Delays in clinical studies hurt
How do we get study timelines back on track?
Check it out… http://www.rxtrialsinc.com/our-blog/
Even the FDA is “De-cluttering”
Oprah, House and Garden TV, home magazines; they are all hot on the de-clutter bug. Even the FDA is stepping in. Last Wednesday FDA announced that many unapproved cough/cold and allergy medicines would be removed from the market. http://www.fda.gov/downloads/ForConsumers/ConsumerUpdates/UCM245228.pdf
The manufacturers of these products have 90 days to quit manufacturing the drugs and 180 days to cease shipments. After perusing the list of unapproved drugs, I noticed that while I remember a few from my childhood, most of these drugs are very old. Most were marketed prior to legislative requirements for demonstration of safety and efficacy. Often we forget how relatively new drug legislation requirements are. The mandate sounds dramatic, but I consider it a matter of the FDA de-cluttering; something I for one applaud. The cough/cold and allergy cadre of drugs deserves some attention. Not because some bad folk choose to make illegal drugs from the decongestants, but because they often have the potential for serious side effects. Who hasn’t taken a whopping dose of something for cold relief and either didn’t sleep for a day, or slept for a day or more? Keep going FDA. It may even shame me into de-cluttering my medicine cabinet.
Risk Definition for Device Recalls
It’s all about risk definition for device recalls
A recent article in The Archives of Internal Medicine entitled Medical Device Recalls and the FDA Approval Process, reviews and challenges the apparent lack of device class designation linkage to recall risk.
http://archinte.ama-assn.org/cgi/content/full/archinternmed.2011.30
Classification of a new device is based on risk and novelty. Classification of recall is based on risk to the patient. The study concludes that most of class I recalls, or high risk of death or serious health problems, are associated with class II devices. The article then concludes that these class II devices need more regulatory oversight.
Part of the problem is the assumption that class definition for devices are boxes and not linear gradients. I like to draw the analogy to skiing. A blue square slope can actually be light blue or very dark blue. The same holds for devices. Some class II devices do require clinical data. Trying to push the class II devices into PMA requirements increases regulatory burden, not to mention the increased difficulty in obtaining funding for these types of technology. Both result in a lack of treatment options for patients and their Physicians. Overall, there will always be more regulatory recalls for class II devices as there are more class II devices on the market. Also, some relatively simple, or low risk devices are used for life saving indications. Wouldn’t improvement in error reduction be a better approach? This involves FDA oversight of class II devices, which is already in place. Working within the system seems a simpler approach than change in regulations.
Barack’s Goal?
Goal of Barack’s Memo???
Recently our President, Barack Obama, issued a memo asking Dr. Amy Guttmann, chair, Presidential Commission for the Study of Bioethical Issues, for a review of human subjects protection.
This all stemmed from the recently discovered information regarding a study that the US Public Health Service conducted in Guatemala. While I don’t disagree that the matter deserves some attention, I feel the tasks requested require some review.
1. Convene a Panel – Sounds like a good start to any complicated issue
2. Thoroughly review Federal regulations and international standards to determine if they are adequate – When I think of all the time spent to develop and re-review Federal regulations and ICH; it’s hard to believe that a panel will find a gap in their given 9 month time period. I wonder how many people read ICH E6 on a daily basis. I have to admit; rarely a week goes by without me picking it up. I wonder if they will include the Declaration of Helsinki, as FDA doesn’t. Which reminds me, don’t we have at least two Federal bodies that do this as a day job?
3. Conduct a thorough fact-finding investigation into the specific Guatemalan study – What do we say here in Indiana about closing the barn door after the horses have left? Or is it cows? At any rate, I understand the intent, but so much time has passed, I’m not sure this will add value.
4. Seek insights and perspectives of international experts (include a Guatamalan) and have a meeting outside the US – Sounds like a good approach, but again, is this an ICH junior? Will individuals from FDA, OHRP and ICH be excluded to get a truly unique view?
This is a serious revelation that deserves serious attention. I fear it is duplicative at a time when we don’t have enough time and resources to do a job once. Anyone want to take a bet that not much is found in this mission?
Human Experimentation
Human Experimentation – It has not been that long…
I am shocked, that people are shocked by the press releases and apologies last Friday.
Web link: http://www.nytimes.com/2010/10/02/health/research/02infect.html?_r=1
The problem is that gonorrhea and syphilis are hard to culture, so it made sense to make prisoners in Terre Haute, IN useful by injecting them with the disease and then see if anything worked to cure it. Fortunately the study was stopped because it was just too hard to infect the prisoners, I mean, “volunteers”. Realizing this wasn’t a good thing to do to US citizens, we headed to Guatemala to conduct syphilis research on some more prisoners, I mean, “volunteers”. Surely this was during the time of the Tuskeegee study which involved infecting or using known infected African American prisoners. The research subjects were not treated in order to better understand syphilis disease progression. (Even after treatment was available) Actually the Terre Haute and Guatemalan studies were conducted during 1944-1948. Apparently while we were over in Europe giving the Nazis a talking to; we were conducting our own human research right here in the US, with federally funded dollars. I’m not sure the general population has experienced tremendous ethical evolution over the past 60 some years. More importantly, appropriate checks and balances have been put into place. Although, interestingly, one could argue that a separate review by the peers of your institution are not exactly independent. I commonly get asked, “If I am paying your IRB for a review, won’t that generate a conflict of interest?”. Quite the opposite. You are paying for an answer, not always the one you want, just an answer. Always some room for discussion, learning and improvement…..
Frustration with IRB review timelines
I noticed that Outsourcing Pharma had a blip on Investigators’ frustrations with IRB review timelines. See below to a link to the full article:
http://www.outsourcing-pharma.com/Clinical-Development/IRB-delays-a-frustration-for-investigators
The thought that an IRB efficacy study was needed, gave me pause for another thought. AAHRPP publishes IRB stats on an annual basis; so I perused the 2009 numbers. Per their data, seventy five percent of organizations have their own IRB. This sounds reasonable to me. Fifty three percent of these IRBs rely on outside IRBs for additional support, again, seems reasonable. Now here is where it gets tricky – Seventy two percent of these IRBs outsource less than ten percent of their workload. I wonder why only ten percent? Then I looked at the workload. The average IRB oversees about 400 protocols. Mean time from submission to approval is 48.8 days, although mean time from submission to review is 25 days. It appears that many Investigators are not getting the IRBs what they need to approve the study? The part that amazed me was the IRB organization staffing. On average, each full time equivalent (fte) employee is managing 139.8 protocols. Doesn’t that sounds like an amazing amount of work? While almost all the organizations noted that the process was improving, 87.6% reported that the workload was increasing. One last note, it appears that as the number of protocols per organization increases, the number of deviations reported per protocol decreases. I’m not sure how that could make sense?
Sounds like too much to do with too little time for me. As the Pharma Industry increases their outsourcing, why don’t the IRBs?
AAHRPP 2009 report
http://www.aahrpp.org/www.aspx?PageID=354
Check out OHRP training videos for IRBs
Have you seen the OHRP training videos on YouTube?
http://www.youtube.com/watch?v=GHtIbdLkSwU
What a great idea; and with an average of a 1,000 views, I guess many of you agree. It’s a great way to train new board members, PIs and the community about human research. The topics cover IRB membership, Informed Consent Requirements, Unanticipated Problems and more. Okay, I’ll forgive OHRP for not being able to spell “principles”, “priciples”. They even helped me to better explain the process to my colleagues. If you haven’t seen them, I highly recommend a view. I hope this process continues as I feel it is a great way to get information out to the research community. I’ll give it a thumbs up.
Ethics of Safety Studies for Marketed Drugs
Ethics of Safety Studies for Marketed Drugs
Even the Average Joe couldn’t have missed the discussions regarding the safety risks of Avandia. FDA is again in a tough spot and looking for answers. Traditionally, Industry was not to make safety claims about drugs, just a line listing of adverse events seen during clinical evaluation and after market. I agree with the Institute of Medicines assessment that, while the ethical considerations are perhaps more complex, they are manageable. The current system of oversight by FDA, IRB, Data safety management board (DSMB) and the Principal Investigator are the key. The study design needs to be scientifically sound (nothing new). The evidence threshold for stopping the study needs to be clearly defined (nothing new). The informed consent process is very important to protect the rights of the subjects (nothing new). Perhaps the issue is an increased focus on the risk benefit balance? Or is it getting used to the prospect of a safety endpoint versus an efficacy endpoint? Regardless, it all points to the need for transparency, open discussion and compliance.
IOM letter hyperlink: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM218595.pdf
IRB Administrator as Chair
It comes back to matching skill sets for increased efficiency. Odds are the Board chair was chosen, or elected, based on their leadership skills. Or, was this person chosen based on their keen ability to organize documentation per standard procedures to ensure compliance and reduce error rate? The Chair role and Administrator role are very different tasks requiring different skill sets. While perusing the warning letters to IRBs, one finds that the gaps are the ability to operate consistently in compliance with Federal and State regulations. The devil is in the details and that is where the Administrator lives; not the Chair. At Pearl IRB the Administration role is specifically separate from the Chair role to ensure efficient, ethical reviews.
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