HCV CHIM Community Advisory Committee

The Advisory Committee met via Zoom from 12:00–1:00pm Eastern time on Monday, May 27, 2024.

Six of eight members attended. In alphabetical order: Julia Bacon, Jake Eberts, Carrielynn Lund, Thomas Smiley, Jennifer van Gennip, and Pam Young.

Comments below are presented with pseudonyms to encourage frank discussion, per the Committee’s guidelines.

Travel restrictions

From the protocol draft:

If the participant is required to travel for longer than 14 days or if there are any concerns about the safety of travel, the PI may recommend early treatment initiation. 

Participants who meet all eligibility criteria after screening will meet with the study coordinator to review the timelines for infection, plasmapheresis and treatment. Based on the participant availability, including no scheduled travel that will be of more than 14-day duration or interfere with study procedures, the date for the infection will be scheduled. The participant will be provided with a study card with emergency contact information for study personnel.  

Members reviewed proposed travel restrictions in the draft protocol and discussed their feedback. The committee concluded that the 14-day travel prohibition was not unreasonable. One member noted that travel generally heightens potential for exposure to disease, especially COVID-19, and flagged that this could be an issue for the study to consider, especially if there is a chance it confounds other data; information encouraging self-protection, e.g. through masking, may be advisable.

• Orange: A 14-day window seems reasonable. I originally interpreted this section wrong — But if someone says they’ll be gone for several weeks they disqualified? 
• Blue: Yes. You wouldn’t be admitted in the first place since they’ll talk about expected schedules. It seemed like regulators might have been potentially concerned about people going to places without strong health infrastructure when asking about this.
• Green: It’s nice for Health Canada to raise these concerns about travel, but in the world that we live in, getting sick when traveling is common. How would someone getting sick potentially confound other aspects of the study? To that end, should participants be required to mask? Ultimately, if you’re signing up for this you want to fully understand the expectations and you can agree or not agree – so if part of the agreement is to refrain from traveling for >14 days, that seems fine — they could be even more restrictive if the study wanted to. For an Indigenous person, timing might depend on time of year (e.g., powwow trails in the summer might interfere). So it’s important people know of the scheduling up front.
• Blue: The sickness while traveling point is a good one. As a non-doctor, my guess is the study’s thinking is that because they are selecting for generally healthy people and because hep C is a liver disease, the risk of severe COVID confounding the study is pretty low. If you ask people to strictly mask for all nine months or so of a study, you might lose a lot of prospective participants, so there’s definitely a balance.
• Green: Overall, 14 days sounds okay, perhaps adding language re: self protection with masking, etc. would be advisable. 
• Orange: Agree with the 14 days limit. Re: health protection, it’s ultimately imperative that people understand what they’re signing up for; language encouraging protection is fine, but it will be the choice of participants.
• No others had objections to the 14 day timeline. 

Sexual partner information

Prior to inoculation with the CHIM inoculum, participants will undergo counseling by a qualified member of the study team. Counseling will include re-review of the study procedures and provision of additional written material about HCV infection, with a focus on mitigation of risk of transmission. Copies of written material will be provided to share with intimate partners or household contacts of the participant.  

The study team asked for input into how sexual partners of participants might be informed. Jake explained that the study team was trying to strike a balance between full informed consent for partners and not providing any information whatsoever. Draft text for a pamphlet for sexual partners was also shared. There was general support for the pamphlet-based approach.

• Yellow: This might be a point to get input from HIV Legal Network, because of an HIV/HCV criminalization issue — people passing it on knowingly might face legal risk in Ontario or elsewhere.
• Blue: A pamphlet for use by participants to share with seems reasonable, ultimately it will be based on a trust relationship with participants.
• Yellow: I agree that a pamphlet is good, and it might be important to tell participants that not sharing that info could have legal repercussions for them. Definitely relevant for HIV. 
• Orange: [My jurisdiction] apparently has a similar law specific for knowingly spreading HIV.
• Purple: The pamphlet approach is reasonable. I think as long as people are informed of risks, even if low, and potential legal obligations, that should be good.
• Green: Yellow’s point of making sure people are aware of ramifications legally is very good. From another angle, what about tuberculosis, herpes, etc.? Are studies morally responsible for those as well if someone had it and spread them? For the sake of this study, we can mention HIV/HCV in legal terms, but a study is perhaps not morally responsible for an individual’s further transmission, but the legal responsibilities should be clear to them. It’s their decision whether they want to be responsible. The pamphlet draft looks good, especially if we add legal language as needed.
• Orange: The onus is on the participant ultimately to share the information responsibly.
• No other objections were raised. 

Alcohol and drug use

Alcohol use: Participants will be advised that alcohol use is not prohibited during the study period but avoidance of alcohol during the period of infection and treatment is recommended to avoid the theoretical risk of worsening liver injury. Participants will be counseled that if they opt to consume alcohol, it should be limited to no more than 7 standard drinks (12 grams of alcohol) per week or 4 standard drinks in 24 hours. They will be asked to record all alcohol use in their study diary and will be asked about alcohol use at study visits.  …

Drug and alcohol use – Drug and alcohol use pose concern for participation in this trial. Drug use that may lead to transmission of HCV is of particular concern and therefore any past or current injection or high-risk non-injection (ie. intranasal) drug use is an exclusion. The presence of a current or past substance use disorder, even if not related to substance use associated with HCV transmission (e.g. cannabis or alcohol use), may affect study adherence and therefore is an exclusion. Alcohol use disorder is associated with an increased risk of liver disease that could be worsened by transient HCV infection. Furthermore, an alcohol use disorder may affect adherence with study protocols. Therefore, any current or past alcohol use disorder will be an exclusion, with use of the well validated AUDIT-C as a screening tool.  Recreational alcohol use below the thresholds in AUDIT-C and recreational cannabis will not be excluded. Both alcohol and cannabis are legal and when used in modest amounts are not associated with liver disease or poor study adherence. Although study participants will be informed that it would be advisable to avoid alcohol for the duration of infection to reduce the theoretical risk of more severe liver disease during the HCV infection, modest alcohol use will not be an exclusion.  Participants will be advised to limit alcohol intake to <7 standard drinks per week and to avoid binge drinking (>4 drinks in a session), in line with the risk of liver disease (not overall health) in the low-risk Canadian alcohol guidelines. Alcohol intake will be documented by self-report in the study diaries and recorded at all clinical visits. 

• Blue: AUDIT-C somewhat contradicts the protocol itself as written, because someone drinking an average of one day a week would exceed the AUDIT-C score. I think the alcohol restrictions in the protocol text is fine, but I’d want to have it clarified whether a certain AUDIT-C score would be exclusionary. The marijuana guidelines are fine, too, especially since it doesn’t seem to implicate liver health in the same way as alcohol.
• Orange: These seem fine. The AUDIT-C probably should be a metric to flag for further scrutiny/discussion with prospective participants, but doesn’t need to be an exclusion criteria per se, perhaps. 
• Blue: Notably, they’re also doing checks of liver health already, so if someone has had problematic drinking habits for some time, it would likely be apparent in those other tests and the study would want to exclude them anyways. So the concern here is maybe for someone who more recently began problematic drinking. 
• Green: Will alcohol consumption be self-reported, and if so, will constraints on consumption just encourage people to lie? Unless it comes up on the liver panel – how definitive is that? Alcohol is damaging to the liver, but we should make sure participants know the risk thresholds. 
• Blue: Yes, I believe it would be self-reported.
• Green: I have some concerns from a socioeconomic angle – if you have a drinking problem you might not self-disclose that if there’s something like $20,000 involved. But if the drinking hasn’t affected your liver badly enough to show up, then as far as I am concerned that is not enough to warrant shutting it down for someone. As part of these studies, if people start problem drinking, we ask people to engage in certain behavior modification and hope that people can interact with study for support measures. But it’s not our way or the highway unless that impacts the validity of the study itself. 
• Yellow: It’s about the informed consent process. You need to understand that even if you don’t feel it yourself, it’s in your best interest as a participant to not drink excessively. The proposed wording doesn’t come off as punitive/overly monitoring to me, which is good. Odds of issues here are low – people will already be screened out with IDU and long-term alcohol consumption problems.  

Loss to followup

Avoidance of loss to follow-up: Participants will be reminded of the importance of follow-up, particularly through to documentation of cure (SVR12). Participants will be asked to provide information for an emergency contact who the study team may contact in the event that the participant cannot be contacted or located directly. Participants will also be asked as an optional consent to consent to linkage to administrative health data. Linkage to administrative health data would allow the study team to monitor the health of the participant through their interactions with the Ontario health care system if the participant was lost to follow-up. This access would also allow the study team to determine if the participant received HCV treatment in the unlikely event that a participant was lost to follow up and never received treatment through the study. 

The committee was asked to consider whether proposed methods to attempt to reach participants lost to followup (through emergency contact information and Ontario health data) are reasonable. The consensus was that they are.

• Red: If you’re signing up for this, you’re necessarily agreeing to some giving up of your privacy. So this seems fair. 
• No other members expressed objections to this approach to participant followup. 

Participant staggering in stages 1, 2

One member sought to discuss another set of potential changes related to timeline. The member shared images showing potential collapse of some stages of the protocol in order to speed up the timeline. The committee discussed whether this format is reasonable and acceptable given potential risks to participants and in light of the overall goals of the HCV CHIM, and concluded that it is.

• Red: Hep C is a well understood disease and with additional testing of the blood samples used to challenge people, it seems reasonable to use a shorter timeline. 
• Blue: I agree, and I think if anything it’s even more appropriate given the numerous other precautions in place and the much slower pace without a staggered approach. As long as these risks are explained clearly and participants undergo informed consent, I don’t think it’s a problem. 
• Orange: The staggered, simultaneous/parallel approaches are common in many scientific contexts and it seems quite reasonable here. Moreover, if problems are more likely to present themselves early on, waiting the whole time doesn’t seem necessary.

No other members expressed objections to the staggered approaches. 

Qualitative interview 

A parallel, interview-based substudy is planned for the HCV CHIM. The CAB was asked to weigh on on the timing and content of questions, but for lack of time, was unable to generate substantive discussion on these issues, which will be a focus of the next meeting.