adequate Supervision of the Conduct of an Ongoing Clinical Trial?...........................................4 
4.  What Are an Investigators Responsibilities for Oversight of Other Parties Involved in the Conduct of a 
Clinical Trial?......................................................................................................................................................5 
B.  PROTECTING THE RIGHTS, SAFETY, AND WELFARE OF STUDY SUBJECTS........................................................7 
1.  Reasonable Medical Care Necessitated by Participation in a Clinical Trial.............................................7 
2.  Reasonable Access to Medical Care...........................................................................................................7 
3.  Protocol Violations that Present Unreasonable Risks................................................................................8 
ATTACHMENT A:  COPY OF FORM 1572...........................................................................................................9 
ATTACHMENT B:  INVESTIGATOR RESPONSIBILITIES............................................................................12 
  Contains Nonbinding Recommendations 
 
1
Guidance for Industry  
Investigator ResponsibilitiesProtecting the Rights, Safety, and Welfare 
of Study Subjects 
 
 
This guidance represents the Food and Drug Administration's (FDA's) current thinking on this topic.  It does not 
create or confer any rights for or on any person and does not operate to bind FDA or the public.  You can use an 
alternative approach if the approach satisfies the requirements of the applicable statutes and regulations. If you want 
to discuss an alternative approach, contact the FDA staff responsible for implementing this guidance.  If you cannot 
identify the appropriate FDA staff, call the appropriate number listed on the title page of this guidance.  
 
 
 
I.  INTRODUCTION  
 
This guidance provides an overview of the responsibilities of a person who conducts a clinical 
investigation of a drug, biological product, or medical device (an investigator as defined in 21 CFR 
312.3(b) and 21 CFR 812.3(i)).  The goal of this guidance is to help investigators better meet their 
responsibilities with respect to protecting human subjects and ensuring the integrity of the data from 
clinical investigations. This guidance is intended to clarify for investigators and sponsors FDAs 
expectations concerning the investigators responsibility (1) to supervise a clinical study in which some 
study tasks are delegated to employees or colleagues of the investigator or other third parties and (2) to 
protect the rights, safety, and welfare of study subjects.  
  
FDA's guidance documents, including this guidance, do not establish legally enforceable responsibilities.  
Instead, guidances describe the Agency's current thinking on a topic and should be viewed only as 
recommendations, unless specific regulatory or statutory requirements are cited.  The use of the word 
should in Agency guidances means that something is suggested or recommended, but not required.  
 
 
II.  OVERVIEW OF INVESTIGATOR RESPONSIBILITIES 
  
In conducting clinical investigations of drugs, including biological products, under 21 CFR part 312 and 
of medical devices under 21 CFR part 812, the investigator is responsible for: 
 
  Ensuring that a clinical investigation is conducted according to the signed investigator statement 
for clinical investigations of drugs, including biological products, or agreement for clinical 
investigations of medical devices, the investigational plan, and applicable regulations 
  Protecting the rights, safety, and welfare of subjects under the investigators care 
  Controlling drugs, biological products, and devices under investigation (21 CFR 312.60, 21 CFR 
812.100)   
 
                                                 
1 This guidance has been prepared by the Investigator Responsibilities Working Group, which includes representatives from the 
Office of the Commissioner, the Center for Drug Evaluation and Research (CDER), the Center for Biologics Evaluation and 
Research (CBER), and the Center for Devices and Radiological Health (CDRH) at the Food and Drug Administration.   
  1 Contains Nonbinding Recommendations 
 
Although specific investigator responsibilities in drug and biologics clinical trials are not identical to the 
investigator responsibilities in medical device clinical trials, the general responsibilities are essentially the 
same.  This guidance discusses the general investigator responsibilities that are applicable to clinical trials 
of drugs, biologics, and medical devices.   
   
An investigators responsibilities in conducting clinical investigations of drugs or biologics are provided 
in 21 CFR Part 312. Many of these responsibilities are included in the required investigators signed 
statement, Form FDA-1572 (see Attachment A) (hereinafter referred to as 1572).  Note that although the 
1572 specifically incorporates most of the requirements directed at investigators in part 312, not all 
requirements are listed in the 1572. Investigators and sponsors should refer to 21 CFR Parts 11, 50, 54, 
56, and 312 for a more comprehensive listing of FDA's requirements for the conduct of drug and 
biologics studies.2 
 
An investigators responsibilities in conducting clinical investigations of a medical device are  provided in 
21 CFR Part 812, including the requirement that there be a signed agreement between the investigator and 
sponsor (see 21 CFR 812.43(c)(4) and 812.100).  The medical device regulations do not require use of a 
specific form for an investigators statement; and there are additional requirements not listed above (see 
Attachment B).  Investigators and sponsors should refer to 21 CFR Parts 11, 50, 54, 56, and 812 for a 
more comprehensive listing of FDA's requirements for the conduct of device studies. 
 
Nothing in this guidance is intended to conflict with recommendations for investigators contained in the 
International Conference on Harmonisation (ICH) guidance for industry, E6 Good Clinical Practice: 
Consolidated Guidance (Good Clinical Practice Guidance).3  
 
 
III.  CLARIFICATION OF CERTAIN INVESTIGATOR RESPONSIBILITIES 
 
This section of the guidance clarifies the investigators responsibility  to supervise the conduct of the 
clinical investigation and  to protect the rights, safety, and welfare of participants in drug and medical 
device clinical trials. 
        
A.  Supervision of the Conduct of a Clinical Investigation 
  
As stated above, investigators who conduct clinical investigations of drugs, including biological products, 
under 21 CFR Part 312, commit themselves to personally conduct or supervise the investigation. 
Investigators who conduct clinical investigations of medical devices, under 21 CFR Part 812, commit 
themselves to supervise all testing of the device involving human subjects. It is common practice for 
investigators to delegate certain study-related tasks to employees, colleagues, or other third parties 
(individuals or entities not under the direct supervision of the investigator).  When tasks are delegated by 
an investigator, the investigator is responsible for providing adequate supervision of those to whom tasks 
are delegated.  The investigator is accountable for regulatory violations resulting from failure to 
adequately supervise the conduct of the clinical study. 
                                                 
2
 As a reminder, some investigators may be responsible for submitting certain clinical trial information to the National 
Institutes of Health clinical trials data bank under 42 U.S.C 282(j), 402(j) of the Public Health Service Act. Although not all 
investigators will be expected to meet this requirement, go to www.clinicaltrials.gov for further information about potential 
responsibilities. 
3 Guidances, including ICH guidances, are available on the Agencys Web page.  See the Web addresses on the second title 
page of this guidance. 
  2 Contains Nonbinding Recommendations 
 
 
In assessing the adequacy of supervision by an investigator, FDA focuses on four major areas:  (1) 
whether individuals who were delegated tasks were qualified to perform such tasks, (2) whether study 
staff received adequate training on how to conduct the delegated tasks and were provided with an 
adequate understanding of the study, (3) whether there was adequate supervision and involvement in the 
ongoing conduct of the study, and (4) whether there was adequate supervision or oversight of any third 
parties involved in the conduct of a study to the extent such supervision or oversight was reasonably 
possible.      
   
1.  What Is Appropriate Delegation of Study-Related Tasks? 
 
The investigator should ensure that any individual to whom a task is delegated is qualified by 
education, training, and experience (and state licensure where relevant) to perform the delegated 
task.  Appropriate delegation is primarily an issue for tasks considered to be clinical or medical in 
nature, such as evaluating study subjects to assess clinical response to an investigational therapy 
(e.g., global assessment scales, vital signs) or providing medical care to subjects during the course 
of the study.  Most clinical/medical tasks require formal medical training and may also have 
licensing or certification requirements.  Licensing requirements may vary by jurisdiction (e.g., 
states, countries).  Investigators should take such qualifications/licensing requirements into 
account when considering delegation of specific tasks.  In all cases, a qualified physician (or 
dentist) should be responsible for all trial-related medical (or dental) decisions and care.4  
 
During inspections of investigation sites, FDA has identified instances in which study tasks have 
been delegated to individuals lacking appropriate qualifications.  Examples of tasks that have been 
inappropriately delegated include:  
  Screening evaluations, including obtaining medical histories and assessment of 
inclusion/exclusion criteria 
  Physical examinations 
  Evaluation of adverse events 
  Assessments of primary study endpoints  
  Obtaining informed consent 
 
The investigator is responsible for conducting studies in accordance with the protocol (see 21 CFR 
312.60, Form FDA-1572, 21 CFR 812.43 and 812.100).  In some cases a protocol may specify the 
qualifications of the individuals who are to perform certain protocol-required tasks (e.g., 
physician, registered nurse), in which case the protocol must be followed even if state law permits 
individuals with different qualifications to perform the task (see 21 CFR 312.23(a)(6) and 
312.40(a)(1)).  For example, if the state in which the study site is located permits a nurse 
practitioner or physicians assistant to perform physical examinations under the supervision of a 
physician, but the protocol specifies that physical examinations must be done by a physician, a 
physician must perform such exams.  
 
The investigator should maintain a list of the appropriately qualified persons to whom significant 
trial-related duties have been delegated.5  This list should also describe the delegated tasks, 
identify the training that individuals have received that qualifies them to perform delegated tasks 
                                                 
4 Guidance for industry, E6 Good Clinical Practice: Consolidated Guidance, section 4.3.1. 
5 Ibid, section 4.1.5 
  3 Contains Nonbinding Recommendations 
 
(e.g., can refer to an individuals CV on file), and identify the dates of involvement in the study.  
An investigator should maintain separate lists for each study conducted by the investigator. 
 
2.  What Is Adequate Training? 
 
The investigator should ensure that there is adequate training for all staff participating in the 
conduct of the study, including any new staff hired after the study has begun to meet unanticipated 
workload or to replace staff who have left.  The investigator should ensure that staff:   
  Are familiar with the purpose of the study and the protocol 
  Have an adequate  understanding of the specific details of the protocol and attributes of the 
investigational product needed to perform their assigned tasks 
  Are aware of regulatory requirements and acceptable standards for the conduct of clinical 
trials and the protection of human subjects 
  Are competent to perform or have been trained to perform the tasks they are delegated 
  Are informed of any pertinent changes during the conduct of the trial and receive  
additional training as appropriate 
 
If the sponsor provides training for investigators in the conduct of the study, the investigator 
should ensure that staff receive the sponsors training, or any information (e.g., training materials) 
from that training that is pertinent to the staff's role in the study.  
 
3.  What Is Adequate Supervision of the Conduct of an Ongoing Clinical Trial? 
 
For each study site, there should be a distinct individual identified as an investigator who has 
supervisory responsibility for the site.  Where there is a subinvestigator at a site, that individual 
should report directly to the investigator for the site (i.e., the investigator should have clear 
responsibility for evaluating the subinvestigators performance and the authority to terminate the 
subinvestigators involvement with the study) and the subinvestigator should not be delegated the 
primary supervisory responsibility for the site. 
 
The investigator should have sufficient time to properly conduct and supervise the clinical trial.  
The level of supervision should be appropriate to the staff, the nature of the trial, and the subject 
population.  In FDAs experience, the following factors may affect the ability of an investigator to 
provide adequate supervision of the conduct of an ongoing clinical trial at the investigators site: 
  Inexperienced study staff 
  Demanding workload for study staff 
  Complex clinical trials (e.g., many observations, large amounts of data collected) 
  Large number of subjects enrolled at a site 
  A subject population that is seriously ill 
  Conducting multiple studies concurrently 
  Conducting a study from a remote (e.g., off-site) location 
  Conducting a study at multiple sites under the oversight of a single investigator, 
particularly where those sites are not in close proximity    
 
The investigator should develop a plan for the supervision and oversight of the clinical trial at the 
site.  Supervision and oversight should be provided even for individuals who are highly qualified 
  4 Contains Nonbinding Recommendations 
 
and experienced.  A plan might include the following elements, to the extent they apply to a 
particular trial: 
 
  Routine meetings with staff to review trial progress, adverse events, and update staff on 
any changes to the protocol or other procedures 
  Routine meetings with the sponsors monitors 
  A procedure for the timely correction and documentation  of problems identified by study 
personnel, outside monitors or auditors, or other parties involved in the conduct of a study 
  A procedure for documenting or reviewing the performance of delegated tasks in a 
satisfactory and timely manner (e.g., observation of the performance of selected 
assessments or independent verification by repeating selected assessments) 
  A procedure for ensuring that the consent process is being conducted in accordance with 
21 CFR Part 50 and that study subjects understand the nature of their participation and the 
risks 
  A procedure for ensuring that source data are accurate, contemporaneous, and original 
  A procedure for ensuring that information in source documents is accurately captured on 
the case report forms (CRFs) 
  A procedure for dealing with data queries and discrepancies identified by the study 
monitor 
  Procedures for ensuring study staff comply with the protocol and adverse event assessment 
and reporting requirements  
  A procedure for addressing medical and ethical issues that arise during the course of the 
study in a timely manner  
 
4.  What Are an Investigators Responsibilities for Oversight of Other Parties Involved in the 
Conduct of a Clinical Trial? 
 
a.     Study Staff Not in the Direct Employ of the Investigator 
   
Staff involved directly in the conduct of a clinical investigation may include individuals 
who are not in the direct employ of the investigator.  For example, a site management 
organization (SMO) may hire an investigator to conduct a study and provide the 
investigator with a study coordinator or nursing staff employed by the SMO.  In this 
situation, the investigator should take steps to ensure that the staff not under his/her direct 
employ are qualified to perform delegated tasks (see section III.A.1) and have received 
adequate training on carrying out the delegated tasks and on the nature of the study (see 
section III.A.2), or the investigator should provide such training.  The investigator should 
be particularly cautious where documentation needed to comply with the investigators 
regulatory responsibilities is developed and maintained by SMO staff (e.g., source 
documents, CRFs, drug storage and accountability records, institutional review board  
correspondence).  A sponsor who retains an SMO shares responsibility for the quality of 
the work performed by the SMO. 
 
The investigator is responsible for supervising the study tasks performed by this staff, even 
though they are not in his/her direct employ during the conduct of the study (see section 
III.A.3).  This responsibility exists regardless of the qualifications and experience of staff 
members. In the event that the staffs performance of study-related tasks is not adequate 
  5 Contains Nonbinding Recommendations 
 
and cannot be made satisfactory by the investigator, the investigator should document the 
observed deficiencies in writing to the staff members supervisor(s) and inform the 
sponsor.  Depending on the severity of the deficiencies, the clinical trial may need to be 
voluntarily suspended until personnel can be replaced.     
 
b.  Parties Other than Study Staff  
 
There are often critical aspects of a study performed by parties not involved directly in 
patient care or contact and not under the direct control of the clinical investigator.  For 
example, clinical chemistry testing, radiologic assessments, and electrocardiograms are 
commonly done by a central independent facility retained by the sponsor.  Under these 
arrangements, the central facility usually provides the test results directly to the sponsor 
and to the investigator.  Because the activities of these parties are critical to the outcome of 
the study and because the sponsor retains the services of the facility, the sponsor is 
responsible for ensuring that these parties are competent to fulfill and are fulfilling their 
responsibilities to the study. 
 
Less frequently, a study may require that investigators arrange to obtain information 
critical to the study that cannot be obtained at the investigators site.  For example, if the 
study protocol requires testing with special equipment or expertise not available at the 
investigators site, the investigator might make arrangements for an outside facility to 
perform the test.  In this case, the results are usually provided directly to the investigator, 
who then submits the information to the sponsor.  If the investigator retains the services of 
a facility to perform study assessments, the investigator should take steps to ensure that the 
facility is adequate (e.g., has the required certification or licenses).  The investigator may 
also institute procedures to ensure the integrity of data and records obtained from the 
facility providing the information (e.g., a process to ensure that records identified as 
coming from the facility are authentic and accurate). Procedures are particularly important 
when assessments are crucial to the evaluation of the efficacy or safety of an intervention 
or to the decision to include or exclude subjects who would be exposed to unreasonable 
risk. 
 
Investigators should carefully review the reports from these external sources for results that 
are inconsistent with clinical presentation.  To the extent feasible, and considering the 
specifics of study design, investigators should evaluate whether results appear reasonable, 
individually, and in aggregate, and they should document the evaluation.  If investigators 
detect possible errors or suspect that results from a central laboratory or testing facility 
might be questionable, the investigator should contact the sponsor immediately. 
 
c.  Special Considerations for Medical Device Studies 
 
Field clinical engineers (device sponsor employees) have traditionally played a role in 
some investigational device procedures (e.g., cardiology, orthopedics, and ophthalmology) 
by providing technical assistance to the device investigator.  The field clinical engineer 
should be supervised by the investigator because the field clinical engineers presence or 
activities may have the potential to bias the outcome of studies, may affect the quality of 
research data, and/or may compromise the rights and welfare of human subjects.  The field 
clinical engineers activities should be described in the protocol.  If the field engineer has 
  6 Contains Nonbinding Recommendations 
 
face-to-face contact with subjects or if the activities of the field engineer directly affect the 
subject, those activities should also be described in the informed consent.  
 
B.  Protecting the Rights, Safety, and Welfare of Study Subjects 
 
Investigators are responsible for protecting the rights, safety, and welfare of subjects under their care 
during a clinical trial (21 CFR 312.60 and 812.100).  This responsibility should include:  
  Providing reasonable medical care for study subjects for medical problems arising during 
participation in the trial that are, or could be, related to the study intervention 
  Providing reasonable access to needed medical care, either by the investigator or by another 
identified, qualified individual (e.g., when the investigator is unavailable, when specialized care is 
needed) 
  Adhering to the protocol so that study subjects are not exposed to unreasonable risks  
 
The investigator should inform the subject's primary physician about the subject's participation in the trial 
if the subject has a primary physician and the subject agrees to the primary physician being informed. 
  
1.  Reasonable Medical Care Necessitated by Participation in a Clinical Trial 
 
During a subject's participation in a trial, the investigator (or designated subinvestigator) should 
ensure that reasonable medical care is provided to a subject for any adverse events, including 
clinically significant laboratory values, related to the trial participation.  If the investigator does 
not possess the expertise necessary to provide the type of medical care needed by a subject, the 
investigator should make sure that the subject is able to obtain the necessary care from a qualified 
practitioner. For example, if the study involves placement of a carotid stent by an interventional 
neuroradiologist and the subject suffers a cerebral stroke, the neuroradiologist should assess the 
clinical status of the subject and arrange for further care of the subject by a neurologist.  Subjects 
should receive appropriate medical evaluation and treatment until resolution of any emergent 
condition related to the study intervention that develops during or after the course of their 
participation in a study, even if the follow-up period extends beyond the end of the study at the 
investigative site. 
 
The investigator should also inform a subject when medical care is needed for conditions or 
illnesses unrelated to the study intervention or the disease or condition under study when such 
condition or illness is readily apparent or identified through the screening procedures and 
eligibility criteria for the study.  For example, if the investigator determines that the subject has 
had an exacerbation of an existing condition unrelated to the investigational product or the disease 
or condition under study, the investigator should inform the subject.  The subject should also be 
advised to seek appropriate care from the physician who was treating the illness prior to the study, 
if there is one, or assist the subject in obtaining needed medical care.   
 
2.  Reasonable Access to Medical Care 
 
Investigators should be available to subjects during the conduct of the trial for medical care related 
to participation in the study.  Availability is particularly important when subjects are receiving a 
drug that has significant toxicity or abuse potential.  For example, if a study drug has potentially 
fatal toxicity, the investigator should be readily available by phone or other electronic 
communication 24 hours a day and in reasonably close proximity to study subjects (e.g., not in 
  7 Contains Nonbinding Recommendations 
 
another state or on prolonged travel).  Study subjects should be clearly educated on the possible 
need for such contact and on precisely how to obtain it, generally by providing pertinent phone 
numbers, e-mail addresses, and other contact information, in writing.  Prior to undertaking the 
conduct of a study, prospective investigators should consider whether they can be available to the 
extent needed given the nature of the trial.   
 
During any period of unavailability, the investigator should delegate responsibility for medical 
care of study subjects to a specific qualified physician who will be readily available to subjects 
during that time (in the manner a physician would delegate responsibility for care in clinical 
practice).  If the investigator is a non-physician, the investigator should make adequate provision 
for any necessary medical care that the investigator is not qualified to provide. 
  
3.  Protocol Violations that Present Unreasonable Risks 
 
There are occasions when a failure to comply with the protocol may be considered a failure to 
protect the rights, safety, and welfare of subjects because the non-compliance exposes subjects to 
unreasonable risks.  For example, failure to adhere to inclusion/exclusion criteria that are 
specifically intended to exclude subjects for whom the study drug or device poses unreasonable 
risks (e.g., enrolling a subject with decreased renal function in a trial in which decreased function 
is exclusionary because the drug may be nephrotoxic) may be considered failure to protect the 
rights, safety, and welfare of the enrolled subject.  Similarly, failure to perform safety assessments 
intended to detect drug toxicity within protocol-specified time frames (e.g., CBC for an oncology 
therapy that causes neutropenia) may be considered failure to protect the rights, safety, and 
welfare of the enrolled subject.  Investigators should seek to minimize such risks by adhering 
closely to the study protocol. 
 
  8 Contains Nonbinding Recommendations 
 
 
ATTACHMENT A:  COPY OF FORM 1572 
 
 
DEPARTMENT OF HEALTH AND HUMAN SERVICES  Form Approved: OMB No. 0910-0014. 
FOOD AND DRUG ADMINISTRATION  Expiration Date: May 31, 2009. 
 
  See OMB Statement on Reverse.
STATEMENT OF INVESTIGATOR 
NOTE: No investigator may participate in 
(TITLE 21, CODE OF FEDERAL REGULATIONS (CFR) PART 312)  an investigation until he/she provides the 
(See instructions on reverse side.)  sponsor with a completed, signed 
Statement of Investigator, Form FDA 1572 
(21 CFR 312.53(c)). 
1.  NAME AND ADDRESS OF INVESTIGATOR 
      
2.  EDUCATION, TRAINING, AND EXPERIENCE THAT QUALIFIES THE INVESTIGATOR AS AN EXPERT IN THE CLINICAL INVESTIGATION OF THE
  DRUG FOR THE USE UNDER INVESTIGATION. ONE OF THE FOLLOWING IS ATTACHED.
 
 CURRICULUM VITAE   OTHER STATEMENT OF QUALIFICATIONS
3.   NAME AND ADDRESS OF ANY MEDICAL SCHOOL, HOSPITAL OR OTHER RESEARCH 
FACILITY WHERETHECLINICALINVESTIGATION(S) WILL BECONDUCTED
      
4.  NAME AND ADDRESS OF ANY CLINICAL LABORATORY FACILITIES TO BEUSED IN THE STUDY.
      
5.  NAME AND ADDRESS OF THE INSTITUTIONAL REVIEW BOARD (IRB) THAT IS RESPONSIBLE FOR REVIEW AND APPROVAL OF THE 
      
6.  NAMES OF THE SUBINVESTIGATORS (e.g., research fellows, residents, associates) WHO WILL BE ASSISTING THE INVESTIGATOR IN THE
  CONDUCT OF THE INVESTIGATION(S). 
      
7.  NAME AND CODE NUMBER, IF ANY, OF THE PROTOCOL(S) IN THE IND FOR THE STUDY(IES) TO BE CONDUCTED BY THE INVESTIGATOR.
      
  9 Contains Nonbinding Recommendations 
 
 
8.  ATTACH THE FOLLOWING CLINICAL PROTOCOL INFORMATION: 
     FOR PHASE 1 INVESTIGATIONS, A GENERAL OUTLINE OF THE PLANNED INVESTIGATION INCLUDING THE ESTIMATED 
DURATION OF  
      THE STUDY AND THE MAXIMUM NUMBER OF SUBJECTS THAT WILL BE INVOLVED. 
     FOR PHASE 2 OR 3 INVESTIGATIONS, AN OUTLINE OF THE STUDY PROTOCOL INCLUDING AN APPROXIMATION OF THE 
NUMBER OF       SUBJECTS TO BE TREATED WITH THE DRUG AND THE NUMBER TO BE EMPLOYED AS 
CONTROLS, IF ANY; THE CLINICAL USES TO BE      INVESTIGATED; CHARACTERISTICS OF SUBJECTS BY AGE, SEX, 
AND CONDITION; THE KIND OF CLINICAL OBSERVATIONS AND         LABORATORY TESTS TO BE 
CONDUCTED; THE ESTIMATED DURATION OF THE STUDY; AND COPIES OR A DESCRIPTION OF CASE       REPORT 
 
FORMS TO BE USED.
9.  COMMITMENTS: 
I agree to conduct the study(ies) in accordance with the relevant, current protocol(s) and will only make changes in a protocol after notifying 
the sponsor, except when necessary to protect the safety, rights, or welfare of subjects. 
I agree to personally conduct or supervise the described investigation(s). 
I agree to inform any patients, or any persons used as controls, that the drugs are being used for investigational purposes and I will 
ensure 
that the requirements relating to obtaining informed consent in 21 CFR Part 50 and institutional review board (IRB) review and approval 
in 21 CFR Part 56 are met. 
I agree to report to the sponsor adverse experiences that occur in the course of the investigation(s) in accordance with 21 CFR 312.64. 
I have read and understand the information in the investigators brochure, including the potential risks and side effects of the drug. 
I agree to ensure that all associates, colleagues, and employees assisting in the conduct of the study(ies) are informed about their 
obligations  
in meeting the above commitments. 
I agree to maintain adequate and accurate records in accordance with 21 CFR 312.62 and to make those records available for 
inspection in accordance with 21 CFR 312.68. 
I will ensure that an IRB that complies with the requirements of 21 CFR Part 56 will be responsible for the initial and continuing review 
and approval of the clinical investigation. I also agree to promptly report to the IRB all changes in the research activity and all 
unanticipated  
problems involving risks to human subjects or others. Additionally, I will not make any changes in the research without IRB approval, 
except where necessary to eliminate apparent immediate hazards to human subjects. 
I agree to comply with all other requirements regarding the obligations of clinical investigators and all other pertinent requirements in 21 
CFR 
 
Part 312.
INSTRUCTIONS FOR COMPLETING FORM FDA 1572 
STATEMENT OF INVESTIGATOR: 
1. Complete all sections. Attach a separate page if additional space is needed. 
2. Attach curriculum vitae or other statement of qualifications as described in Section 2. 
3. Attach protocol outline as described in Section 8. 
4. Sign and date below. 
5. FORWARD THE COMPLETED FORM AND ATTACHMENTS TO THE SPONSOR. The sponsor will incorporate 
  this information along with other technical data into an Investigational New Drug Application (IND). 
  INVESTIGATORS SHOULD NOT SEND THIS FORM DIRECTLY TO THE FOOD AND DRUG ADMINISTRATION. 
10.  SIGNATURE OF INVESTIGATOR  11.  DATE
        
(WARNING: A willfully false statement is a criminal offense. U.S.C. Title 18, Sec. 1001.) 
Public reporting burden for this collection of information is estimated to average 100 hours per response, including the time for reviewing instructions, 
searching existing data sources, gathering and maintaining the data needed, and completing reviewing the collection of information. Send comments 
regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to: 
  10 Contains Nonbinding Recommendations 
 
Department of Health and Human Services  Department of Health and Human Services  "An agency may not conduct or 
Food and Drug Administration  Food and Drug Administration  sponsor,  and  a  person  is  not 
Center for Drug Evaluation and Research  Center for Biologics Evaluation and Research (HFM-99)  required  to  respond  to,  a 
Central Document Room  1401 Rockville Pike  collection of information unless it 
5901-B Ammendale Road  Rockville, MD 20852-1448  displays  a  currently  valid  OMB 
Beltsville, MD  20705-1266  control number." 
Please DO NOT RETURN this application to this address. 
 
  11 Contains Nonbinding Recommendations 
 
ATTACHMENT B:  INVESTIGATOR RESPONSIBILITIES  
 
FOR SIGNIFICANT RISK DEVICE INVESTIGATIONS 
 
 
This document is intended to assist investigators in identifying and complying with their 
responsibilities in connection with the conduct of clinical investigations involving medical 
devices.  Although this guidance primarily addresses duties imposed upon clinical investigators 
by regulations of the Food and Drug Administration (FDA), investigators should be cognizant of 
additional responsibilities that may derive from other sources (such as the study protocol itself, 
the investigator agreement, any conditions of approval imposed by FDA or the governing 
institutional review board, as well as institutional policy and state law).  
 
GENERAL RESPONSIBILITIES OF INVESTIGATORS (21 CFR 812.100) 
 
1.  Ensuring that the investigation is conducted according to the signed agreement, the 
investigational plan, and applicable FDA regulations 
 
2.  Protecting the rights, safety, and welfare of subjects under the investigator's care 
 
3.  Controlling devices under investigation 
 
4.  Ensuring that informed consent is obtained from each subject in accordance with 21 CFR 
Part 50 and that the study is not commenced until FDA and IRB approvals have been 
obtained. 
 
SPECIFIC RESPONSIBILITIES OF INVESTIGATORS (21 CFR 812.110) 
 
1.  Awaiting IRB approval and any necessary FDA approval before requesting written 
informed consent or permitting subject participation 
 
2.  Conducting the investigation in accordance with: 
  a.  The signed agreement with the sponsor 
  b.  The investigational plan  
  c.  The regulations set forth in 21 CFR Part 812 and all other applicable FDA 
regulations 
  d.  Any conditions of approval imposed by an IRB or FDA 
 
  12 Contains Nonbinding Recommendations 
 
3.  Supervising the use of the investigational device.  An investigator shall permit an 
investigational device to be used only with subjects under the investigator's supervision.  
An investigator shall not supply an investigational device to any person not authorized 
under 21 CFR Part 812 to receive it. 
 
4.  Disposing of the device properly.  Upon completion or termination of a clinical 
investigation or the investigator's part of an investigation, or at the sponsor's request, an 
investigator shall return to the sponsor any remaining supply of the device or otherwise 
dispose of the device as the sponsor directs.  
 
MAINTAINING RECORDS (21 CFR 812.140) 
 
An investigator shall maintain the following accurate, complete, and current records relating to 
the investigator's participation in an investigation: 
 
1.  Correspondence with another investigator, an IRB, the sponsor, a monitor, or FDA 
 
2.  Records of receipt, use or disposition of a device that relate to: 
a.  The type and quantity of the device, dates of receipt, and batch numbers or code 
marks 
b.  Names of all persons who received, used, or disposed of each device 
c.  The number of units of the device returned to the sponsor, repaired, or otherwise 
disposed of, and the reason(s) therefore 
 
3.  Records of each subject's case history and exposure to the device, including: 
a.  Documents evidencing informed consent and, for any use of a device by the 
investigator without informed consent, any written concurrence of a licensed 
physician and a brief description of the circumstances justifying the failure to obtain 
informed consent 
b.  All relevant observations, including records concerning adverse device effects 
(whether anticipated or not), information and data on the condition of each subject 
upon entering, and during the course of, the investigation, including information 
about relevant previous medical history and the results of all diagnostic tests; 
c.  A record of the exposure of each subject to the investigational device, including the 
date and time of each use, and any other therapy. 
 
4.  The protocol, with documents showing the dates of and reasons for each deviation from 
the protocol 
 
5.  Any other records that FDA requires to be maintained by regulation or by specific 
requirement for a category of investigations or a particular investigation 
 
 
INSPECTIONS (21 CFR 812.145) 
 
Investigators are required to permit FDA to inspect and copy any records pertaining to the 
investigation including, in certain situations, those which identify subjects.  
 
  13 Contains Nonbinding Recommendations 
 
SUBMITTING REPORTS (21 CFR 812.150) 
 
An investigator shall prepare and submit the following complete, accurate, and timely reports: 
1.  To the sponsor and the IRB: 
  Any unanticipated adverse device effect occurring during an investigation. (Due 
no later than 10 working days after the investigator first learns of the effect.) 
  Progress reports on the investigation. (These reports must be provided at regular 
intervals, but in no event less often than yearly. If there is a study monitor, a copy 
of the report should also be sent to the monitor.) 
  Any deviation from the investigational plan made to protect the life or physical 
well-being of a subject in an emergency. (Report is due as soon as possible but no 
later than 5 working days after the emergency occurs. Except in emergency 
situations, a protocol deviation requires prior sponsor approval; and if the 
deviation may affect the scientific soundness of the plan or the rights, safety, or 
welfare of subjects, prior FDA and IRB approval are required.) 
  Any use of the device without obtaining informed consent. (Due within 5 working 
days after such use.) 
  A final report. (Due within 3 months following termination or completion of the 
investigation or the investigator's part of the investigation. For additional 
guidance, see the discussion under the section entitled "Annual Progress Reports 
and Final Reports.") 
  Any further information requested by FDA or the IRB about any aspect of the 
investigation.     
 
2.  To the Sponsor: 
  Withdrawal of IRB approval of the investigator's part of an investigation. (Due 
within 5 working days of such action). 
 
 
 
INVESTIGATIONAL DEVICE DISTRIBUTION AND TRACKING 
 
The IDE regulations prohibit an investigator from providing an investigational device to any 
person not authorized to receive it (21 CFR 812.110(c)).  The best strategy for reducing the risk 
that an investigational device could be improperly dispensed (whether purposely or 
inadvertently) is for the sponsor and the investigators to closely monitor the shipping, use, and 
final disposal of devices.  Upon completion or termination of a clinical investigation (or the 
investigator's part of an investigation), or at the sponsor's request, an investigator is required to 
return to the sponsor any remaining supply of the device or otherwise to dispose of the device as 
the sponsor directs (21 CFR 812.110(e)).  Investigators must also maintain complete, current, 
and accurate records of the receipt, use, or disposition of investigational devices (21 CFR 
812.140(a)(2)).  Specific recordkeeping requirements are set forth at 21 CFR 812.140(a). 
 
PROHIBITION OF PROMOTION AND OTHER PRACTICES (21 CFR  
812.7)  
  14 Contains Nonbinding Recommendations 
 
 
The IDE regulations prohibit the promotion and commercialization of a device that has not been 
first cleared or approved for marketing by FDA.  This prohibition is applicable to sponsors and 
investigators (or any person acting on behalf of a sponsor or investigator) and encompasses the 
following activities: 
 
1.  Promotion or test marketing of the investigational device 
 
2.  Charging subjects or investigators for the device a price larger than is necessary to 
recover the costs of manufacture, research, development, and handling 
 
3.  Prolonging an investigation beyond the point needed to collect data required to determine 
whether the device is safe and effective 
 
4.  Representing that the device is safe or effective for the purposes for which it is being 
investigated 
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