SOP-309
Participant Retention, Withdrawal and Lost to Follow-Up
- Number
- SOP-309
- Category
- Study Conduct
- Edition
- Reference Edition 1.3
- Approx. pages
- 5
[YELLOW] the site fills in. [DEFAULT: green] a value the site may keep or change.
On this page
1. Purpose
This SOP describes how [SITE NAME] keeps participants engaged through the end of a study, handles a participant's decision to stop treatment or leave the study, withdraws participants when the investigator decides to, and documents attempts to reach participants who stop attending.
2. Scope
This SOP applies to all enrolled participants in every study at [SITE NAME], from enrollment to the protocol-defined end of participation.
Out of scope: recruitment before consent (SOP-300); the consent process itself (SOP-301); participant payments (SOP-310); remote and home visits (SOP-313).
Where the protocol, sponsor or IRB sets a stricter requirement than this SOP, the stricter requirement applies.
3. Responsibilities
| Role | Responsibilities |
|---|---|
| Principal Investigator (PI) | Approves the study retention plan. Decides on investigator-initiated withdrawal and discontinuation of IP. Arranges safety follow-up and medical care for participants who stop. Confirms lost to follow-up status. |
| Sub-Investigator (Sub-I) | Discusses discontinuation and withdrawal with participants where delegated and records the medical assessment. |
| Clinical Research Coordinator (CRC) | Schedules visits within windows, sends reminders, keeps F-309-01, documents withdrawal discussions and contact attempts, and updates EDC and IRT. |
| Lead CRC | Prepares the retention plan, monitors visit adherence and missed visits, and reports retention risks to the PI. |
| Recruitment Specialist | Where used, supports retention contacts and community outreach under the retention plan. |
| Finance / Contracts Lead | Pays participant stipends and reimbursements on time (SOP-310). |
| Regulatory Coordinator | Submits retention materials (for example newsletters, cards, reminder texts) to the IRB for approval before use. |
4. Definitions
| Term | Definition |
|---|---|
| Discontinuation of IP | The participant stops taking the investigational product but remains in the study for follow-up visits or contact as the protocol describes. |
| Withdrawal of Consent | The participant tells the site they no longer wish to take part. The participant may withdraw from all study activities or from some, for example from IP but not from follow-up. |
| Investigator-Initiated Withdrawal | The investigator removes a participant from IP or from the study, for example for safety, noncompliance, pregnancy, or a protocol-defined stopping rule. |
| Lost to Follow-Up | Status given when a participant stops attending and cannot be reached after the documented contact attempts in this SOP and the protocol. |
| Visit Window | The protocol-defined range of days in which a visit must take place. |
| Vital Status | Whether a participant is alive or dead and, where applicable, the date of death. |
5. Procedure
5.1 Retention Plan
5.1.1
Before the first participant is enrolled, the Lead CRC prepares a retention plan for the study, approved by the PI and filed in the ISF. The plan states:
- visit schedule and windows, and how visits will be scheduled and reminded
- contact methods participants may choose (phone, text, email, mail) and how consent to each is recorded
- retention materials and whether IRB approval is needed for them
- transport, parking and reimbursement arrangements (SOP-310)
- remote or home visit options the protocol allows (SOP-313)
- expected retention risks for the population and actions to address them
5.1.2
Retention materials that participants will see (for example appointment cards, newsletters, thank-you notes, text message templates with study content) are submitted to the IRB and used only after approval, unless the IRB's policy exempts them. Retention gifts and payments follow SOP-310 and the IRB-approved consent.
5.2 Contact Information and Contact Log
5.2.1
At enrollment, the CRC records the participant's contact details, preferred contact methods and times, and at least one alternate contact where the participant agrees and the consent form allows. The CRC confirms the details at each visit.
5.2.2
The CRC records every retention contact and attempt (reminders, missed-visit calls, letters) on F-309-01 or in the participant's source, with date, method, staff initials and outcome.
5.2.3
Text and email messages do not contain diagnosis, study drug or other sensitive health information unless the participant has agreed in writing to that method and the IRB has approved the content (SOP-400).
5.3 Visit Windows and Reminders
5.3.1
The CRC schedules each next visit before the participant leaves, within the protocol window, and gives the participant the date in writing.
5.3.2
The CRC reminds the participant before each visit [DEFAULT: 1 to 3 days before the visit, by the participant's preferred method] and records the reminder.
5.3.3
If a participant misses a visit, the CRC contacts the participant [DEFAULT: by the next business day] to reschedule within the window. Visits that cannot be held within the window are recorded as deviations (SOP-308).
5.3.4
The Lead CRC reviews upcoming windows weekly so visits are not missed for scheduling reasons.
5.4 Distinguishing Discontinuation, Withdrawal and Investigator-Initiated Withdrawal
5.4.1
When a participant says they want to stop, the CRC or investigator asks, without pressure, whether they want to stop:
- taking the IP only, but continue study visits or contact
- study visits, but allow follow-up by phone or through medical records
- all further participation, including contact and data collection
5.4.2
The staff member records the participant's exact choice in source. The default is not complete withdrawal: unless the participant clearly withdraws from all activities, the site offers continued follow-up as the protocol describes.
5.4.3
Before the participant leaves the study, the investigator explains any safety follow-up the protocol recommends (for example an end-of-treatment visit, washout or tapering of IP, return of IP or devices) and the participant's options for medical care. The participant may decline these.
5.4.4
An investigator may discontinue IP or withdraw a participant for the reasons the protocol lists or to protect the participant. The investigator records the reason and the decision in source and informs the participant. Where possible, a participant who stops IP continues follow-up as the protocol describes.
5.5 Reasons for Withdrawal
5.5.1
A participant is not required to give a reason for withdrawing. The investigator or delegated staff member makes a reasonable effort to learn the reason, while fully respecting the participant's rights.
5.5.2
Staff may discuss the participant's concerns to see whether they can be addressed (for example visit timing, transport, side effects), and may explain the value of continued participation. Staff do not pressure, repeat the request after the participant has declined, or link continued payment or care to staying in the study.
5.5.3
If the participant gives no reason, the CRC records "participant declined to give a reason." Staff record the reason as given, without interpretation.
5.6 Data After Withdrawal
5.6.1
Data collected before withdrawal stay in the study database and are not removed. FDA's 2008 guidance, Data Retention When Subjects Withdraw from FDA-Regulated Clinical Trials, explains that its recordkeeping regulations require this for FDA-regulated studies. The consent form should state this. Staff do not offer participants removal of data already collected.
5.6.2
If the participant agrees to continued follow-up, the CRC records the agreement in source, stating what may be collected (for example phone contact, medical records, specimens already collected), and continues as the protocol describes. A new consent or addendum is used where the IRB or sponsor requires it.
5.6.3
If the participant withdraws from all follow-up, staff do not contact the participant for study purposes and do not access their medical records or other confidential records for the study after the withdrawal date. Staff may still review study data collected before withdrawal. If the participant revokes the HIPAA authorization, the revocation must be in writing; the site stops new uses and disclosures of the participant's PHI for the study but may continue to use PHI already obtained to the extent needed to protect the integrity of the research (45 CFR 164.508(b)(5)) (SOP-400).
5.6.4
After a participant withdraws from all follow-up, FDA's 2008 guidance permits the investigator to consult public records, such as those establishing survival status (for example death records). When the sponsor or protocol asks for vital status, the CRC may search public records unless the consent form, the IRB or the participant's documented withdrawal choices restrict it, and records each search, its date and its source in the participant file. Public records do not include the participant's medical records or other confidential records, which staff do not access after full withdrawal (section 5.6.3).
5.6.5
Stored samples: use, destruction or retention of samples already collected follows the consent form, the protocol and the participant's stated wishes. The CRC informs the sponsor of any request to destroy samples (SOP-311).
5.6.6
Safety information the site learns after withdrawal (for example a participant calls to report a serious event) is still assessed and reported as required (SOP-500, SOP-501).
5.7 Recording and Notifying
5.7.1
For each discontinuation or withdrawal, the CRC records in source the date, who initiated it, the scope of withdrawal, any reason given, the safety follow-up offered and accepted, and the IP and device returns.
5.7.2
The CRC completes the end-of-treatment or end-of-study pages in EDC, updates IRT (SOP-307), and recovers IP (SOP-304).
5.7.3
The CRC notifies the sponsor as the protocol requires and updates F-303-01.
5.7.4
Where the participant agrees, the CRC sends the participant written confirmation of their withdrawal choices and keeps a copy in the participant file.
5.7.5
Withdrawal that results from an AE, pregnancy or a deviation is also handled under SOP-500, SOP-503 or SOP-308.
5.8 Lost to Follow-Up
5.8.1
When a participant misses a visit and cannot be reached, the CRC makes the first contact attempt within [DEFAULT: 1 business day] of the missed visit and records each on F-309-01.
5.8.2
Before a participant is declared lost to follow-up, the CRC makes [DEFAULT: at least 3 documented contact attempts, using at least 2 different methods (for example phone, text, email, alternate contact), on different days and at different times, then a certified letter with return receipt to the last known address]. Where the protocol sets more attempts or a different method, the protocol applies.
5.8.3
Contact with alternate contacts is limited to what the participant authorized and does not disclose study details beyond what the consent allows.
5.8.4
Where the consent form allows, the CRC may check the participant's medical records at the site or affiliated practices for recent contact, hospitalization or death.
5.8.5
Public record and vital status searches follow section 5.6.4.
5.8.6
If there is no response by [DEFAULT: 30 days after the certified letter is sent], the PI reviews the attempts and confirms lost to follow-up status in source. The CRC records the date of last contact, updates EDC and F-303-01, and notifies the sponsor.
5.8.7
If a participant declared lost to follow-up later makes contact, the CRC informs the PI and the sponsor, and the participant may resume follow-up as the protocol allows.
5.9 Retention Monitoring
5.9.1
The Lead CRC reviews retention for each study [DEFAULT: at least monthly]: missed visits, out-of-window visits, discontinuations and withdrawals, and the reasons recorded.
5.9.2
The PI and Lead CRC adjust the retention plan where a pattern appears (for example many withdrawals after a particular visit). Changes to participant-facing materials go to the IRB first.
6. Related Forms and SOPs
- F-309-01 Participant Contact and Retention Log
- F-303-01 Screening and Enrollment Log
- F-304-01 Investigational Product Accountability Log
- F-310-01 Participant Payment Log
- F-905-01 Cross-Entity Data Flow Register (Model N only)
- SOP-300 Participant Recruitment, Pre-Screening and Advertising
- SOP-301 Informed Consent Process and Documentation
- SOP-304 Investigational Product Management
- SOP-307 Case Report Forms, EDC Entry and Query Resolution
- SOP-308 Protocol Deviations and Noncompliance
- SOP-310 Participant Payments and Reimbursement
- SOP-311 Biological Specimen Collection, Processing and Shipping
- SOP-313 Decentralized Trial Elements (Remote Visits, Home Health, Direct-to-Participant IP)
- SOP-400 Participant Privacy and HIPAA in Research
- SOP-500 Adverse Event Identification, Assessment and Recording
- SOP-501 Serious Adverse Event and Expedited Safety Reporting
- SOP-503 Pregnancy Reporting in Clinical Trials
- SOP-905 Network Data, Systems, Privacy and Records Across Sites (Model N only)
- Appendix B Central and Site Responsibility Matrix (Model N only)
7. References
| Reference | Title |
|---|---|
| 21 CFR 50.25(a)(8) | Elements of informed consent: voluntary participation and right to discontinue |
| 21 CFR 50.25(b)(4) | Additional elements: consequences of withdrawal and orderly termination |
| 45 CFR 46.116 | General requirements for informed consent (federally funded research only) |
| 45 CFR 164.508(b)(5) | HIPAA authorization: revocation |
| ICH E6(R3) Annex 1, 2.9 | End of Participation in a Clinical Trial |
| FDA Guidance (Oct 2008) | Data Retention When Subjects Withdraw from FDA-Regulated Clinical Trials |
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