Human Subject Involvement and Characteristics
Audio recordings and video recordings will all be of participants enrolled in an ongoing study of MDMA- assisted therapy in people with PTSD, with this study and all recording methods receiving approval from an IRB. Participants in this study are unpaid individuals, male or female, ages 18 through 70, who have been diagnosed with chronic posttraumatic stress disorder (PTSD) using DSM-IV criteria, with a score of 50 or above on the Clinician-Administered PTSD Scale (CAPS), a recognized measure of PTSD symptom levels. All participants must have failed to achieve remission of PTSD after at least three months of medication with a selective serotonin uptake inhibitor and at least six months involving at least twelve sessions of a recognized psychotherapeutic treatment. Aside from continuing to have significant PTSD symptoms after these treatments, all participants are physically healthy, as confirmed by detailed medical evaluation, and they cannot possess any contraindicating factors for the administration of MDMA. Because of the high co-morbidity of mood and anxiety disorders among people with PTSD (Faustman and White 1989), it is necessary to include individuals with these additional diagnoses (excluding bipolar affective disorder type I).
All participants must give written informed consent to having their study psychotherapy sessions video recorded in addition to consenting to take part in the study of MDMA-assisted psychotherapy in people with PTSD.
There are no additional inclusionary or exclusionary criteria for session videorecording.
Sources of Material
All participants' psychotherapy sessions, including experimental (MDMA or placebo-assisted) sessions are recorded to audio compact disk as part of the study protocol. As part of the proposed treatment manual and training development, video recordings will be made of all experimental and psychotherapy sessions in order to provide material for treatment manual development. Before using recordings in the context of this study, segments consisting of more than ten minutes of silence or inactivity will be removed from audio recordings, and segments containing identifying information will be removed from both audio and video recordings whenever possible. In addition, participants can stop the recording of part or all of a psychotherapy session at any point in time during the session, and they can request that portions of the recording be excised at a later date.
Aside from their role as a potential element in MDMA-assisted psychotherapy, audio recordings are intended for research purposes only. Video recordings are intended for research use only. Recordings are intended to provide the investigators with a means of observing and analyzing psychotherapy protocols and samples from these recordings may be used as examples in the treatment manual. When this is done, all identifying or potentially identifying information will be removed from these recordings to maintain confidentiality. In addition the video recordings may be useful to those participants who request copies to review their sessions visually as well as with the audio recordings.
Participants sign forms for the release of information to any of the individuals who will need to obtain this information. Participants will sign a separate document indicating written, informed consent for the videotaping of experimental and non-experimental psychotherapy sessions. Each recording will be identified only by the participant's initials on the source recording, and the participant's numeric identification on any copies of the recordings, as those supplied to the participant or to the psychotherapist. All audio and video recordings will be kept in a locked file drawer in a locked office. Other than the researchers involved in the treatment phase of the current MDMA/PTSD study and therefore, by necessity, know the participants' names, researchers with access to these recordings will not be provided with any information that would identify participants by name or by other means, such as social security number. Removing identifying information from recordings and restricting access to researchers directly involved in treatment manual development will prevent the dissemination of confidential data, with or without identifying information. Maintaining data in a secure environment will prevent the accidental or deliberate examination or removal of data. While it is possible that individuals may be identified on audio or video recordings through means other than their names, such as through physical appearance or vocal timbre, restricting access to recorded material greatly reduces the opportunity for identification. Copies of recordings will not contain any personally identifying information, and will be identified by subject number only.
Potential Risks
Recording psychotherapy sessions poses a risk to participant confidentiality, and the procedure of recording psychotherapy sessions may increase participant distress or discomfort during the psychotherapy session. While this possibility certainly cannot be ruled out, it is our impression thus far that the procedure of audio recording sessions does not cause significant distress or discomfort, and the participants have reported that they soon get used to it and are not bothered by it.
Recordings contain a wealth of information about participants beyond dialogue or reference to the participant's name. People can be potentially identified by voice in audio recordings, and by appearance in video recordings, with appearance including facial features, clothing, gait or movements, or other features of the participant. It is possible that viewers could identify a participant through listening to or watching session recordings if they have had some prior contact with a participant, as through acquaintance or friendship.
Audio recording of experimental (MDMA or placebo assisted) psychotherapy sessions is an element of the study of MDMA-assisted therapy in people with PTSD. Participants in the study receive copies of these audiotapes and are encouraged, but not required, to listen to experimental session recordings. Because consent for audio taping is part of the initial study informed consent, the only alternative to making audio recordings of experimental sessions is for the participant to elect not to take part in the ongoing study. The same will not be true for video recordings. Making video recordings of psychotherapy sessions is necessary for treatment manual development, but is not required of participants taking part in the ongoing study of MDMA-assisted psychotherapy. The alternative to video recording is to decline to consent to having video recordings made of the session; participants can still take part in the study of MDMA-assisted psychotherapy while declining to have their psychotherapy sessions videotaped.
Participants may find the videotaping of psychotherapy sessions to be distressing or uncomfortable, either because recordings might lead to a breach in confidentiality or because they are uncomfortable with how they may appear to themselves or others in the recording. For most, the discomfort or distress related to video recording will be far smaller than the discomfort associated with psychotherapy or MDMA, but some people may be especially distressed by the prospective of having their sessions recorded. It is also possible that awareness that their interactions with the investigators are being recorded may inhibit interactions between the participant and the investigators. Because audio recording is already included as part of the session protocol and because video recordings are required for producing a standardized treatment, the investigators must accept the potential alteration of interaction resulting from knowledge that a session will be recorded.
In writing the treatment manual, it is possible that the investigators may inadvertently provide enough information about a participant to render him or her identifiable. Such information might include details of the appearance, age or occupation of the participant, or details of traumatic event or events the participant experienced. Each individual descriptive element may not identify the participant when given alone, but if provided in biographical form, the information may contain enough details for others familiar with a participant to identify him or her.
Recruitment and Informed Consent
All recordings will come from participants enrolled in the study of MDMA-assisted psychotherapy in people with PTSD. Participants in this study are recruited through referrals made by physicians or psychotherapists, including referrals selected from among the patients of Dr. Mithoefer. Letters of referral specifically request the participation of crime victims experiencing PTSD symptoms, or people with a diagnosis of combat-related PTSD with a duration of no longer than five years. In addition, some participants are self referred, and in these cases permission is always obtained for the investigators to communicate with their psychiatrists and/or other therapists involved in their prior or ongoing treatment. Participants already enrolled in this study will be given additional consent materials relating to the videorecording of their psychotherapy sessions, and any prospective participants recruited after the investigators have begun to make videorecordings will receive two separate consent documents, one for participating in the study and one permitting recording of non-drug assisted and experimental psychotherapy sessions. Participants or prospective participants will discuss and review study procedures (including risks, potential benefits, and alternatives) before giving written informed consent. The investigators will clearly differentiate participation in the study of MDMA-assisted therapy, including the open-label study continuation, and consent to the videorecording of psychotherapy sessions. We will accept no one who, because of illness, intelligence, language or cultural differences, appears unable to understand the nature and risks of the experiment, or who is unable to read and follow the informed consent or, if blind, is unable to listen to or follow the informed consent when it is read to him or her.
Protection of Human Subjects
The investigators will be attentive to any potentially identifying information contained on audio or video recordings, and they will remove any identifying information from these recordings if necessary, such as the full name of the participant or the full names of other family members or their exact street addresses. As described below, the investigators will make every effort to strictly safeguard the confidentiality of all participants. The investigators will also stop making a video recording at the request of the participant at any point in time during the psychotherapy session.
Original audio and video recordings for each participant will only be marked with the participant's initials and a numeric code for each participant, and all recordings will be stored in a locked file cabinet. Copies of recordings will only be marked with the numeric code randomly assigned to each participant. This will be true both of copies given to participants and copies given to the investigator examining and analyzing recordings during treatment manual development.
Potential distress related to the recording of study psychotherapy sessions will be dealt with through discussing the recordings with the participants. Participants and investigators will discuss the nature and purpose of the videorecordings prior to the onset of session recording. Understanding the purpose of making video recordings of sessions, reminding participants of the degree of control they have over what is recorded, and reassuring them that they are not required to watch themselves on video is likely to reduce or eliminate distress or discomfort in most participants.
When writing the treatment manual, the investigators will refer to individual participants as "Participant," by participant number (such as "Participant 2"), or by a pseudonym. The investigators will discuss any extensive use of biographical material with a participant before using it in the treatment manual. If a particular set of demographic and trauma-related details are perceived by the participant or the investigators as providing enough information for identifying a specific participant, then the investigators may confer with the participant about ways to reduce risk of identification. Means of reducing participant identification in the treatment manual include omitting key pieces of information about the participant or providing readers with false information about the participant's place of residence, occupation, or the nature of his or her traumatic event. The investigators will inform readers when they are using pseudonyms or when omitting or falsifying aspects of the participant's life in order to maintain participant confidentiality.
Confidentiality of Records
Every effort will be made to strictly safeguard the confidentiality of all participants. Despite this, privacy cannot be guaranteed. Recordings of each participant's psychotherapy sessions will be identified only by the participant's initials on the original recording and by a numeric code on all copies of these recordings. Audio and video recordings will be kept in a locked file drawer in a locked office. Access to recordings will be limited to regulatory agencies, researchers assessing the participant for changes in symptoms, and individuals analyzing data, and other therapists rating the investigators on their adherence to the manual. With the exception delineated above, researchers with access to recordings will not be provided with any information that would identify participants by name or by other means, such as social security number. If necessary, identifying information may be erased or otherwise removed from recorded material.
Participants will sign forms for the release of information to any of the individuals who will need to obtain this information.
Removing identifying information from recordings and restricting access to researchers directly involved in conducting the study or producing the treatment manual, unless a specific exception is agreed to in writing by the participant, should prevent the dissemination of confidential data, with or without identifying information. Maintaining data in a secure environment will prevent the accidental or deliberate examination or removal of data. While it is possible that individuals may be identified on audio or video recording through means other than their names, restricting access to these recordings greatly reduces the opportunity for identification of participants.
Potential Benefits of the Proposed Research To The Subjects And Others
Participants enrolled in the ongoing study are provided with copies of audio recordings of each experimental (MDMA or placebo-assisted) psychotherapy session, and the investigators encourage them to listen to these recordings as part of the therapeutic process. Video recordings of psychotherapy sessions will be available to participants upon request. It is possible that participants may benefit from viewing video recordings of their sessions, though this benefit is not an expected outcome of study participation. The participants do not receive any other material benefits from permitting the video recording of their sessions.
Producing a standardized manual for conducting MDMA-assisted psychotherapy will permit the training of therapists who will conduct Phase III studies in the US. These findings may demonstrate the efficacy of MDMA-assisted psychotherapy, and this would lead to the development of another treatment option for people with PTSD. Even if study findings are not as promising as preliminary data now appears, developing a treatment manual will provide investigators with a clear account of the psychotherapeutic procedures they performed. It is possible that retaining a record of therapy procedures from this study will allow the investigators to alter and improve treatment procedures in a manner that enhances treatment efficacy. Lastly, video recordings provide researchers with a wealth of information about observable behaviors that are not preserved in audio recordings, narrative accounts or psychometric measures, and these observations are not altered by biases possessed by the participant or the investigators, as might occur in retrospective accounts. The videorecordings used in these sessions will be the first extensive visual records of MDMA-assisted therapy. It is possible that these recordings will prove to be a resource for researchers interested in studying the nature and process of MDMA-assisted psychotherapy, and for researchers interested in the effects of MDMA on emotion and social interaction.
Importance Of The Knowledge To Be Gained
If MDMA-assisted therapy is found to be a promising treatment for reducing or alleviating the symptoms of PTSD, psychotherapists will want to learn more about how to conduct MDMA-assisted psychotherapy, and the multi-site studies needed to further examine and confirm the efficacy of MDMA-assisted psychotherapy will require the existence of standardized procedures for performing MDMA-assisted therapy. Currently, information on the practice of MDMA-assisted therapy consists of anecdotal reports written prior to the scheduling of MDMA in the US or Europe (e.g. Adamson 1985; Greer and Tolbert 1998; Stolaroff 2004; Widmer 1998), and the results from one uncontrolled study that was not specific to studying the therapy in people with PTSD (Greer and Tolbert 1986). The current ongoing study is the first controlled, systematic investigation of the safety and efficacy of MDMA-assisted psychotherapy in a specific population, and the treatment manual under development will be the first of its kind. Crafting a set of standardized instructions for conducting MDMA-assisted psychotherapy is vital to progress in researching the efficacy of this potential treatment for PTSD. Even if study results fail to support the efficacy of this treatment, the treatment manual could be used to understand those results and to relate them to previous narratives and case studies. Writing the treatment manual will provide the investigators with the opportunity to review and consider the nature and structure of MDMA-assisted psychotherapy. Understanding how MDMA-assisted therapy is conducted in this specific patient population is liable to make it easier for the investigators and other researchers to apply this therapy to other populations of people with PTSD, as those whose PTSD arose from vehicular accidents, natural disasters, or life-threatening illnesses. It is also possible that writing the treatment manual will lead the investigators to improve and refine the stages of MDMA-assisted therapy in response to observing recorded sessions or re-evaluating study findings in the context of assessing consistency, adherence and competence of therapy performance.
The recordings the investigators will use to develop the treatment manual will be the first extensive record of MDMA-assisted therapy in people with PTSD, and this information is not equivalent to Phase I trials or anecdotal accounts of MDMA-assisted psychotherapy. Raw observations could be used to test hypotheses about the nature or structure of MDMA-assisted therapy or about the effects of MDMA on one or more specific observable behaviors. The treatment manual could serve as an aid in developing other related treatment manuals, as for the population of people experiencing anxiety as a result of advanced stage cancer. Investigators with access to a treatment manual detailing standardized procedures will be better able to point to similarities and differences between the use of MDMA in one condition, such as PTSD, and its use in another, such as cancer-related anxiety. More generally, the information contained de-identified transcripts of recordings and in the treatment manual could inform disparate areas of psychology and neuroscience, including clinical psychology, psychopharmacology, and social psychology. Researchers interested in therapist-patient interactions during psychotherapy, in the effects of MDMA upon behavior or emotion, and on other drug-specific or setting-specific behaviors could use the raw observations, transcripts of the observations or the treatment manual to test hypotheses about these areas of investigation. Use of the treatment manual or transcripts of the recordings used in treatment manual development would prove valuable even if further research fails to support the efficacy of MDMA-assisted therapy in people with PTSD.
Inclusion of Women and Minorities
Both men and women are eligible for participation in the ongoing study, without preference given to either gender. It is possible that there will be more women participants because PTSD arising from crime victimization is higher in women than in men. Women participating in the study must not be pregnant or lactating, and they must be using an effective means of birth control during the course of the study to avoid inadvertent prenatal exposure to MDMA. All participants have their experimental (MDMA or placebo-assisted) sessions recorded to audio compact disk. The investigators will make video recordings of all consenting participants, whether male or female, without preference for either gender.
Members of all ethnic or racial categories are eligible to participate in the ongoing study, without preference given to any race or ethnic group. It is anticipated that the racial/ethnic composition will be close to that of the regional population. Since the ongoing study is in 20 participants, it seems likely that not all racial/ethnic groups designated by the NIH will be represented in the proposed study. As noted above, audio recordings are made of experimental therapy sessions for all participants. The investigators will make video recordings of all consenting participants, without preference for any particular racial or ethnic group. Because video recordings will occur in an even smaller sample of participants enrolled in this pilot study, it is unlikely that the racial or ethnic composition of participants consenting to the videorecording of their psychotherapy sessions will be representative of the regional or national population.
Targeted/Planned Enrollment Table
See "Targeted Enrollment form" on p. 42
Inclusion of Children
Individuals between the ages of 18 and 70 are eligible to participate in the ongoing study of MDMA-assisted psychotherapy that will provide material for developing the treatment manual. Individuals who are unable to give adequate informed consent will not be enrolled in this study, including all individuals considered to be minors by the state of South Carolina. To date, there is insufficient information concerning the effects of MDMA-assisted therapy in adults with PTSD, therefore the FDA will not allow the study to be open to children under the age of 18. As noted above, audio recordings will be made of the experimental sessions of all participants, and video recordings will be made of psychotherapy sessions for all participants who consent to the recording of their sessions. s. We will attempt to show no preference in relying on material from participants of any given age group included in the study.
Data and Safety Monitoring Plan
All recordings used for treatment manual development, and any extensive transcripts of the recordings, will be stored in a locked file drawer in a locked office at the offices of Michael C Mithoefer MD, and copies of recordings sent to the other investigator will be stored in a locked file cabinet at the offices of June May Ruse PsyD. Recordings of experimental sessions will be edited to remove any identifying information prior to use as material for working on the standardized treatment manual. Participants will be identified by number and initials only in case report forms, and by number only in any computerized data. Access to recordings used in manual development will be restricted to investigators evaluating the sessions, though participants may receive copies of their own sessions for their review. Identifying information will also be removed from these recordings.
Data Safety Monitoring Board
The ongoing study that will provide the investigators with observations and examples for the treatment manual is a small pilot study, and no multi-site studies are proposed in this application. However, the sponsor employs a data safety monitoring board (DSMB) to assess the study of MDMA-assisted psychotherapy in people with PTSD. The DSMB is composed of three individuals, at least one of whom is a psychiatrist and another a psychotherapist with expertise in PTSD. The DSMB has meetings scheduled periodically to assess the safety of participants in the study of MDMA-assisted therapy. They report their recommendations as to whether the study should be continued as is, modified, or halted to the sponsor, the IRB and the FDA. They will also meet to review serious adverse events. The DSMB may discuss audiotaping and videotaping of psychotherapy sessions, but their main concern is the safety of MDMA-assisted psychotherapy as performed in this study.