Submitting a Monograph

Raw data should be limited to symptoms reported by the subjects, clarifying inputs from the investigating team that result from interactions with the subjects and any collected objective data on the subjects. To enhance transparency of the Proving, data sets should be labeled according to their source and source of entry.

Subjects shall record all mental, emotional, and physical symptoms in their own words in the diary format as prescribed before Proving initiation (hereafter referred to as Subject Diary or Subject Entry).

Supervisor and/or Principal Investigator (hereafter referred to as Supervisor or Investigator) inputs occur during or after the Proving period as a result of direct interrogation or examination of the subject, and should help ensure completeness of symptoms and clarify raw data to reduce errors in interpretation.

Principal Investigator will ensure that raw data entry will be linked and locked to the source of data:

a) Data entry category permission is linked to the appropriate level of input (i.e. subject entries only by subjects, supervisor entry only by supervisors, etc.).
b) Continuity of subject data must be guaranteed (i.e. all data entered for a given subject remains tied only to that subject).
c) All data entered by subjects and supervisors must remain intact as originally entered.

1. Modifications or clarifications must be entered as new data and marked as such.
2. Clarification of raw data entry by members of the investigation team should occur prior to final sealing of data.

d) Once diary information and supervisor inputs are complete, data should be marked as sealed and no further changes to sealed data can be permitted.

Principal Investigator will ensure adequate protection of all Protected Health Information ⁽¹⁾.

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

Subjects shall record all mental, emotional, and physical symptoms in their own words in the diary format as prescribed before Proving initiation. Emphasis should be placed upon the inclusion of all physical, emotional and mental sensations or symptoms that occur.

The time period during and shortly after IPS administration is considered a critical period for data collection.

a) Diary entry shall be at least daily while IPS is administered and for at least 2 weeks after last dose.

d) Final subject diary entry should occur at the final follow up of the Proving and should be labeled accordingly.

Supervisor / Principal Investigator Inputs are limited to information derived from any of the following sources:

a) Clarification of a symptom reported by the subject after questioning (subjective information to enhance the completeness or clarity of a symptom).
b) Direct examination (such as a physical finding like a rash, or other observations such as the behavior of the subject), if conducted
c) Biomarker testing (such as weight, blood pressure, laboratory analysis, etc.), if conducted

Prior to IPS administration, a case history shall be conducted on each subject.

This shall be conducted in a face-to-face encounter to include:

a) Age
b) Gender
c) Ethnicity
d) Past medical history including hospitalizations, surgical operations, and clinically important birth or genetic defects
e) Present medical history including current medications, other clinically important therapeutic interventions, medication allergies, and current medical conditions in active treatment
f) Prior mental, emotional or physical symptoms or ailments that resulted in treatment.
g) Clinically important symptoms experienced within the past 3 months including notation of strong modalities, peculiar symptoms, or characteristic symptoms.

After IPS administration, Proving data should be collected in accordance with the Proving protocol.

Supervisor shall review all subject diary entries as part of their periodic interview during the Proving period. Investigation and clarification of symptoms should be performed to increase precision of subject reported symptoms. Specific information should be solicited and recorded to include (when present):

a) Body location
b) Time of occurrence
c) Duration
d) Frequency of recurrence or periodicity
e) Severity (using a Likert or ordinal scale defined before Proving initiation)
f) Concomitance with other symptoms
g) Influence of any environmental, physiologic or behavioral factors (also called modalities) upon the symptoms that increase or decrease the severity.
h) Identifiable potential etiologic factors determined by either temporal or presumed causative relatedness to onset of a symptom.

Specific investigation of any symptoms that resemble past complaints, that have recurred or changed after the administration of the IPS, should be conducted to determine severity, duration and frequency relative to status prior to the test period.

Pre-defined symptom classification criteria for all subject reported symptoms is required.

In person evaluation by the Supervisor or Principal Investigator should be conducted at the final evaluation or exit point of the Proving for each subject.

Trial record storage will comply with all applicable regulations.