Guidance for Sponsors, 
Clinical Investigators, and 
IRBs 
Data Retention When Subjects 
Withdraw from FDA-Regulated 
Clinical Trials 
 
 
Additional copies are available from: 
 
Good Clinical Practice Program, HF-34  
Office of Science & Health Coordination, Office of the Commissioner  
Food and Drug Administration  
5600 Fishers Lane  
Rockville, MD 20857  
(Tel) (301)-827-3340  
http://www.fda.gov/oc/gcp/draft.html 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Office of the Commissioner (OC) 
Good Clinical Practice Program (GCPP) 
 
                          October 2008
 
   
Contains Nonbinding Recommendations 
 
 
 
 TABLE OF CONTENTS 
 
 
 
I.  INTRODUCTION....................................................................................................................1 
II.  BACKGROUND.....................................................................................................................1 
III.  DISCUSSION........................................................................................................................3 
IV.  FDA POLICY........................................................................................................................5   
Contains Nonbinding Recommendations 
 
1
Guidance for Sponsors, Clinical Investigators, and IRBs  
Data Retention When Subjects Withdraw from FDA-
Regulated Clinical Trials 
 
 
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 appropriate FDA staff.  If you cannot identify the appropriate FDA staff, call the appropriate 
telephone number listed on the title page of this guidance. 
 
 
I.  INTRODUCTION 
 
  This guidance is intended for sponsors, clinical investigators and institutional 
review boards (IRBs).  It describes the Food and Drug Administrations (FDA) 
longstanding policy that already-accrued data, relating to individuals who cease 
participating in a study, are to be maintained as part of the study data.  This pertains to 
data from individuals who decide to discontinue participation in a study, who are 
withdrawn by their legally authorized representative, as applicable, or who are 
discontinued from participation by the clinical investigator.  This policy is supported by 
the statutes and regulations administered by FDA as well as ethical and quality standards 
applicable to clinical research.  Maintenance of these records includes, as with all study 
records, safeguarding the privacy and confidentiality of the subjects information.   
 
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.  BACKGROUND 
 
  The Federal Food, Drug, and Cosmetic Act (the act) authorizes the study of an 
investigational product to develop safety and effectiveness data about the product.  The 
act also requires the maintenance of records documenting these data and the submission 
of certain reports regarding this use to FDA.2, 3  FDA (by delegation from the Secretary) 
                                                 
1 This guidance document was developed by the Good Clinical Practice Program and the 
Office of the Chief Counsel (OCC), both in the Office of the Commissioner (OC), FDA.  
 
2 The investigational new drug provisions of the act condition use of such drugs upon, for 
example, "the establishment and maintenance of such records, and the making of such 
  1  
Contains Nonbinding Recommendations 
 
implemented these provisions by issuing regulations relating to investigational drugs, the 
Investigational New Drug (IND) regulations at 21 CFR Part 312, and investigational 
devices, the Investigational Device Exemptions (IDE) regulations at 21 CFR Part 812.  
These regulations specify that data collection and maintenance are indispensable 
requirements when conducting a clinical investigation of an unapproved product.   
 
  For example, the IND regulations require investigators ... to prepare and 
maintain adequate and accurate case histories that record all observations and other data 
pertinent to the investigation on each individual administered the investigational drug or 
employed as a control in the investigation" (21 CFR 312.62(b)).  Similarly, the IDE 
regulations require an investigator to maintain "Records of each subject's case history and 
exposure to the device" (21 CFR 812.140(a)(3)).   
 
Additionally, the regulations relating to the submission of marketing applications 
require the submission of all relevant data in order for FDA to determine whether a 
product meets the standard for approval.  A new drug application (NDA) must include a 
description and analysis of each clinical pharmacology study and controlled clinical 
study, a description of each uncontrolled trial, and an integrated summary of all available 
information about the safety of the drug product (21 CFR 314.50(d)(5)) and copies of 
individual case report forms for each patient who died during a clinical study or who did 
not complete the study because of an adverse event, whether believed to be drug related 
or not, including patients receiving reference drugs or placebo (21 CFR 314.50(f)(2)).  
Similarly, an application for premarket approval (PMA) for a device must include safety 
and effectiveness data, adverse reactions and complications, patient discontinuation, 
patient complaints, device failures and replacements, tabulations of data from all 
individual subject report forms and copies of such forms for each subject who died during 
a clinical investigation or who did not complete the investigation (21 CFR 
814.20(b)(6)(ii)).  Likewise , an application for a biologics license application (BLA) 
must include data derived from nonclinical laboratory and clinical studies which 
demonstrate that the manufactured product is safe, pure, and potent (21 CFR 601.2(a)).   
 
                                                                                                                                                 
reports to the Secretary, by the manufacturer or the sponsor of the investigation of such 
drug, of data (including but not limited to analytical reports by investigators) obtained as 
the result of such investigational use of such drug, as the Secretary finds will enable him 
to evaluate the safety and effectiveness of such drug in the event of the filing of an 
application pursuant to subsection (b)."  21 USC 355(i)(1)(C).   
 
3 The investigational device provisions similarly require "that the person applying for an 
exemption for a device assure the establishment and maintenance of such records, and the 
making of such reports to the Secretary of data obtained as a result of the investigational 
use of the device during the exemption, as the Secretary determines will enable him to 
assure compliance with such conditions, review the progress of the investigation, and 
evaluate the safety and effectiveness of the device."  21 USC 360j(g)(2)(B)(ii).   
 
  2  
Contains Nonbinding Recommendations 
 
FDA law and regulations require the collection and maintenance of complete 
clinical study data.  This includes information on subjects who withdraw from a clinical 
investigation, whether the subject decides to discontinue participation in the clinical trial 
(21 CFR 50.25(a)(8)) or is discontinued by the investigator because the subject no longer 
qualifies under the protocol (for example, due to a significant adverse event or due to 
failure to cooperate with study requirements).  FDA recognizes that a subject may 
withdraw from a study; however, the withdrawal does not extend to the data already 
obtained during the time the subject was enrolled.  FDAs longstanding policy has been 
that all data collected up to the point of withdrawal must be maintained in the database 
and included in subsequent analyses, as appropriate.4   
 
III.  DISCUSSION 
 
FDA law and regulations recognize that a complete and accurate risk/benefit 
profile of an investigational product depends upon the data from every subjects 
experience in the clinical trial.  For example, if a subjects data could be withdrawn from 
a study, a sponsor would not have access to data on adverse events experienced by the 
subject and would be unable to evaluate whether changes to the protocol or the informed 
consent documents are needed to ensure the rights, safety, and welfare of other trial 
subjects.5   
                                                 
4 FDA previously addressed the topic of data withdrawal in the preamble to the 1996 
final rule providing an exception from informed consent requirements for emergency 
research, 21 CFR 50.24.  In response to a comment that a subjects legally authorized 
representative should be allowed to prevent the review of the subjects data, FDA stated:  
FDA regulations (see, for example, Sec. 312.62 and Sec. 812.140(a)(3)) require 
investigators to prepare and maintain adequate case histories recording all observations 
and other data pertinent to the investigation on each individual treated with the drug or 
exposed to the device. The agency needs all such data in order to be able to determine the 
safety and effectiveness of the drug or device. The fact of having been in an investigation 
cannot be taken back. Also, if a subject were able to control the use (inclusion and 
exclusion) of his or her data, and particularly if the clinical investigation were not 
blinded, the bias potential would be immense. Thus, the agency rejects this comment 
because it could prevent FDA from learning of an important effect of the product and 
significantly bias the results of the investigation (see comment 95, 61 Federal Register 
51498, 51519, October 2, 1996).  It should be appreciated that FDAs response applies to 
the most potentially difficult situation, that is, studies involving an exception from the 
informed consent requirements in which subjects, due to a life threatening medical 
condition, are unable to provide informed consent to participate in the study.  Subjects 
may subsequently withdraw from such studies, but the data collected up to withdrawal 
may not be removed.  
 
5 Such review of safety data by sponsors is required by 21 CFR 312.56 and 21 CFR 
812.46. 
 
  3  
Contains Nonbinding Recommendations 
 
 
The validity of a clinical study would also be compromised by the exclusion of 
data collected during the study.  There is long-standing concern with the removal of data, 
particularly when removal is non-random, a situation called informative censoring.  
FDA has long advised intent-to-treat analyses (analyzing data related to all subjects the 
investigator intended to treat), and a variety of approaches for interpretation and 
imputation of missing data have been developed to maintain study validity.6  Complete 
removal of data, possibly in a non-random or informative way, raises great concerns 
about the validity of the study.   
 
There is particular concern with a studys reliability when subjects withdraw their 
data in a non-random way because they are unhappy with their experience, either because 
they failed to obtain a desired effect or suffered an adverse event.  Loss of these subjects 
data could greatly distort effectiveness results and could hide important safety 
information (for example, toxicity) of a poorly tolerated treatment.  Allowing subjects to 
withdraw data could even provide an opportunity for unscrupulous parties to improve 
study results by selectively encouraging certain subjects to withdraw from a study.   
 
The importance of ensuring the scientific validity of clinical research is reflected 
not only in FDAs regulations but in international documents and published literature as 
well.  The International Conference on Harmonization of Technical Requirements for 
Registration of Pharmaceuticals for Human Use (ICH), in which FDA participates, 
identifies as a principle of good clinical practice that clinical trials should be 
scientifically sound."7  Other international guidance documents include similar 
statements, such as the International Ethical Guidelines for Biomedical Research 
Involving Human Subjects, Guideline 1, which states scientifically invalid research is 
unethical in that it exposes research subjects to risks without possible benefit ...8   
 
Published literature on medical research ethics, dating back to the Nuremburg 
Code of 1947,9 also emphasizes the importance of scientific validity.  As maintained by 
                                                 
6 For a discussion of problems presented by missing data in the analysis of clinical trials, 
please see Points to Consider on Missing Data from the Committee for Proprietary 
Medicinal Products of the European Medicines Agency (EMEA), 
http://www.emea.europa.eu/pdfs/human/ewp/177699EN.pdf.  
7 http://www.fda.gov/cder/guidance/959fnl.pdf.  ICH E6 Guidance for Industry, Good 
Clinical Practice: Consolidated Guidance, adopted as official guidance by FDA, Section 
2.5.  
 
8 http://www.cioms.ch/frame_guidelines_nov_2002.htm.  These guidelines are published 
by the Counsel of International Organizations for Medical Sciences (CIOMS).  Guideline 
11 reiterates this principle.   
 
9 The Nuremberg Code: http://ohsr.od.nih.gov/guidelines/nuremberg.html 
 
  4  
Contains Nonbinding Recommendations 
 
Emanuel, et. al., For a clinical research protocol to be ethical, the methods must be valid 
and practically feasible:  the research must have a clear scientific objective; be designed 
using accepted principles, methods, and reliable practices; have sufficient power to 
definitively test the objective; and offer a plausible data analysis plan.10  The importance 
of scientific validity to ethical research is also underscored in modern ethical documents, 
such as the Declaration of Helsinki11 and the Belmont Report, issued in 1979 by the 
National Commission for the Protection of Human Subjects of Biomedical and 
Behavioral Research.12   
 
In summary, data collected on study subjects up to the time of withdrawal must 
remain in the trial database in order for the study to be scientifically valid.  If a subject 
withdraws from a study, removal of already collected data would undermine the 
scientific, and therefore the ethical, integrity of the research.  Such removal of data could 
also put enrolled subjects, future subjects, and eventual users of marketed products at an 
unreasonable risk.  Finally, removal of data would fundamentally compromise FDAs 
ability to perform its mission, to protect public health and safety by ensuring the safety 
and effectiveness of regulated products.   
 
IV.  FDA POLICY 
 
Following are key points regarding FDAs policy on the withdrawal of subjects 
from a clinical investigation, whether the subject elects to discontinue further 
interventions or the clinical investigator terminates the subjects participation in further 
interventions: 
 
                                                 
10 Emanuel, EJ, Wendler, D, and Grady, C., What Makes Clinical Research Ethical? 
JAMA 283:20 (May 24/31, 2000 2701-11).   
 
11 "Medical research involving human subjects must conform to generally accepted 
scientific principles, be based on a thorough knowledge of the scientific literature, other 
relevant sources of information, and on adequate laboratory and, where appropriate, 
animal experimentation." The Declaration of Helsinki (2000) (as amended 2002, 2004) 
http://www.wma.net/e/policy/b3.htm. 
 
12 The Belmont Report addresses the connection between scientific validity and ethics 
through the Principle of Beneficence.  Beneficence has two complementary aspects: 
maximizing possible benefits and minimizing possible harms.  The Report recognizes as 
one of the components of maximizing benefits, "In the case of scientific research in 
general, members of the larger society are obliged to recognize the longer term benefits 
and risks that may result from the improvement of knowledge and from the development 
of novel medical, psychotherapeutic, and social procedures."  
http://ohsr.od.nih.gov/guidelines/belmont.html 
 
  5  
Contains Nonbinding Recommendations 
 
  According to FDA regulations, when a subject withdraws from a study, the data 
collected on the subject to the point of withdrawal remains part of the study database 
and may not be removed.   
 
  An investigator may ask a subject who is withdrawing whether the subject wishes to 
provide continued follow-up and further data collection subsequent to their 
withdrawal from the interventional portion of the study.  Under this circumstance, the 
discussion with the subject would distinguish between study-related interventions and 
continued follow-up of associated clinical outcome information, such as medical 
course or laboratory results obtained through non-invasive chart review, and address 
the maintenance of privacy and confidentiality of the subjects information.   
 
  If a subject withdraws from the interventional portion of the study, but agrees to 
continued follow-up of associated clinical outcome information as described in the 
previous bullet, the investigator must obtain the subjects informed consent for this 
limited participation in the study (assuming such a situation was not described in the 
original informed consent form).  In accordance with FDA regulations, IRB approval 
of informed consent documents would be required (21 CFR 50.25, 56.109(b), 312.60, 
312.66, 812.100).   
 
  If a subject withdraws from the interventional portion of a study and does not consent 
to continued follow-up of associated clinical outcome information, the investigator 
must not access for purposes related to the study the subjects medical record or other 
confidential records requiring the subjects consent.  However, an investigator may 
review study data related to the subject collected prior to the subjects withdrawal 
from the study, and may consult public records, such as those establishing survival 
status.   
 
  6