Two years ago Quintiles launched iGuard, a personalized medication monitoring service for patients that doubles as a clinical trial recruitment tool. The multinational CRO has reported (as reported by PharmaTimes) that the service has over 2 million enrollees (Quintiles claims this is more than Twitter got in its first two years...a strange claim that to me is meaningless...like comparing apples and oranges...but that's another story) and that iGuard is even helping to reshape the clinical trial enrollment landscape.
The method by which this is allegedly happening is that patients are emailed information about a clinical trial and they either opt-in or they don't. Simple enough, but the other way that this service seems to be assisting trial recruitment is through patient feedback on new advertising schemes, compliance promoting measures, and retention tools. Doesn't that sound weird that the largest CRO in the world is making a big deal out of this when involving potential trial participants in the clinical trial process seems obvious? It has long been a concern of mine when central recruiting services present advertising and retention items to sites that clearly aren't effective, yet they are required by the sponsor to be utilized (some recruiting services, in my opinion, use more smoke and mirrors than actual results when selling their product to sponsors...but again, that's another story).
This system put together by Quintiles is a better example of how trial recruitment and retention should be researched and developed. After all, the participants are the ones that we are trying to bring in, so why not ask them what would catch their eye or what would encourage them to remain in a trial? Unfortunately because iGuard is managed by Quintiles, the results of such research remains the property of CRO and will likely not be disclosed to anybody who asks about it. Research sites, though, can take this plan and come up with some ideas of their own to get potential participants involved in the recruitment process. Here's a few ideas off the top of my head:
-Send out a poll included in an email newsletter asking about what recruitment ideas work best
-Have participants fill out a survey asking: why they participate? why they remain in the study? what would make them more likely to complete a trial rather than drop out? less likely?
-Interview willing participants on their entire trial experience, from recruitment to completion
-Be visible in the community. No one can argue against the importance of branding in advertising, so get out there and make a name for yourself.
30 December 2009
26 December 2009
I got the right temperature
Over the past couple weeks, there have been 3 notable incidents involving publicly available (and administered) vaccine efficacy being compromised. In two separate events MedImmune and Sanofi Pasteur recalled hundreds of thousands of H1N1 vaccine because of lower than expected antigen levels while in Ohio, a clinic had to inform over 2000 people that the H1N1 vaccine they received could have been frozen, thus potentially destroying the effectiveness of the shot to protect against swine flu. While these occurences are likely unrelated, they still represent a serious issue in the vaccine supply chain. The manufacturers all work as quickly as they can to produce a quality product that will protect patients from influenza, but sometimes things go wrong and in this case they went wrong at the worst possible time.
The Ohio incident could happen in any clinic, but what is bothersome to me is that the vaccination site claims that the vaccine was received in good order and was stored properly, thus indicating that the vaccine was either not packaged properly (eg with too much coolant) or was stored improperly at the distribution center. The other problems with low antigen levels are a strictly a sponsor problem, but they still shouldn't happen, especially when the public expects a quality vaccine to be produced that is not only safe, but also does what it is supposed to do. How do clinical trials factor into this? Well, as anyone involved in trials knows, sites and sponsors spend a large amount of time ensuring that the investigational product is shipped, stored, and administered properly. This includes strict temperature monitoring requirements in storage and shipping with the potential for significant consequences from sponsors and regulatory agencies if these requirements are not met. Temperature excursions can even compromise a site's ability to conduct vaccine trials because of the fast paced enrollment requirements of many studies (the mantra for many vaccine studies is: you snooze, you lose.). Sponsors must also adhere to strict temperature monitoring requirements because the FDA would likely not look favorably upon any submitted data that did not contain sound storage/shipping documentation (don't forget that ICH GCP guidelines and FDA regulations require this). The same goes for efficacy testing of investigational products, but that does not affect the sites to the same degree as temperature monitoring.
My message here is twofold:
1) Just because sponsors have an approved product, does not mean that a product should be shipped/stored/evaluated with any less diligence than in a clinical trial. Yes, the FDA won't pull a product off the shelves because of a temperature deviation (maybe a big fine for some egregious error), but public safety is still on the line. Please note that I'm not saying this happened with the recent issues, but it is a possibility
2) Research sites should look at these events and learn from them. Take the time to review practices for receiving, storing, and dispensing investigational products so that all federal and sponsor guidelines are met. Temperature monitoring is a really big deal, and it should never be overlooked or undervalued as somehow less important aspect of clinical trial conduct
The Ohio incident could happen in any clinic, but what is bothersome to me is that the vaccination site claims that the vaccine was received in good order and was stored properly, thus indicating that the vaccine was either not packaged properly (eg with too much coolant) or was stored improperly at the distribution center. The other problems with low antigen levels are a strictly a sponsor problem, but they still shouldn't happen, especially when the public expects a quality vaccine to be produced that is not only safe, but also does what it is supposed to do. How do clinical trials factor into this? Well, as anyone involved in trials knows, sites and sponsors spend a large amount of time ensuring that the investigational product is shipped, stored, and administered properly. This includes strict temperature monitoring requirements in storage and shipping with the potential for significant consequences from sponsors and regulatory agencies if these requirements are not met. Temperature excursions can even compromise a site's ability to conduct vaccine trials because of the fast paced enrollment requirements of many studies (the mantra for many vaccine studies is: you snooze, you lose.). Sponsors must also adhere to strict temperature monitoring requirements because the FDA would likely not look favorably upon any submitted data that did not contain sound storage/shipping documentation (don't forget that ICH GCP guidelines and FDA regulations require this). The same goes for efficacy testing of investigational products, but that does not affect the sites to the same degree as temperature monitoring.
My message here is twofold:
1) Just because sponsors have an approved product, does not mean that a product should be shipped/stored/evaluated with any less diligence than in a clinical trial. Yes, the FDA won't pull a product off the shelves because of a temperature deviation (maybe a big fine for some egregious error), but public safety is still on the line. Please note that I'm not saying this happened with the recent issues, but it is a possibility
2) Research sites should look at these events and learn from them. Take the time to review practices for receiving, storing, and dispensing investigational products so that all federal and sponsor guidelines are met. Temperature monitoring is a really big deal, and it should never be overlooked or undervalued as somehow less important aspect of clinical trial conduct
12 December 2009
The CROs can get it too
Sometimes it seems that whatever research sites do, there is always the threat of regulatory agencies coming down hard on investigators. Don't do this a certain way or the FDA will get you. Make sure you document this like so, or else an auditor will cite you. After hearing this repeatedly a research site must wonder if the bullseye is always squarely on the investigator. If you think I have good news about that, you're right..sort of. First of all, the responsibility to properly conduct a research trial does lie first and foremost with the investigator, but the FDA also has its eyes on the sponsor and those who contract with the sponsor to conduct the research.
This fact was brought to light last week when the FDA issued a potent warning letter to ICON, citing their inability to properly monitor a research study. Granted, the findings were likely issued to the corresponding investigators, but the number of citations was a reflection of the lack of a sound monitoring plan. This warning letter was surprising to me because the types of errors noted are not nitpicky, rather they are surprising violations of a variety of FDA regulations and GCP. I was shocked at the different findings noted by the FDA and even more surprised that the errors were not picked up during routine monitoring during the trial. Obvious drug dosing inconsistencies, discrepancies between the source and CRF, lack of drug accountability; the list goes on and on, but the point I'm making here is that even though monitors will always remind investigators of the importance of following FDA regulations and GCP, the monitors are also held accountable for their work (or lack thereof, when applicable).
So, research sites, read the warning letter and realize the burden of clinical research isn't squarely on your shoulders. Remember too though, that patient safety is your responsibility and if you ever question the quality of monitoring efforts, you can discuss this with the study sponsor. Both parties have a vested interest in quality study monitoring, and the FDA will take no sides when reviewing study data.
07 December 2009
Thoughts?
It's common knowledge to those in the clinical research industry that when a new ICF is issued, subjects actively participating in a trial should be reconsented to inform them of changes to the study so that they can decide whether or not they would like to continue participating. Generally the guidance as to whether the subject should be reconsented or not comes from the IRB, although the sponsor will supercede that decision (even though they shouldn't, in my opinion, but that's another story). This reconsenting process should mirror the initial consent discussion done prior to study entry, and 90% of the time subjects agree to continue their study participation...but what happens if the subject actually refuses to continue and won't sign the new consent?
When considering this, it seems there are three options:
1) Document the situation and let the patient leave without any early termination assessments because the subject is not a part of the new consent and hasn't agreed to any further study procedures
2) Document the situation, but proceed with early termination assessments if required by the protocol
3) Proceed with the new consent under the provision that the subject will sign consent, then immediately withdraw from the study.
After thinking about this for some time, I believe that option 2 is the best choice. Here's why: Some would argue that by declining to sign the revised ICF, the subject is withdrawing consent to participate in the trial, which is true. Also because there was a new ICF issued, the old consent is no longer valid and the subject is technically not participating under any ICF by the time they are presented with a new consent form. Thus any procedures done prior to the new consent would be done without the consent of the subject, and a big no-no. The previous two sentences are where my opinion differs.
By signing the original consent at the start of the study, the subject is agreeing to take part and follow all study procedures, including the early termination assessment. If a new consent is administered, the subject is still participating under the old consent and no further procedures may be carried out until the new consent is signed. However an early termination assessment is likely something that was required under the old protocol, and in almost every case, is a critical safety assessment to ensure the subject's health was not compromised over the course of study participation. For this reason, I would argue that it is acceptable to perform early termination assessments if a subject refuses to sign the new consent (as long as the subject agrees to those assessments) and once that is finished, the subject can be formally considered withdrawn from a trial. The one caveat to this situation is if the early termination assessment is a procedure that was changed from the start of the study....in that case I would say the sponsor should be contacted to see if the old ET procedure would suffice because the new assessment would contain procedures that the subject did NOT agree to have done (and doing these would be a big no-no).
As for the other options: choice 1 could be okay, but would likely require additional documentation to show why an ET visit was not done. Choice 3 would be the worst choice because a consent signature means the subject agrees to participate/complete a study and I feel that having a subject sign the form with the direct intention of discontinuing immediately afterwards violates the meaning of the consent signature itself. You may disagree with my opinion, and if so, I'd love to hear your reasoning, so shoot me and email or leave me a comment!
Oh, and by the way, the MOST important thing to remember if this situation arises, is to document the whole thing to death. I cannot overstate the importance of a clear explanation of this type of situation in the event of an audit.
When considering this, it seems there are three options:
1) Document the situation and let the patient leave without any early termination assessments because the subject is not a part of the new consent and hasn't agreed to any further study procedures
2) Document the situation, but proceed with early termination assessments if required by the protocol
3) Proceed with the new consent under the provision that the subject will sign consent, then immediately withdraw from the study.
After thinking about this for some time, I believe that option 2 is the best choice. Here's why: Some would argue that by declining to sign the revised ICF, the subject is withdrawing consent to participate in the trial, which is true. Also because there was a new ICF issued, the old consent is no longer valid and the subject is technically not participating under any ICF by the time they are presented with a new consent form. Thus any procedures done prior to the new consent would be done without the consent of the subject, and a big no-no. The previous two sentences are where my opinion differs.
By signing the original consent at the start of the study, the subject is agreeing to take part and follow all study procedures, including the early termination assessment. If a new consent is administered, the subject is still participating under the old consent and no further procedures may be carried out until the new consent is signed. However an early termination assessment is likely something that was required under the old protocol, and in almost every case, is a critical safety assessment to ensure the subject's health was not compromised over the course of study participation. For this reason, I would argue that it is acceptable to perform early termination assessments if a subject refuses to sign the new consent (as long as the subject agrees to those assessments) and once that is finished, the subject can be formally considered withdrawn from a trial. The one caveat to this situation is if the early termination assessment is a procedure that was changed from the start of the study....in that case I would say the sponsor should be contacted to see if the old ET procedure would suffice because the new assessment would contain procedures that the subject did NOT agree to have done (and doing these would be a big no-no).
As for the other options: choice 1 could be okay, but would likely require additional documentation to show why an ET visit was not done. Choice 3 would be the worst choice because a consent signature means the subject agrees to participate/complete a study and I feel that having a subject sign the form with the direct intention of discontinuing immediately afterwards violates the meaning of the consent signature itself. You may disagree with my opinion, and if so, I'd love to hear your reasoning, so shoot me and email or leave me a comment!
Oh, and by the way, the MOST important thing to remember if this situation arises, is to document the whole thing to death. I cannot overstate the importance of a clear explanation of this type of situation in the event of an audit.
02 December 2009
If clinical trials are necessary for new drug development, where are the participants?
PharmaTimes published an interesting article on clinical trial participation (or lack thereof) in Ireland, and while that is across the pond from us I think the ideas are probably universal. The article polled the "general public" (actual methods were not discussed) on the perception of clinical trials and the results were interesting. Basically, people do not participate in clinical trials because they either have: a poor understanding of what "clinical research" its or they are not willing to put themselves at risk by taking an investigational drug with serious or unknown side effects (Of course every drug has a laundry list of potential side effects, some quite serious, in the package insert, but how many patients read that before taking a medication?). The strange thing is that, in spite of this, people seem to understand the importance of clinical research in developing new or improved treatments for any number of illnesses. I have certainly experienced this first hand at the clinical research site side of things, and in my opinion the key to changing this trend is public education through a variety of platforms, including physicians (not just those who are clinical investigators).
All practicing physicians should advocate for participation in studies because the majority of the public does not have direct contact with a physician conducting a clinical trial, so what exists is essentially an untapped resource. This can be as simple as an informational flyer or a discussion in an exam room, but all doctors should understand what clinical research is as well as the importance of enrollment in these medical research studies.
Another option, which has been discussed at length recently, is social media. We as a society have only begun to scratch the surface of the far reaching potential of services like facebook, youtube, and twitter. While pharmaceutical companies struggle with appropriate ways to utilize these services, it should be a no-brainer for investigative sites. As long as IRB approval of an ad is in hand, sites should be tweeting their new trials, updating their facebook pages (you DO have a company facebook page, DON'T you?) with new studies (as well as useful links about clinical research...think centerwatch.com), and posting ads on youtube. From there these social media platforms should be posted, updated, and publicized as much as possible to increase visibility. While this is a relatively new advertising plan (compared to print ads, which are becoming antiquated), social media has already proven in many other industries to be a vital educational and marketing tool whose power should not be overlooked.
Read the Life Science Leader piece on clinical trials, pharma, and social media
All practicing physicians should advocate for participation in studies because the majority of the public does not have direct contact with a physician conducting a clinical trial, so what exists is essentially an untapped resource. This can be as simple as an informational flyer or a discussion in an exam room, but all doctors should understand what clinical research is as well as the importance of enrollment in these medical research studies.
Another option, which has been discussed at length recently, is social media. We as a society have only begun to scratch the surface of the far reaching potential of services like facebook, youtube, and twitter. While pharmaceutical companies struggle with appropriate ways to utilize these services, it should be a no-brainer for investigative sites. As long as IRB approval of an ad is in hand, sites should be tweeting their new trials, updating their facebook pages (you DO have a company facebook page, DON'T you?) with new studies (as well as useful links about clinical research...think centerwatch.com), and posting ads on youtube. From there these social media platforms should be posted, updated, and publicized as much as possible to increase visibility. While this is a relatively new advertising plan (compared to print ads, which are becoming antiquated), social media has already proven in many other industries to be a vital educational and marketing tool whose power should not be overlooked.
Read the Life Science Leader piece on clinical trials, pharma, and social media
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