Submitting a Monograph

All data entered into the treatment record by treating clinicians or subjects must remain intact as originally entered.

Clarification of raw data entry by members of the investigation team must occur prior to final sealing of data

2. Modifications or clarifications must be entered as new data and marked as such

If applicable, criteria for the exclusion of any raw data from the data collection process must be established prior to initiation of data collection.

Specific mention of any excluded data shall be included in the Monograph Report.

Selection of subjects for treatment with the IHMP must be justified according to known information about the IHMP (including information from prior clinical cases, published information, toxicology, or provings).

Prospective studies shall establish guidelines for subject selection to receive treatment with the IHMP prior to study initiation.

Outcome measures shall be chosen to examine both specific and global health changes during the treatment period.

Outcome measures shall be chosen and reported in a manner to demonstrate the clinical utility of the IHMP.

Improvements in symptoms reported to be due to treatment with IHMP shall be evaluated using the HPCUS Case Outcome Assessment Tool (see Section 4.4.7), when applicable; or another widely accepted causality measure with justification.

Method and duration of storage of case records will comply with all applicable regulations and requirements of the Ethics Committee or IRB that approved the study.

PI ensures that link between the original case notes and patient record is maintained (if applicable).

Raw data for clinical cases may be collected from two primary sources:

a) Subject reporting

b) Examiner- / Investigator-gathered data including data from:

1. Questioning / interviewing

Observation

Biometric testing (if performed)

PI shall describe steps taken to ensure uniformity of case data collection.

Prior to IHMP administration, a case history and examination are conducted on each subject to include:

a) Age
b) Gender
c) Ethnicity
d) Past medical history including hospitalizations, surgical operations, major traumas (physical or psychological), other symptoms or ailments that resulted in treatment, and/or recurrent treatment
e) Clinically important birth or genetic defects
f) Current medical history including medical conditions in active treatment, medications, other clinically important therapeutic interventions, and allergies
g) Clinically important symptoms experienced within the prior three months including notation of strong modalities, peculiar symptoms, or characteristic symptoms
h) Identification of the chief complaint for the subject

IHMP attenuation, vehicle, route of administration, frequency of dosing, and duration of therapy shall be noted in the record for each subject.

Changes in IHMP attenuation, vehicle, route of administration, or frequency of dosing during the course of treatment shall be justified in the case report.

All follow-up visits (scheduled or unscheduled) shall be reported.

Outcome assessment on each follow-up must include:

a) Length of time from initiation of treatment with IHMP
b) Assessment of any interval change for the chief complaint
c) Assessment of any interval change in other clinically relevant symptoms or findings from initial visit
d) Any interval changes in other therapeutic interventions
e) Assessment of any interval change in global health status
f) New symptoms or findings since administration of IHMP
g) Recurrence of old symptoms or findings from the past not present at the time of initial visit (or 3 months prior to initial visit)
h) Any aggravated or worsening symptoms or findings present at the initial visit

Outcome assessment shall be conducted face-to-face with the original treating clinician (Deviation from this requirement must be documented and justified).

The Monograph Report shall provide access to original, de-identified data sets, if requested.

Data collection methods shall be designed and implemented with an aim to minimize bias.

Variables of interest shall be evaluated to determine relatedness to the IHMP and therefore the prevalence of such variables in the general population must be known or estimated.

Monograph sponsor shall provide access to original, de-identified data sets, if requested.

Monograph sponsor shall report what measures were taken to ensure integrity of code sets, allocation of verum and control treatments, and treatment to outcome evaluation matching.

Methods of data collection shall ensure that subjects remain blind to verum/control allocation.

Decision to un-blind an individual subject, in the case of an AE, shall be based upon therapeutic necessity.

SAEs may require un-blinding at the time of the event.

Un-blinding protocol must comply with the following requirements:

a) Maintains blinding during the experimental trial unless un-blinding is required
b) Limits the number of personnel, within the research team, who will have access to un-blinding information, only to those absolutely necessary
c) Controls which personnel have authority to access data
d) If individual blind is broken, the following must be recorded:

I. records any data access
II. including specific personnel who obtained or viewed this information
III. information that was obtained
IV. date that it was obtained
V. and reason for un-blinding

e) and includes guidance for when
un-blinding should occur

Trial protocols must contain adequate “fail-safe” procedures to assure immediate access to subject data during the clinical study.

A complete record of the discontinuance and reasons shall be part of the study record.

Data gathered prior to the occurrence of an AE which resulted in subject removal from the trial shall be included in the analysis.