6  Change Log

6.1 Overview

This document provides an overview of changes made to the structure, content, and format of the Enroll HD Periodic Dataset (PDS) between each consecutive major (PDSX) and minor (RX) release, from the first (PDS1; R1) to the most recent (PDS6; R2). Information about files and file structure, variables (additions, exclusions, and modifications), coding systems, and quality control and identification risk protocol is provided. Sample size and visit counts by major and minor release are also documented. Individual participant value changes between major and minor releases are captured in separate documents, available on request.

6.2 Files and file structure

The files contained in each Enroll-HD PDS release are displayed in Table 6.1 .

Table 6.1: Files included in each PDS release.

PDS1 contained 9 files: baseline, comorbid, followup, general, nonpharmacotx, nutsuppl, pharmacotx, phonecontact, and subject. For PDS2, the prematureend file was added to the release.

The main changes in the PDS release file structure occurred between PDS2 and PDS3; seven new files were added (adhoc, assessment, enroll, event, participation, profile, registry), and six files were removed (baseline, followup, general, phonecontact, prematureend, subject).

PDS1 and PDS2 contained only data from the Enroll-HD study. PDS3, and all subsequent releases, also contain data from Registry 2, Registry 3 and Adhoc study data, where these data are available for EnrollHD participants. As a result, the registry and adhoc files were added for PDS3 and onwards. The registry file contains visit information collected as part of the Registry 2 and Registry 3 studies. All the visit information is included in a single file and includes information collected at baseline, each follow-up visit, and unscheduled visits. The adhoc file contains data collected about Enroll-HD participants prior to their participation in the Registry and Enroll HD studies. Both registry and adhoc files share the same structure as the enroll file, which was also introduced in PDS3 to capture the data previously included in the baseline, followup, and phonecontact files (see Figure 6.1 ). The enroll file also includes data from unscheduled visits that were not made available previously. The new assessment file summarizes all available assessments/forms for visits from each study; this file can be a very useful tool to determine which data are available from each study. The participation file (see Figure 6.1 ) contains all the variables from prematureend and some variables from the subject file (for example hdcat_l and subjstat). The profile file (see Figure 6.1) includes all the variables from the previously used general file and the additional variables presented in the subject file, namely region, caghigh and caglow.

Figure 6.1: Files undergoing structural changes only (same information retained) from PDS2 to PDS3. Orange boxes indicate PDS1 and PDS2 files; green boxes indicate files from PDS3 to the current PDS release.

Finally, the event file - an Enroll HD study specific file – was introduced for PDS3. This file was not available until PDS3 because the number of observed Enroll-HD reportable events prior to this release was relatively small, causing concerns about potential identification.

Four files remained the same in file name and structure since the beginning: comorbid, pharmacotx, nonpharmacotx, and nutsuppl. However, in the PDS3_R2 release, two files (pharmacotx and nutsuppl) were removed to limit the distribution of the MedDRA and WHO-DD coded data to researchers holding a MedDRA and/or WHO-DD license. For more details, please consult Variables and Coding sections.

No further modifications to file structure have been made since PDS3.

6.3 Variables

This section summarizes changes made to variables within each file between consecutive PDS releases, including new variables, variable exclusions, and variable modifications.

The number of variables included in each file of each PDS release is summarized in Table 6.2.

Table 6.2: Number of variables by file and PDS release.

Table 6.3 , Table 6.5, Table 6.7, Table 6.8 , and Table 6.9 provide information on sequential changes to variables (inclusions, exclusions, and modifications) between the final major versions of each PDS release.

For variables changes implemented between minor releases (PDS2_R1 to PDS2_R2, PDS3_R1 to PDS3_R2, and PDS6_R1 to PDS6_R2), a brief description of the reason why those changes were made and the variables impacted are available. Table 6.4 and Table 6.6 resume the changes between the different minor releases of PDS2 and PDS3, respectively.

The majority of variable changes were observed between PDS2 and PDS3 when data from additional studies were added, and additional data from the Enroll-HD study were made available in the PDS (e.g., events).

6.3.1 PDS1_R1 -> PDS2_R2

Table 6.3: Changes in the variables between PDS1 and PDS2.
File Variable Label Status
Baseline occupant UHDRS Total Functional Capacity - Occupation
Baseline finances UHDRS Total Functional Capacity - Finances
Baseline chores UHDRS Total Functional Capacity - Domestic chores
Baseline adl UHDRS Total Functional Capacity - ADL
Baseline carelevl UHDRS Total Functional Capacity - Care level
Comorbid seq Visit Index *
Followup seq Visit Index *
Followup occupant UHDRS Total Functional Capacity - Occupation
Followup finances UHDRS Total Functional Capacity - Finances
Followup chores UHDRS Total Functional Capacity - Domestic chores
Followup adl UHDRS Total Functional Capacity - ADL
Followup carelevl UHDRS Total Functional Capacity - Care level
Followup pbas1wo Group Depressed mood - Worst
Followup pbas2wo Group Suicidal ideation - Worst
Followup pbas3wo Group Anxiety - Worst
Followup pbas4wo Group Irritability - Worst
Followup pbas5wo Group Angry or aggressive behavior - Worst
Followup pbas6wo Group Lack of initiative (apathy) - Worst
Followup pbas7wo Group Perseverative thinking or behavior - Worst
Followup pbas8wo Group Obsessive-Compulsive Behaviours - Worst
Followup pbas9wo Group Delusions / paranoid thinking - Worst
Followup pbas10wo Group Hallucinations - Worst
Followup pbas11wo Group Disoriented Behaviour - Worst
Nonpharmacotx seq Visit Index *
Nutsuppl cmdostotI Total daily dose
Nutsuppl cmdosfrq Frequency
Nutsuppl seq Visit Index *
Nutsuppl cmdose__cmdostxt Dose / Unit (dose of one intake)
Nutsuppl cmfrq__1 Daily intake - in the morning
Nutsuppl cmfrq__2 Daily intake - at noon
Nutsuppl cmfrq__3 Daily intake - in the evening
Nutsuppl cmfrq__4 Daily intake - at night
Pharmacotx cmtrt__ing Ingredient – Modified Term
Pharmacotx cmtrt__atc Ingredient – Code (coded by ATC)
Pharmacotx cmdostot Total daily dose
Pharmacotx cmdosfrq Frequency
Pharmacotx seq Visit Index *
Pharmacotx cmdose__cmdostx Dose
Pharmacotx cmfrq__1 Daily intake - in the morning
Pharmacotx cmfrq__2 Daily intake - at noon
Pharmacotx cmfrq__3 Daily intake - in the evening
Pharmacotx cmfrq__4 Daily intake - at night
Phonecontact seq Visit Index *
Phonecontact dsterm Specify primary reason for participant's premature discontinuation from study (lost to follow up hint: failure of participant to return to follow-up visit and failure.
Prematureend subjid HDID (recoded) *
Prematureend studyid Study ID *
Prematureend visit Visit name *
Prematureend visdy Visit day *
Prematureend visstat Visit status *
Prematureend dsterm Specify primary reason for participant's Premature discontinuation from study (lost to follow up hint: failure of participant to return to follow-up visit and failure to be located by investigator)
Subject region Region (latest) *

Variable notes, including modification(s):

  • The option ‘Oceania’ was changed to ‘Australasia’ in the variable region.

Variable changes for PDS2 releases (R1, R2):

Regarding the releases (R1, R2) of the PDS2, just one variable change was made: the variable mhenr was renamed as mhenrfon the comorbid file. The variable coding remained unchanged, only the name was corrected and matches the name released on PDS1. The variables changes between releases are presented in Table 6.4 .

Table 6.4: Variables with changes between PDS2 minor releases

6.3.2 PDS2_R1 -> PDS3_R2

Table 6.5: Changes in the variables between PDS2 and PDS3.
File Variable Label Status
Adhoc age Age at visit *
Adhoc emplusl Could subject engage in gainful employment in his/her accustomed work?
Adhoc emplany Could subject engage in any kind of gainful employment?
Adhoc volunt Could subject engage in any kind of volunteer or nongainful work?
Adhoc fafinan Could subject manage his/her finances (monthly) without any help?
Adhoc grocery Could subject shop for groceries without help?
Adhoc cash Could subject handle money as a purchaser in a simple cash (shop) transaction?
Adhoc supchild Could subject supervise children without help?
Adhoc drive Could subject operate an automobile safely and independently?
Adhoc housework Could subject do his/her own housework without help?
Adhoc laundry Could subject do his/her own laundry (wash/dry) without help?
Adhoc prepmeal Could participant prepare his/her own meals without help?
Adhoc telephon Could subject use the telephone without help?
Adhoc ownmeds Could subject take his/her own medications without help?
Adhoc feedself Could subject feed himself/herself without help?
Adhoc dress Could subject dress himself/herself without help?
Adhoc bathe Could subject bathe himself/herself without help?
Adhoc pubtrans Could subject use public transport to get to places without help?
Adhoc walknbr Could subject walk to places in his/her neighbourhood without help?
Adhoc walkfall Could subject walk without falling?
Adhoc walkhelp Could subject walk without help?
Adhoc comb Could subject comb hair without help?
Adhoc trnchair Could subject transfer between chairs without help?
Adhoc bed Could subject get in and out of bed without help?
Adhoc toilet Could subject use toilet/commode without help?
Adhoc carehome Could subject's care still be provided at home?
Adhoc hvlt Hopkins Verbal Learning Test-R completed (optional)
Assessment subjid HDID (recoded) *
Assessment studyid Study ID *
Assessment visit Visit name *
Assessment seq Visit index *
Assessment visdy Visit day *
Assessment enrollment Enrollment
Assessment variable Variable
Assessment mhx Medical History
Assessment samples Samples
Assessment motor UHDRS Motor/Diagnostic Confidence
Assessment tfc UHDRS Total Functional Capacity
Assessment funct UHDRS Function Assessment/Independence Scale
Assessment cognitive Cognitive Assessments
Assessment mmse Mini Mental State Examination
Assessment physio Physiotherapy Outcome Measures
Assessment pbas Problem Behaviours Assessment - Short
Assessment csri Client Service Receipt Inventory
Assessment careqol Caregivers Quality of Life Questionnaire
Assessment sf12 Short Form Health Survey – 12v2
Assessment hadssis Hospital Anxiety and Depression Scale – Snaith Irritability Scale
Assessment cssrsfup Columbia-Suicide Severity Rating Scale - Annual
Assessment cssrsbl Columbia-Suicide Severity Rating Scale - Baseline
Assessment wpaishp WPAI-SHP
Assessment missedvisit Missed Visit
Assessment behaviour UHDRS Behavioral Assessment
Assessment summary Summary
Assessment gci Global Clinical Impression Scale
Assessment care Care Giver Questionnaire
Assessment pbahd Problem Behaviours Assessment for HD
Assessment sf36v2 SF-36v2 Health Survey
Assessment bdi Becks Depression Scale
Assessment hamilton Hamilton Rating Scale for Depression
Assessment sf36v1 SF-36v1 Health Survey
Comorbid studyid Study ID *
Enroll age Age at visit *
Enroll emplusl Could subject engage in gainful employment in his/her accustomed work?
Enroll emplany Could subject engage in any kind of gainful employment?
Enroll volunt Could subject engage in any kind of volunteer or nongainful work?
Enroll fafinan Could subject manage his/her finances (monthly) without any help?
Enroll grocery Could subject shop for groceries without help?
Enroll cash Could subject handle money as a purchaser in a simple cash (shop) transaction?
Enroll supchild Could subject supervise children without help?
Enroll drive Could subject operate an automobile safely and independently?
Enroll housework Could subject do his/her own housework without help?
Enroll laundry Could subject do his/her own laundry (wash/dry) without help?
Enroll prepmeal Could participant prepare his/her own meals without help?
Enroll telephon Could subject use the telephone without help?
Enroll ownmeds Could subject take his/her own medications without help?
Enroll feedself Could subject feed himself/herself without help?
Enroll dress Could subject dress himself/herself without help?
Enroll bathe Could subject bathe himself/herself without help?
Enroll pubtrans Could subject use public transport to get to places without help?
Enroll walknbr Could subject walk to places in his/her neighbourhood without help?
Enroll walkfall Could subject walk without falling?
Enroll walkhelp Could subject walk without help?
Enroll comb Could subject comb hair without help?
Enroll trnchair Could subject transfer between chairs without help?
Enroll bed Could subject get in and out of bed without help?
Enroll toilet Could subject use toilet/commode without help?
Enroll carehome Could subject's care still be provided at home?
Enroll sid1 Have you wished you were dead or wished you could go to sleep and not wake up?
Enroll sid2 Have you actually had any thoughts of killing yourself
Enroll sid3 Have you been thinking about how you might do this?
Enroll sid4 Have you had these thoughts and had some intention of acting on them?
Enroll sid5 Have you started to work out or worked out the details of how to kill yourself? Do you intend to carry out this plan?
Enroll int1 Group Intensity of Ideation – Most Severe – Type
Enroll int2 How many times have you had these thoughts?
Enroll int3 When you have the thoughts, how long do they last?
Enroll int4 Could/can you stop thinking about killing yourself or wanting to die if you want do?
Enroll int5 Are there things – anyone or anything (e.g. family, religion, pain of death) – that stopped you from wanting to die or acting on thoughts of committing suicide?
Enroll int6 What sort of reasons did you have for thinking about wanting to die or killing yourself?
Enroll sbh1 Group Suicidal Behavior - Actual attempt
Enroll sbh1n Total # of attempts
Enroll sbh2 Has subject engaged in Non-Suicidal Self-Injurious Behavior?
Enroll sbh3 Has there been a time when you started to do something to end your life but someone or something stopped you before you actually did anything?
Enroll sbh3n Total # of interrupted
Enroll sbh4 Has there been a time when you started to do something to try to end your life but you stopped yourself before you actually did anything?
Enroll sbh4n Total # of aborted
Enroll sbh5 Have you taken any steps towards making a suicide attempt or preparing to kill yourself (such as collecting pills, getting a gun, giving valuables away or writing a suicide note)?
Enroll sbh6 Suicidal behaviour was present during the assessment period?
Enroll sbh7 Completed Suicide was present during the assessment period
Enroll attmpt1dy Day of most recent attempt
Enroll attmpt11 Actual Lethality/Medical Damage
Enroll attmpt12 Potential Lethality
Enroll attmpt2dy Day of most lethal attempt
Enroll attmpt21 Actual Lethality/Medical Damage
Enroll attmpt22 Potential Lethality
Enroll attmpt3dy Day of Initial/First attempt
Enroll attmpt31 Actual Lethality/Medical Damage
Enroll attmpt32 Potential Lethality
Enroll rfstdy Enrollment day
Enroll fhx Family History
Enroll bsp Biosamples for use in research
Enroll nvl Participation in sub-studies
Enroll cntct Contact between visits
Enroll cntctst Contact regarding other research studies
Enroll cntctpmt Contact regarding post-mortem tissue collection
Enroll rtrspctv Linking clinical information from previous studies
Event subjid HDID (recoded) *
Event studyid Study ID *
Event seq Index *
Event evtdy Day of report
Event evtcode Reportable event codes
Event evtterm__modify Event term – Modified Term (coded with MedDRA)
Event evtterm__decod Event term – Code (coded with MedDRA)
Event evtstdy Onset day
Event stdtcest Date estimated
Event evtongo Resolved
Event evtendy End Day
Event evtdsmc Status of DSMC review
Nonpharmacotx studyid Study ID *
Nutsuppl subjid HDID (recoded) *
Nutsuppl studyid Study ID *
Nutsuppl cmcat Type
Nutsuppl cmdostot Total daily dose
Nutsuppl cmdosunit Unit
Nutsuppl cmdosfrq Frequency
Nutsuppl cmstdy Start Day
Nutsuppl cmenrf Ongoing
Nutsuppl cmendy End day
Participation study Study *
Participation subjstat Participant status (latest)
Participation hdcat_0 Participant category (at enrollment)
Participation hdcat_l Participant category (latest)
Participation age_0 Age at enrollment
Participation rfstdy Study reference start day (baseline)
Participation rficdy Day of informed consent
Participation rfendy Day of end of study
Participation evtnum Number of events
Participation saenum Number of serious events
Participation visitnum Number of visits
Participation visit1, …, visit21 Visit type
Participation vis1dy,…, vis21dy Day of visit
Participation seq Visit Index *
Participation visit Visit name *
Participation visdy Visit day *
Participation visstat Visit Status *
Pharmacotx subjid HDID (recoded) *
Pharmacotx studyid Study ID *
Pharmacotx cmtrt__modify Drug name – Modified Term (coded by WHO-DD)
Pharmacotx cmtrt__decod Drug name – Code (coded by WHO-DD)
Pharmacotx cmtrt__ing Drug name - Ingredients
Pharmacotx cmtrt__atc Drug name – ATC Codes
Pharmacotx cmindc__modify Indication – Modified Term (coded by MedDRA)
Pharmacotx cmindc__decod Indication – Code (coded by MedDRA)
Pharmacotx cmdostot Total daily dose
Pharmacotx cmdose__cmdosu Unit (unit of one dose)
Pharmacotx cmdosfrq Frequency
Pharmacotx cmroute Route
Pharmacotx cmstdy Start day
Pharmacotx cmenrf Ongoing
Pharmacotx cmendy End day
Profile studyid Study ID *
Profile visit Visit name *
Profile visdy Visit day *
Profile visstat Visit status *
Profile age Age at visit *
Profile hdtest Has an HD genetic test been done?
Profile lbdy Collection Day
Profile fhx Family History
Registry age Age at visit *
Registry emplusl Could subject engage in gainful employment in his/her accustomed work?
Registry emplany Could subject engage in any kind of gainful employment?
Registry volunt Could subject engage in any kind of volunteer or nongainful work?
Registry fafinan Could subject manage his/her finances (monthly) without any help?
Registry grocery Could subject shop for groceries without help?
Registry cash Could subject handle money as a purchaser in a simple cash (shop) transaction?
Registry supchild Could subject supervise children without help?
Registry drive Could subject operate an automobile safely and independently?
Registry housework Could subject do his/her own housework without help?
Registry laundry Could subject do his/her own laundry (wash/dry) without help?
Registry prepmeal Could participant prepare his/her own meals without help?
Registry telephon Could subject use the telephone without help?
Registry ownmeds Could subject take his/her own medications without help?
Registry feedself Could subject feed himself/herself without help?
Registry dress Could subject dress himself/herself without help?
Registry bathe Could subject bathe himself/herself without help?
Registry pubtrans Could subject use public transport to get to places without help?
Registry walknbr Could subject walk to places in his/her neighbourhood without help?
Registry walkfall Could subject walk without falling?
Registry walkhelp Could subject walk without help?
Registry comb Could subject comb hair without help?
Registry trnchair Could subject transfer between chairs without help?
Registry bed Could subject get in and out of bed without help?
Registry toilet Could subject use toilet/commode without help?
Registry carehome Could subject's care still be provided at home?
Registry hvlt Hopkins Verbal Learning Test-R
NA NA completed (optional)
Registry hvltd Used form
Registry hvltt11 Trial 1: correct
Registry hvltt21 Trial 2: correct
Registry hvltt31 Trial 3: correct
Registry hvlt1 Delayed recall correct
Registry hvlt2 Total repetitions (trials 1-3 & delayed)
Registry hvlt3 Total intrusions (trials 1-3 & delayed)
Registry hvlt4 Recognition: true positives
Registry hvlt5 Recognition: false positives
Registry mdrs Dementia Rating Scale-2 completed (optional)
Registry mdrs1 Attention
Registry mdrs2 Initiation / perseveration
Registry mdrs3 Construction
Registry mdrs4 Conceptualization
Registry mdrs5 Memory
Registry sfscore_v1 SF-36 score
Registry sfscore_v2 SF-36 v.2 score
Registry behscore Behavioral score
Registry biscore Behavioral score incomplete
Registry behaviour_depscore Group Sub-scores - Depression
Registry defscore Group Sub-scores - Drive/executive function
Registry behaviour_irascore Group Sub-scores - Irritability/aggression
Registry behaviour_psyscore Group Sub-scores - Psychosis
Registry deprfr Group Depressed mood - Frequency
Registry deprsv Group Depressed mood - Severity
Registry guiltfr Group Low self-esteem/guilt - Frequency
Registry guiltsv Group Low self-esteem/guilt - Severity
Registry anxifr Group Anxiety - Frequency
Registry anxisv Group Anxiety - Severity
Registry suicfr Group Suicidal thoughts - Frequency
Registry suicsv Group Suicidal thoughts - Severity
Registry aggrfr Group Disruptive or aggressive behavior - Frequency
Registry aggrsv Group Disruptive or aggressive behavior - Severity
Registry irritfr Group Irritable behavior - Frequency
Registry irritsv Group Irritable behavior - Severity
Registry obsessfr Group Perseverative/obsessional thinking - Frequency
Registry obsesssv Group Perseverative/obsessional thinking - Severity
Registry compulfr Group Compulsive behavior - Frequency
Registry compulsv Group Compulsive behavior - Severity
Registry delusfr Group Delusions - Frequency
Registry delussv Group Delusions - Severity
Registry hallucfr Group Hallucinations - Frequency
Registry hallucsv Group Hallucinations - Severity
Registry apathfr Group Apathy - Frequency
Registry apathsv Group Apathy - Severity
Registry confus Does the examiner believe the participant is confused?
Registry dement Does the examiner believe the participant is demented?
Registry deprexam Does the examiner believe the participant is depressed?
Registry deprrfr Does the participant require pharmacotherapy for depression?
Registry irritrfr Does the participant require pharmacotherapy for irritability?
Registry isobt Was the behavioral assessment information obtained from:
Registry bdiscore Becks Score
Registry hamscore Hamilton Score
Registry sid1 Have you wished you were dead or wished you could go to sleep and not wake up?
Registry sid2 Have you actually had any thoughts of killing yourself
Registry sid3 Have you been thinking about how you might do this?
Registry sid4 Have you had these thoughts and had some intention of acting on them?
Registry sid5 Have you started to work out or worked out the details of how to kill yourself? Do you intend to carry out this plan?
Registry int1 Group Intensity of Ideation – Most Severe – Type
Registry int2 How many times have you had these thoughts?
Registry int3 When you have the thoughts, how long do they last?
Registry int4 Could/can you stop thinking about killing yourself or wanting to die if you want do?
Registry int5 Are there things – anyone or anything (e.g. family, religion, pain of death) – that stopped you from wanting to die or acting on thoughts of committing suicide?
Registry int6 What sort of reasons did you have for thinking about wanting to die or killing yourself?
Registry sbh1 Group Suicidal Behavior - Actual attempt
Registry sbh1n Total # of attempts
Registry sbh2 Has subject engaged in Non-Suicidal Self-Injurious Behavior?
Registry sbh3 Has there been a time when you started to do something to end your life but someone or something stopped you before you actually did anything?
Registry sbh3n Total # of interrupted
Registry sbh4 Has there been a time when you started to do something to try to end your life but you stopped yourself before you actually did anything?
Registry sbh4n Total # of aborted
Registry sbh5 Have you taken any steps towards making a suicide attempt or preparing to kill yourself (such as collecting pills, getting a gun, giving valuables away or writing a suicide note)?
Registry sbh6 Suicidal behaviour was present during the assessment period?
Registry sbh7 Completed Suicide was present during the assessment period
Registry attmpt1dy Day of most recent attempt
Registry attmpt11 Actual Lethality/Medical Damage
Registry attmpt12 Potential Lethality
Registry attmpt2dy Day of most lethal attempt
Registry attmpt21 Actual Lethality/Medical Damage
Registry attmpt22 Potential Lethality
Registry attmpt3dy Day of Initial/First attempt
Registry attmpt31 Actual Lethality/Medical Damage
Registry attmpt32 Potential Lethality
Registry svrtyll Based upon my review of the information, I feel the severity of illness is

Variable notes, including modification(s):

  • All the variables of the assessment file were introduced in the PDS3 release, since this file was not available before;

  • All the variables of the event file were introduced in the PDS3 release, since this file was not released on PDS2;

  • The following assessments were introduced due to the inclusion of the Registry 2, Registry 3 and Retro-Visit: Short Form Health Survey – 36v2 (SF-36v2), Short Form Health Survey – 36v1 (SF-36v1), Beck – Depression Inventory (BDI), Behaviour, Hamilton, GCI, and C-SSRS (Baseline and Follow Up). Some of these assessments were also introduced into Enroll;

  • The remaining variables of the adhoc and registry files were previously available in one of the visit files (baseline, followup or phonecontact) and, for that reason, are not included in the table.

Variable changes for PDS3 minor releases (R1 and R2):

Regarding the minor releases (R1, R2) of PDS3, two files previously made available in PDS3_R1 were removed in PDS3_R2, nutsuppl and pharmacotx, to limit distribution to only researchers holding a license for MedDRA and/or WHO-DD. The variables included in the nutsuppl and pharmacotx files on the PDS3_R1 and removed on PDS3_R2 are listed on Table 6.6 .

Table 6.6: Variables removed between PDS3 minor releases.
File Variable Label
Nutsuppl subjid HDID (recoded)
Nutsuppl cmcat Type
Nutsuppl cmtrt__modify Drug name – Modified Term (coded by WHO-DD)
Nutsuppl cmtrt__decod Drug name – Code (coded by WHO-DD)
Nutsuppl cmtrt__atc Drug name – ATC Codes
Nutsuppl cmtrt__ing Drug name – Ingredients
Nutsuppl cmdostot Total daily dose
Nutsuppl cmdosunit Unit
Nutsuppl cmdosfrq Frequency
Nutsuppl cmstdy Start day
Nutsuppl cmenrf Ongoing
Nutsuppl cmendy End day
Pharmacotx subjid HDID (recoded)
Pharmacotx cmtrt__modify Drug name – Modified Term (coded by WHO-DD)
Pharmacotx cmtrt__decod Drug name – Code (coded by WHO-DD)
Pharmacotx cmtrt__ing Drug name – Ingredients
Pharmacotx cmtrt__atc Drug name – ATC Codes
Pharmacotx cmindc__modify Indication – Modified Term (coded by MedDRA)
Pharmacotx cmindc__decod Indication – Code (coded by MedDRA)
Pharmacotx cmdostot Total daily dose
Pharmacotx cmdose__cmdosu Unit (unit of one dose)
Pharmacotx cmdosfrq Frequency
Pharmacotx cmroute Route
Pharmacotx cmstdy Start day
Pharmacotx cmenrf Ongoing
Pharmacotx cmendy End day

6.3.3 PDS3_R2 -> PDS4_R2

Table 6.7: Changes in the variables between PDS3 and PDS4
File Variable Label Status
Assessment cognitivel Extended Neuropsychological Assessment
Assessment function UHDRS Function Assessment/Independence Scale
Comorbid mhterm__modify Condition – Modified Term (coded)
Comorbid mhterm__decod Condition – Code (coded)
Enroll hxtobcpd Cigarettes per day
Enroll hxtobyos Years of smoking
Enroll tobcpd Cigarettes per day
Enroll tobyos Years of smoking
Enroll sdmtnd Symbol Digit Modality Test - Reason
Enroll verfctnd Verbal Fluency Test – Reason
Enroll scntnd Stroop Colour Naming Test - Reason
Enroll swrtnd Stroop Word Reading Test - Reason
Nutsuppl subjid HDID (recoded) *
Nutsuppl cmcat Type
Nutsuppl cmtrt__modify NutSuppl Supplement – Modified Term
Nutsuppl cmtrt__decod NutSuppl Supplement – Code
Nutsuppl cmtrt__atc NutSuppl Supplement - ATC Code(s)
Nutsuppl cmtrt__ing NutSuppl Supplement - ingredient(s)
Nutsuppl cmdostot Total daily dose
Nutsuppl cmdosunit Unit
Nutsuppl cmdosfrq Frequency
Nutsuppl cmstdy Start day
Nutsuppl cmenrf Ongoing
Nutsuppl cmendy End day
Pharmacotx subjid HDID (recoded) *
Pharmacotx cmtrt__modify Drug name – Modified Term
Pharmacotx cmtrt__decod Drug name - Code
Pharmacotx cmtrt__ing Ingredient – Modified Term
Pharmacotx cmtrt__atc Ingredient – Code (coded by ATC)
Pharmacotx cmindc__modify Indication – Modified Term
Pharmacotx cmindc__decod Indication - Code
Pharmacotx cmdostot Total daily dose
Pharmacotx cmdose__cmdosu Unit (unit of one intake)
Pharmacotx cmdosfrq Frequency
Pharmacotx cmroute Route
Pharmacotx cmstdy Start day
Pharmacotx cmenrf Ongoing
Pharmacotx cmendy End day
Participation saenum Number of serious events
Pharmacotx cmtrt__modify Drug name – Modified Term
Pharmacotx cmtrt__decod Drug name – Code
Pharmacotx cmindc__modify Indication – Modified Term
Pharmacotx cmindc__decod Indication – Code
Profile sxs_m Group Mixed symptoms – motor
Profile sxs_c Group Mixed symptoms – cognitive
Profile sxs_p Group Mixed symptoms – psychiatric
Profile sxs_o Group Mixed symptoms – oculomotor
Profile sxf_m Group Mixed symptoms – motor
Profile sxf_c Group Mixed symptoms – cognitive
Profile sxf_p Group Mixed symptoms – psychiatric
Profile sxf_o Group Mixed symptoms – oculomotor
Profile sxreas Please specify why you, as a ratter, cannot estimate symptom onset (without additional external information) at the moment
Profile sxgs What is your best guess of how many years ago symptom onset took place
Profile sxgsdy Day of data entry
Profile sxr_m Group Mixed symptoms – motor
Profile sxr_c Group Mixed symptoms – cognitive
Profile sxr_p Group Mixed symptoms – psychiatric
Profile sxr_o Group Mixed symptoms – oculomotor
Profile xgwas Additional GWAS data
Profile xbsp Additional biosamples available
Profile xpheno Additional phenotypic data available
Profile xmorpho Additional morphometric data available
Profile ximage Raw images available

Variable notes and modification(s):

  • The variable funct (“UHDRS Function Assessment/Independence Scale“) of the assessment file had its name changed to function in PDS4 release;

  • Regarding the profile file, additional variables (xgwas, xbsp, xpheno, xmorpho, and ximage) were added to allow researchers to easily identify if additional data or biosamples were available for each participant. These additional data and biosamples are from studies other than Enroll-HD and Registry, like Predict-HD, Track, among others, and can be requested through a SPS;

  • Concerning the pharmacotx and nutsupp files that were reintroduced in the PDS4 release, all medications and nutritional supplements have been included using new Enroll-HD specific medication and comorbidity codes, which replace all MedDRA coding;

  • Regarding the comorbid file, all WHO coding used in previous versions of PDS releases have been replaced by Enroll-HD specific codes.

Variable changes for PDS4 releases (R1, R2, R3):

Between the minor releases (R1, R2, and R3) of PDS4,there were no changes in the variables (included, excluded or modified). However, some coding on the following files were updated between PDS4_R1 and PDS4_R2: comorbid, event, nutsuppl, participation, pharmacotx, and profile:

  • profile: correction of information to the variables xgwas, xmorpho, xpheno, ximage, and xbsp;

  • participation: correction of the variable rfendy;

  • comorbid: correction of mhterm__modify and mhterm__decod;

  • pharmacotx: correction of cmindc__decod;

  • nutsuppl: correction of cmtrt__modify and cmtrt__decod;

  • event: correction of evtterm__modify and evtterm__decod .

6.3.4 PDS4_R3 -> PDS5_R2

Table 6.8: Changes in the variables between PDS4 and PDS5.

Variable changes for PDS5 releases (R1, R2):

Between the minor releases (R1, R2) of the PDS5, there were no changes in the variables (included, excluded or modified).

6.3.5 PDS5_R2 -> PDS6_R1

Table 6.9: Changes in the variables between PDS4 and PDS5.
File Variable Label Status
Adhoc height Height (cm)
Adhoc weight Weight (kg)
Adhoc bmi BMI
Adhoc bmi_imp BMI imputed
Adhoc capscore CAP score
Enroll hdiss_stage_imp Imputed HD-ISS stage
Enroll hdiss_stage0_prob Probability of classification as HD-ISS Stage 0
Enroll hdiss_stage1_prob Probability of classification as HD-ISS Stage 1
Enroll hdiss_stage2_prob Probability of classification as HD-ISS Stage 2
Enroll hdiss_stage3_prob Probability of classification as HD-ISS Stage 3
Enroll capscore CAP score
Enroll maristat Marital status
Enroll height Height (cm)
Enroll weight Weight (kg)
Enroll bmi BMI
Enroll bmi_imp BMI imputed
Nonpharmacotx cmfrq Daily intake
Registry maristat Marital status
Registry height Height (cm)
Registry weight Weight (kg)
Registry bmi BMI
Registry bmi_imp BMI imputed
Registry capscore CAP score

Variable notes, including modification(s):

  • The variable bmi_imp (BMI imputed) replaces the previous variable bmi and it is calculated based on observed weight at visit and height as observed at Enroll-HD baseline for all visits where the participant is at least 18 years of age (value is not provided for visits at which participant is < 18 years of age);

  • The variable capscore (CAP score) was introduced – please refer to the document Understand and Interpret the data for further information. See also: (Warner et al., 2022)

  • Multiple variables were introduced concerning HD-ISS staging (hdiss_stage_imp, hdiss_stage0_prob, hdiss_stage1_prob, hdiss_stage2_prob, hdiss_stage3_prob) - please refer to the Understand and Interpret the data document for further information. See also: (Tabrizi et al., 2022)

  • Several variables were removed or transformed to minimize participant identification risk (i.e., height, weight, maristat).

Variable changes for PDS6 releases (R1, R2):

Between the minor releases (R1, R2) of the PDS6, there were no changes in the variables (included, excluded or modified). However, certain variable values on the pharmacotherapy file were set to missing in the R2 of PDS6, in case cmtrt__modify were coded as Investigational drugs to avoid identification. These variables were dose (cmdostot), route (cmroute), and frequency (cmdosfrq).

6.4 Number of participants

Enroll-HD is an active, longitudinal study. A participant eligible for inclusion for one PDS release may be ineligible in the next (e.g., participant data quarantined). Table 6.10 presents sample size by PDS release, while Table 6.11 and Table 6.12 summarize the changes in participants between the last version of each PDS and between each release, respectively, regarding the new participants included, participants excluded, and those preserved from the previous release.

Table 6.10: Number of participants in each PDS release.
Table 6.11: Changes in the participants between consecutive PDS releases (final versions).
Table 6.12: Changes in the participants between PDS minor releases.

6.5 Visits

There are several types of visits included in the PDS. All PDS releases include Enroll-HD baseline, follow-up, and phone contact visits. Since PDS3, Enroll-HD unscheduled visits are also in the PDS, alongside baseline and follow-up visits from Registry (R2 and R3), and retrospective visits from ad hoc studies.

Table 6.13 summarizes the number of visits included in each Periodic Dataset release by visit type. In summary, no changes occurred in visits included between the releases of the same PDS, except for the PDS4_R2 and PDS4_R3, where a baseline visit was removed due to consent withdrawal of one participant, and for the PDS6_R1 and PDS6_R2, where two visits were removed for two family control participants.

Table 6.13: Number of visits by type in each PDS release

6.6 Coding

6.6.1 Missing Values

There are two overarching categories of missing data in the dataset: system-defined missing data (indicated by blank variable ‘entries’), and user-defined missing data (indicated by specific codes, which indicate reason for missingness). These user-defined labels - ‘exceptional values’ - were introduced in PDS4_R1 and have since remained unchanged. Each one of them is represented in the dataset by a specific code, detailed in Table 6.14 . For more details regarding the missing code values, please consult the Data Dictionary document.

Table 6.14: Resume of the missing values codes in use since PDS4.

6.6.2 Medications and Nutritional Supplements

For the PDS, the Enroll-HD participants’ use of medications and nutritional supplements are provided in two files: pharmacotx and nutsuppl, respectively.

The pharmacotx file includes coded data from the Enroll-HD database. PDS1 to PDS3 included information from the WHO-DD (WHO Drug Dictionary), which is used to code medications. For PDS4 and later versions, the WHO-DD information is replaced with Enroll-HD specific internal codes for medications in the variable cmtrt__decod (“Drug Name – Code”). The internal codes starts with RX, followed by 9 digits. End users with a license for the WHO-Drug Global may request access to the actual WHO-Drug Global codes. Before the release of PDS6, in the EDC the previous version of the WHO-DD (version 2012) had been updated to the WHO-Drug Global (version 2021). Therefore,some of the terms and codes (cmtrt__modify, cmtrt__decod, cmtrt__ing, cmtrt__atc) included in the PDS6 are different from the ones used in previous versions.

The indication for a medication is coded with MedDRA (https://www.meddra.org). From PDS4 on, the indication is coded with the internal Enroll‐HD condition code. The internal condition code starts with CX followed by 9 digits. End users with a license for MedDRA may request access to the actual MedDRA codes. Before the release of PDS6 in the Electronic Data Capture (EDC), previous PDS releases used MedDRA (2012 and 2015) versions. Therefore, some of the terms and internal codes values differ between PDS6 and previous versions. For additional details regarding the coding system, please consult the Coding Systems document available on the Enroll-HD General Study Document section on https://enroll-hd.org/.

6.6.3 Comorbidities

For participants in the Enroll-HD Study with documented comorbid conditions, the data are contained in the comorbid file of the PDS.

The comorbidities are coded with the ICD-10 code (https://icd.who.int/browse10/2010/en), the variables mhterm__modify (“Condition – Modified Term (coded)”) and mhterm__decod (“Condition – Code (coded)”) allow the user to check groups of diseases based on an organ system. Surgeries and procedures are coded using MedDRA. Since PDS4, the Enroll-HD internal condition code is included in the variable mhterm__decod. In PDS6 an updated version of MedDRA (2021) was used. Previous PDS releases used version of MedDRA (2015). Therefore, some of the terms and internal codes values differ between PDS6 and previous versions.

End users with a license for MedDRA may request access to the actual MedDRA codes.

For additional details regarding the coding system, please consult the Coding Systems document, available on the Enroll-HD General Study Document section on https://enroll-hd.org/.

6.7 Identification risk

To ensure that data included in each PDS release are HIPAA-compliant and that the risk for participant identification is minimized, two methods are employed: 1) “Safe Harbor” method; and 2) “Expert Determination” method. For full details of these methods, please refer to document Data Quality Management and Participant Privacy.

Expert Determination recommendations may include the transformation, aggregation, or suppression of certain variables flagged as potentially identifying.

Variables subject to aggregation, and their accompanying thresholds in each PDS release, are described in Table 6.15 to Table 6.17 .

Pursuant to variable transformation, aggregation, and suppression, data retained in the PDS releases is assessed for individual participant identification risk using the R software package sdcMicro (Templ, Kowarik, & Meindl, 2015). Genotype unknown participants exceeding a 1% identification risk probability are to be excluded from the dataset, for all other participants a 3% identification risk threshold is applied. The identification risk thresholds have remained unchanged across PDS releases. The variables considered in the analysis of identification risk have been updated, as described below:

PDS1 to PDS5 (including all minor releases):

  • age (baseline), caghigh, sex, race (aggregated), ISCED (baseline), BMI (baseline).

PDS6:

  • age (baseline), caghigh, sex, race (aggregated), ISCED (baseline), BMI (baseline), region

6.8 Aggregation thresholds

To minimize participant identification risk, data aggregation techniques are applied to specific variables for PDS releases. These variables, and the thresholds used for aggregation for each PDS release, might be different: the cohort size and profile allow for such aggregation threshold adjustments while maintaining low identification risk.

Determining a cut-off point to aggregate data is a trade-off between the amount of aggregation and the utility of the data: higher levels of aggregation are associated with lower precision of data.

Table 6.15 to Table 6.17 detail the variables aggregated in each PDS and their respective thresholds. All changes are highlighted in yellow. No changes have been made to variable aggregation thresholds since PDS2.

Note

Deaggregated data may be obtained through special request, subject to Scientific Review Committee (SRC) approval. Please refer to the Access Data and Biosamples webpage on www.enrollhd.org for information on how to request a specified dataset (SPS). The Understand and Interpret the data document provides additional detail on handling aggregated values.

Table 6.15: Aggregated variables and aggregation thresholds in PDS1.
Table 6.16: Aggregated variables and aggregation thresholds in PDS2.
Table 6.17: Aggregated variables and aggregation thresholds since PDS3 and subsequent releases.

6.9 Quality Control Procedure

Each Enroll-HD PDS goes through stringent Quality Control (QC) procedures prior to release. For full details of these methods, please refer to document Data Quality Management and Participant Privacy .

Up to and including PDS5, approximately 200 QC checks were applied to the data. For PDS6, check thresholds were reviewed and updated, and new checks added, for a total of approximately 400. New checks encompassed checks for new variables (e.g., capscore; HD-ISS variables) and systematic outlier checks for all continuous variables.

More detailed information on each check can be found in the document Quality Control: Observations and Unusual Findings. Document available on request. Please contact us.

6.10 Participant level values

Changes to individual participant data values between PDS releases, both major and minor, are not described in this document; they are captured and listed in individual spreadsheets, available upon request. These spreadsheets detail individual datum changes and the underlying reasoning for change (e.g., medication codes were changed).

6.11 Revision History

Document Name Summary of Changes
Change Log Overview: PDS1 to PDS6v20230104 First version for sixth Enroll-HD periodic dataset (PDS6; R1)
Change Log Overview: PDS1 to PDS6 v20230915 Second version for sixth Enroll-HD periodic dataset(PDS6; R2)
Tabrizi, S. J., Schobel, S., Gantman, E. C., Mansbach, A., Borowsky, B., Konstantinova, P., … Sampaio, C. (2022). A biological classification of Huntington’s disease: the Integrated Staging System. The Lancet Neurology, 21(7), 632–644. https://doi.org/10.1016/s1474-4422(22)00120-x
Templ, M., Kowarik, A., & Meindl, B. (2015). Statistical disclosure control for micro-data using the r package sdcMicro. 67. https://doi.org/10.18637/jss.v067.i04
Warner, J. H., Long, J. D., Mills, J. A., Langbehn, D. R., Ware, J., Mohan, A., & Sampaio, C. (2022). Standardizing the CAP score in huntington’s disease by predicting age-at-onset. Journal of Huntington’s Disease, 11(2), 153–171. https://doi.org/10.3233/jhd-210475