Reflecting now on ACRP 2011 several months later, I wanted to share some of the valuable insights I gathered there. ACRP 2011 was an excellent conference, with more than 2100 attendees. Topics were wide-ranging, from business and finance to global challenges and ethics. As with many conferences, my major difficulty was choosing among the numerous offerings running concurrently. Here is a sampling from those I attended.
Carmen Gonzalez held a session as lively as she is, “La Sangre Latina: The New Force in Study Participation,” with many tips to helps you boost enrollment and retention of Latinos. Her surveys have shown that “Latino study participants are three times more likely to be unemployed, uninsured, or on Medicaid than U.S. averages for Latinos.” As a result, 82% of the participants, who are also more likely to be uninsured, did so just to access basic care for their chronic illnesses. Among other strategies, I learned that word of mouth from friends and Spanish language TV are particularly effective recruitment tools in Latino populations and that social media is less effective.
Given the economy, we’ll undoubtedly see more people volunteer for basic care, which presents troubling ethical issues. For example, some people may lie about their level of drinking, or past medical history, so as to meet inclusion-exclusion criteria. Others might take risks that they wouldn’t have under less trying conditions. As a Principle Investigator, I’ve always tried to be very attuned to my volunteer’s motives and understanding of risks, and even not to offer a study if I have concerns about it not being good for the volunteer.
Now that many trials are now being outsourced, I also attended several offerings on clinical trials in developing countries. Issues of ethics were again a significant focus, along with cultural sensitivities. There were good discussions of related questions: Are there different values? Who makes decisions? Are there benefits to the larger community? What is the impact of introducing new technologies or drugs that may not be available or affordable after a trial ends?
Fabio Thiers put a new twist on globalization. He had effective visual displays illustrating changing patterns in research activity globally, broken down by the type of indication. For example, CNS studies are increasing in the US, while cardiovascular and oncology trials and decreasing their US sites. The acceptability of placebo arms varies strikingly by countries and is generally the least accepted in France and Germany. All of these factors can help both sites and sponsors plan more effectively to remain competitive in the global market. The global industry trend is to have R&D be more visible and standardized, via registries, SOPs, and processes across sites.
Trials in India drew significant interest amongst attendees. While there are huge numbers of treatment-naïve patients, regulatory hurdles are major downsides; multiple agency approvals are required, and there can be difficulties over drug and supply imports as well. Getting a broker to navigate these supply problems and meet regulatory requirements is vital. The increased negative press attention over ethical issues and “slumdog trials” is shifting the placement of clinical studies away from India. So, too, are the ongoing fights between major multi-national pharmaceutical companies and small Indian generics manufacturers, centering around patent disputes. Immediately after the ACRP conference, I spent several weeks in India. While not directly involved in clinical studies there, the trip gave me the opportunity to meet with people and see first hand some of the logistical difficulties of conducting clinical trials in India.
According to Thiers, the EU is the big winner in the bid for attracting clinical trials. The EU is showing the most clinical research growth, projected to reach 46% of world market within a few years. India is not attractive for upcoming HIV trials, as they require the subjects to have been on other anti-retrovirals. On the other hand, Brazil is making a strong showing for HIV trials, given a baseline high level of care.
The globalization of trials can lead to confusion, as well as to added logistical hurdles in obtaining drugs, in the shipping of specimens, and of the reporting of labs in a timely and consistent fashion. For example, SAE reporting requirements are different under ICH than by the FDA; everything needs to be carefully spelled out so you are compliant with the regulations.
One welcome change in clinical trials is that studies of seniors are gaining in importance—for many of my trials, being older than 65 was an exclusion. This is, thankfully, changing. But you have to choose your words carefully here, so as not to offend by calling someone “old” or “elderly” when that doesn’t fit their self-perception. Retention can be a problem with senior subjects, as they may travel a great deal and be gone for extended periods. A very useful recruitment suggestion is to recruit by symptoms, rather than the disease name. Transportation may be a difficulty for these patients, as can very long, drawn out study visits, so plan accordingly.
Another major topic at ACRP was regulatory affairs. Once, again, there were many useful tips. Oversight was like a mantra. Sponsors must remember that they provide oversight of the CROs activities at the site level. CDER is focusing on the sponsor’s responsibilities—and again, there should be a SOP or delineation for everything. One recent trend is for the inspectors to do audits during a trial, rather than after it has ended, in the interest of patient safety. The choice of which study is audited now depends on the risks of the trial and vulnerability of the subject, and is no longer confined to top enrollers.
Balancing such serious sessions were social activities and opportunities for networking. The only slightly sour note in this well-arranged conference was the lack of internet capability—it is unfortunate that the exhibition center made the cost prohibitive.
ACRP was otherwise well-thought out and well-executed, with topics that spanned the gamut of topics likely to be of interest to the clinical trials professional. There truly was something for everyone. So, hope to see you next year at ACRP.
It seemed a perfect Indian summer day-an idyllic day to take a break to experience small-town America. I’d heard that the Damariscotta Pumpkinfest and Pumpkin Regatta were loads of fun, so hurried to take my son to witness a different era. We stood in the warm sun near the start of the pumpkin parade and watched amusedly as creative and funkily clad pumpkins drove by, along with vintage cars and fire engines.
The 4H club, leading a sunburned cow with hooves painted bright orange…
Then the Shriners came, cavorting on their go-karts. I didn’t understand the roller coaster contraption on top of the truck in their midst. As they neared, the cars careening around the tight circles, I instantly fretted—how do they not lose control and run into each other? I reassured myself that they were experienced, and tried to bring myself back to just enjoying the warmth and the uncommon sites. Besides, these guys were clearly having the time of their lives. Their truck said ”we ride so others can walk.” The worrier in me popped out again as one, and then the next, rode over their truck on the roller coaster, and then back onto the street. I breathed a sigh of relief. Then, as they passed us, the clowning go-kart guys looped back around the truck for another run, aiming to delight the crowd lining the streets. I turned to watch, and saw a go-kart lose control and flip over, and then the others plowed into it, unable to stop as they barreled down the rail. Though horrified, I ran over to see if there was anything I might do. As the troopers and bystanders pulled the kart off of him, I saw the back of a disfigured, bulging head in a rapidly growing pool of blood. I walked slowly back to my family, sickened by the scene and my helplessness, as the EMTs and others cared for the man…
We left, and drove down to the Audubon camp, one of our favorite places in the world. The view of Hog Island and Muscongus Bay nourishes the soul…
But the visions of the accident kept coming back. Before I went to bed, I checked the news and found that the Shriner had, in fact, died of his injuries. I felt sad, but also felt a wave of relief, knowing that there are many things worse than death…He had been doing what he loved, with such child-like joy and abandon. He was truly living in the moment when his life was extinguished.
Yes
but then right in the middle of it
comes the smiling
mortician*
Steve Jobs and others are right to say, “Live every day as if it is your last.” I wish I knew how, rather than always waiting for the other shoe to drop. So I hugged my son and husband, a little more tightly, and vowed to try and relearn.
*Lawrence Ferlinghetti
Pedestrians share the crowded, pot-hole pocked roads with motorcyclists, auto-rickshaws, trucks and buses, as well as an assortment of dogs and cows, and the occasional goat. There is the rank smell of sewage and piles of garbage balanced by spices and sizzling fried dough and meat from the sidewalk vendors. Destitute children and lame beggars contrast with the vivid colors of the rich fabrics worn by even relatively poor women, and the carnival like atmosphere of the pedestrian Mall Road.
Our hotel could euphemistically be described as “modest.” 
The students quickly adjusted to the spare, but colorful rooms, and to the routine of heating water for bucket baths, but had a harder time with Indian food and difficulties with reliable internet access. By the third day of paranthas for breakfast and some combination of roti with lentils, rice, and paneer in tasty sauces, the kids were ready to riot. Fortunately, the hotel staff were quite accommodating and broadened the diet to include chicken and mutton stews, though the recognizable body parts were a bit disconcerting. The students discovered that if they hiked ~45 minutes up the road to Old Manali, they could go to fancy restaurants catering to tourists with pizza, pasta, crepes, and a variety of ice cream dishes, accompanied by pop music or karaoke. They made a bee-line for “Drifter’s,” “Dylan’s,” and “Bella Vista” every evening thereafter. So much for our plans for evening bonding experiences and cultural activities for the immersion in India experience…
The immediate tasks for the weekend were to obtain Salwar Kameez “suits” for the girls and cell phones or sim cards. Buying clothes in India is a treat for many women. 
There is such a beautiful array of material, now with many lovely embroidered patterns on them. You walk around town, find the material that appeals to you, barter with the shop owner, then take the fabric to a tailor who measures the suit and sews it for you.
Obtaining a sim card was a bit more complex. Because of terrorist activity, in order to buy a sim card, we had to have additional passport photos taken and show proof of residency, as well as fill out several forms. Fortunately, we had Sunny, who capably guided us through this process and attested to our identities. Every hotel now also required copies of our passport. That reminded me of visiting Hungary during it’s communist rule.
While still exhausting, getting settled in, it was fun seeing kids' excitement and dismay. With the initial mundane tasks accomplished, we settled in for our work and study at Lady Willingdon Hospital and the villages.
I did, however, want to call my reader’s attention to this, particularly since there is currently a heated debate about the value of anonymity on-line. EpiRen’s harassment is a perfect example of the benefits of anonymity—more poignant since he blogged under his own name. Ren was careful to “clarify that none of the views presented in this blog (or anywhere else, really) represent the views of any of Ren's employers. Got it? Good.” Yet cigaRhett complained to Ren’s superiors, prompting them to threaten his continued employment.
It makes me feel ill that Rene has been bullied into silence. Maybe it’s sort of PTSD from similar past events in Cumberland. As I posted in Liz Ditz’s comments, Ren’s Epi Night School has taught me more about epidemiology than anything I learned either in med school or during my Infectious Diseases fellowship. He has a fine gift as a teacher, and the rare talent of being able to explain difficult topics in an engaging manner. The Daily Ren is a valuable news source and helps me keep up to date in my practice. EpiRen’s tweets are similarly an ongoing, real-time source of public health information, and he curates information from multiple sites I would otherwise overlook. Ren writes with humor and with passion about public health. He has been an ardent proponent of vaccinations. I have grown to find a sense of community as he and I and the #HandHygeine Team joust with the #pathogenposse. From my perspective, EpiRen and “The Germ Guy,” JATetro are the lynchpins of my staying current on public health, and this team is much more engaging than just reading CDC or CIDRAP reports.
Yesterday, the new EpiRen posted,
“Last day to print out or cache your favorite posts of the Epi Times. It goes down permanently at midnight tonight.”
As of last night, EpiRen has closed his sites. What a shame.
The response from Ren’s cyberfriends has been heartwarming, and perhaps good will come of this travesty:
The Skeptical Lawyer has joined the fray with an excellent post, “Lessons from EpiRen: do public employees have free speech rights?
PZ Myers, “Pharyngula,” has characterized cigaRhett’s posts as those of a litigious bully, who now, having been confronted, is attempting to erase his tracks on the internet. But the best characterization of the bullying behavior comes from Rhett Daniels' own threatening words.
A seasoned veteran of similar wars, Orac, has written about the consequences of blogging under one's own name. This is a timely issue, given the move by Google+ and ScienceBlogs to prohibit anonymity.Before “#Epigate” happened, the need for anonymity was carefully explained by Skepchick in her post, Does Google+ hate women? I highly recommend her article for valuable perspective.
My initial reaction to the breaking news was to want to enlist William Raillant-Clark and Kyle VanderBeek to help, given their recent success with getting internet troll David Mabus’ violent threats to scientists and atheists to be taken seriously by Montreal police. But EpiRen asked to not have a large internet outpouring to his employers and discouraged action.
I’ve been heartened by the support for EpiRen and free speech. I hope that EpiRen’s employers take to heart Skeptical Lawyer’s comments about transparency. And I would tell them that René Najera’s posts as EpiRen are not just frivolous social banter. EpiRen provides important, real-time news and an outstanding tutorial series on epidemiology.
As I was rereading the Epi Times last night, I noted an apt quote. To paraphrase Cesar Chavez, “Let us remember those who have been silenced by injustice; For they have given us life.
Prelude…or why am I doing this?
When daughter, Heather, was 15, she persuaded me to take her
and my son on a volunteer trip to India. It was transformative for all of us, fueling my interest in tropical infectious diseases and social justice issues, as well as my kids’ later career interests.
Heather has continued her interest in global and public health, and is now pursuing an MPH at U MD. As part of her work there, she put together this comprehensive summer program for undergrads, “Summer India: Global Health & Development,” and I was drafted as one of the faculty members, appointed “Visiting Senior Research Scientist” at the university, given my background in Infectious Diseases and clinical research, and that I had previously been to India. The other faculty were Mili Duggal, a PhD candidate and wonderfully down to earth, kind person, and Lis Maring (who was not able to join us until later into the trip), faculty in Family Life Sciences at U MD, and who has worked and taught in Varanasi, India.
The trip was logistically quite complex for a number of reasons. In addition to the didactic coursework—Heather put together an amazing syllabus—there were experiential and research components. The students were divided into three groups and rotated each week: observing at Lady Willingdon Hospital in Manali, joining village health care workers in assessing children’s health, or spending time at a rural health clinic in Jibhi, 3-4 hours from Manali. The final week was devoted to each student working on a research project of their choosing.
I helped arrange the research component, working with Dr. Philip Alexander, the director of the LWH, and Jayanth Devasundaram, an epidemiologist I recently met here in the states. Dr. Philip had asked for help in addressing their problem with tuberculosis, with many patients with drug-resistant (MDR) TB. We had only a sketchy plan before we left the states, and modified our approach as we went along, based on conditions we encountered there.
We set off!
The trip started a bit tenuously. I didn’t even get my visa until the day before, when my brother, aka St. George, was kind enough to wrest it out of Travisa’s clutches and deliver it to Mili.
I met the kids at BWI and was initially struck by their enthusiasim, and how YOUNG they all appeared, feeling OMG, what am I getting into? They were remarkably good sports on the trip though, which included the long flight, followed by a 9 hr wait in the Delhi airport, then a puddle-jumper to Kullu, 
which flew through a beautiful valley at the base of the Himalayas. We had to wait for some time in Kullu for Sunny and Heather to meet us—I guess there were more sheep blocking the road than they had counted on. (Sunny is a wonderful young man we met in Dharamsala 7 years ago, and he handled the logistics on the ground for all of us. We could never have done this trip without his guidance). But Sunny had a friend, Srita, who worked for Kingfisher and who was kind enough to ply us with chai while we waited. 
There is a “taxi mafia” at the airport, and transportation has to be made using their services. Four taxis and a hair-raising 2 hour drive later, we arrived in Manali and settled in for the duration...(to be continued)
There is good news today from the medical device section of the FDA, with the approval of the first test to quickly distinguish MRSA from MSSA (HT @EyeOnFDA). This new test, the KeyPath MRSA/MSSA Blood Culture Test, is said to differentiate between the two in about five hours after growth is detected in blood cultures.
So how much difference will this make in patient care and the MRSA epidemic? I suspect not much…
First, the test detects MRSA in blood cultures. While handy, most patients with MRSA do not have blood stream infections. Instead, they are colonized (just have it happily coexisting with them) or infected in wounds, sputum or, less commonly, in urine. Many people simply carry Staph, including MRSA, in their noses. This asymptomatic carriage and shedding of MRSA is what leads to outbreaks, and why many hospitals now screen high-risk patient admissions for the organism, or isolate such patients presumptively. So this test is unlikely to lead to much change in isolation practices. It might be quite useful, however, if it can rapidly detect MRSA in wounds.
If someone is seriously ill, most physicians will now empirically treat for MRSA, along with giving other broad-spectrum antibiotics, since the mortality of septic patients is quite high. Generally, after 24-48 hours, when culture results are initially available, an attempt is often made to narrow the spectrum to use more specific drugs. This reduces side effects and emerging antibiotic resistance.
Where the KeyPath MRSA/MSSA test reportedly has significant value is in its ability to do rapid susceptibility testing, important because there are major differences between many of the “community-acquired” MRSA and “hospital-acquired” strains. They report using a “Bacteriophage Amplification Technology,” which is well described by Drew Smith.
I will likely find this test of some use, as it will guide my therapy and lead me to narrow the spectrum of antibiotics I am prescribing up to a day earlier. I am a narrow-spectrum antibiotic kind of Infectious Disease physician. Some of my colleagues, whether because of their training or by having been burnt by experiences, tend to use very broad-spectrum drugs. This is especially likely to occur with more severely ill patients—even if there are no positive cultures—both because of genuine concern and because of fears of malpractice suits.
I don’t believe having this test will dramatically change practicing patterns, however. There is ample evidence that physicians don’t change their prescribing habits in response to data. In one widely cited study, 47% of docs made changes in response to susceptibility test results, but “but only 50% of the changes were considered appropriate.” In contrast, Berild, et. al. found 88% of their docs adjusted antibiotics, resulting in narrow spectrum use in 80% and a 23% cost savings. The findings of this 2006 Norwegian study were much more positive than others I have seen reported, or seen in my practice.
But the other factor arguing against this new rapid diagnostic test’s having great impact is the psychological need of the doc—a need that often seems to overcome reason. If a patient is better, many are loathe to change course—just in case, or “not wanting to argue with success.” Magical thinking, perhaps?
I can certainly see many uses for this new Bacteriophage Amplification Technique for antibiotic susceptibility testing. We can use all the help we can get in the fight against antibiotic resistance, and rapid diagnostics would be a big help. What kind of impact do you think this new KeyPath MRSA/MSSA test will have?
I was reminded last week of the Tom Lehrer admonition, “just don’t drink the water and don’t breathe the air.” That lead to the other Lehrer song, “Who’s next?”
In this week’s episode, the doom and gloom comes from food safety, brought to you by #ahcj11. The first panelist, Michael Taylor, deputy commissioner for food, Food and Drug Administration, set the stage, explaining the magnitude of the problem. The U.S. has 12 million shipments imported from150 countries. He explained that the FDA's role is to set standards to ensure accountability for both domestic and international products, but he placed the primary responsibility for ensuring safety squarely on industry. Unfortunately, the FDA’s efforts to improve safety standards are being stymied by budget cuts, as well as politics and the bizarre fragmentation of responsibilities.
Scott Faber, J.D., vice president, federal affairs, Grocery Manufacturers Association, countered that the new Food Safety bill provides some increased protection for consumers—for example, by giving the FDA access to industry records as well as the authority to require 3rd party auditors. The bill also gives the FDA the power to issue mandatory recalls.
Erik D. Olson, director, Food and Consumer Product Safety Programs, The Pew Charitable Trusts, stole the show, however, with his clear outline of the problems and the mixed improvements coming via Food Safety Bill:
Similarly, schools have somehow seemed oblivious to many recalls, and not complied, per GAO reports.
Taylor, the FDA deputy commissioner for food, spoke positively of Administration support for food safety in the budget; unfortunately, some in Congress—you can guess who—want to unimplement the Food Safety bill.
There are still many logistical hurdles to be overcome including better ability (let alone, authority) to conduct tracebacks. They are cumbersome and time-consuming, but have worked for items with one ingredient, like produce or meat. But there is no good system for tracking products with multiple ingredients. This is giving more impetus for food manufacturers to work with the FDA more cooperatively, a risk sharing arrangement.
One of the most shocking things I learned—there is huge hole in the system—meat and poultry are regulated by the USDA, not the FDA, and therefore are not included in improvements in the Food Safety bill. How irrational is that?
And 60% of produce and 80% of seafood is imported, with little oversight.
I’ve always enjoyed the CDC outbreak investigation reports and marveled at the ability to do tracebacks. Given the magnitude of the problem, their success is even more amazing.
I’ve reassured myself somewhat about food safety from the early polio studies, that showed that children from more affluent families were disproportionately affected.
Unlike many other illnesses, David M. Oshinsky notes “in the past, polio had been a disease of cleanliness.” Poor kids, from less sanitary environments, actually fared better, presumably from having built up some immunity.
(Photo by Judy Stone; Luang Prabang, Laos--suggest you enlarge)
So, while the Food Safety bill offers some hope, there are still huge gaps, especially with such a fragmented system. What’s a mother to do? I guess I’ve gotten much more fatalistic. Try to eat organically, at least where the most pesticide-laden crops are concerned. If you can, support local farmers who don’t use antibiotics or hormones, and who support free-range animals. Otherwise, if you think it will help, pray or lobby, whichever suits your beliefs, or assume an ostrich-like stance.
