Thursday, November 17, 2011

Swapping Germs to Beat C. diff?

Maryn McKenna has a great new post up on Scientific American, "Swapping Germs," about Clostridium difficile, or C. diff colitis. She talks about fecal transplants, effective but rarely used therapy, given the "ick" factor.

Often having a different perspective, I have added my own, slightly different take on fecal transplants.

Hope we'll have an interesting conversation and stimulate progress in finding treatments!


Thinking about going to ACRP in 2012? A recap of ACRP 2011

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-na├»ve 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.