These were only a few of the questions that arose following a survey conducted by the eClinical Forum last year measuring the global use of EDC in clinical trials—a follow-up to a similar survey conducted in 2001. Of course the world is a bit flatter now than it was then, and the facilitators expected that the data would reflect some significant changes in the industry.

Yet, when the final results were analyzed, what they revealed was still surprising. In particular, despite current pressure on the industry to connect health care and clinical trial systems, and to improve efficiency in care, treatment, and documentation for patients and trial subjects, clinical trials and patient health records still cited an 80% to 100% data input duplication rate.

An expanded view on the topic is available here.

Besides searching for opportunities online and on company websites, what are some other ways a candidate can go about a job search? Would you recommend cold calling a company or even stopping by in person?

Angela Lucas, Senior Clinical Team Lead and Recruiter at ClinForce

• Candidates should create a network to keep in tune with new employment opportunities.
• I suggest working with no more than three recruiters with whom you develop a strong relationship.  Keep track of where your resume is sent and by whom.
• Sign up on job boards that offer e-mail alerts based on your interests to keep you updated on available positions.
• Networking with colleagues: Some groups or even individuals create their own e-mail alert list to share new openings with one another.
• Join associations. Many professional associations’ post-employment opportunities for their members at national and local levels including websites, job fairs, trade shows, etc.
• Cold calling; though not unheard-of, it is a bit difficult.  Unless you are confident you can get past the gate keeper, I would refrain.
• I would not suggest stopping by in person. Many offices are not set up to accept walk-ins and usually, you are referred to look at their online postings.

Angela Roberts, Head of Recruiting Operations at craresources

• First, use industry specific information to find out what is actively going on and approach teams directly. For example, in our industry you are able to visit clinicaltrials.gov and see what trials are currently running in your favorite therapeutic area. Those trial listings will have contacts (CRCs, PIs, etc.) and there is nothing wrong with contacting those individuals directly! I would recommend sending a well-tailored e-mail with a copy of your resume. Then follow up with a rehearsed and professional phone call/voicemail. Be sure to clearly articulate why this trial is perfect for you—you will need your passion and excitement to leap off of the e-mail and be clear in your voicemail.
• Second, use your network! Don’t underestimate who you know. We have written an article which goes into detail on how to build, nurture, and leverage your network when looking for a position.

Safety has emerged as perhaps the core beacon guiding regulatory action and oversight today. It is well accepted that approval is in fact based on “a point in time” and our knowledge evolves over a lifetime–leading to expanded or restricted indications. A clear fourth hurdle has emerged as the true arbiter of access–reimbursement—based not only on regulatory approval (absolute effectiveness) but on principles of “value,” comparative (cost) benefit profile that includes both efficacy and safety. What appeared unreasonable only a few years ago, regulatory approval itself rooted in comparative benefit, now appears plausible. In other words, the lines between safety, regulation and access are progressively getting blurred.

In this milieu, the role of “safety” within a biopharmaceutical organization is rapidly evolving, and many facets of that evolution may be explored in successive posting. However, it is not my premise that drug safety reporting stands on the cusp of a major shift; what I believe is that the science of safety and comparative safety profiles, and models of risk management stand to penetrate ever deeper into the lifecycles of development and commercialization. One emerging case study of this shift appears to be the Sentinel project (Pink Sheet, Jan 23, 2012). It was always a possibility that Sentinel, once operational, may far extend the use of data collected for safety surveillance.

To a degree, FDAAA of 2007 and its overarching mission to improve drug safety provided funding for opening the gates to the house using a key marked ‘safety’; once open however, agencies and other parties can collectively wander into any room we want. These already, speculatively, include understanding real world usage of medicines and real world effectiveness, comparative effectiveness research, off-label usage analysis for pharmacovigilance purposes, head-to-head observational studies, and open phase-IV observational trials. In other words, a veritable field of dreams–if you build it, they will come! Sentinel could be the ideal laboratory for the agency to independently test the effectiveness of various risk minimization measures imposed on the industry. Of course, it remains to be validated whether the data collected in Sentinel has sufficient quality and fit for this purpose. But irrespective of Sentinel, similar analyses is being conducted, for instance by payors. For example, Medco’s head-to-head observations study (plavix/effient) to not only compare effectiveness, but to also collect information on HCP actions takes based on risk minimization measures. Interested parties across the pond are putting forward similar ideas around the eventual use of Eudravigilance data, post it full implementation by circa 2015.

As industry, we ought to accelerate discussion into what this means regulatory and safety capabilities within our own boundaries and what strategic changes are required for a scenario where safety, regulatory and commercial access/use are increasingly harder to tease apart.

Written by Sanket Agrawal, Global Regulatory Affairs and Safety, Amgen Inc., for Drug Safety Directions.

References

The Pink Sheet, Jan. 23, 2012, “Mini Sentinel Data Covers 126 Million Patients; FDA Weighing Potential Uses For Drug Industry.”

The prioritization of signals is still a highly controversial aspect of signal management.⁵ It is the opinion of this author that the process should be well documented and transparent to protect the organization from audit risk and to ensure the protection of the greater public health. There are a few examples of the type of decision support that is used to determine the priority of signals. The WHO uses a method which analyzes seriousness, unexpectedness, strength of disproportionality score, the temporal displacement of disproportionality score, age of the product, signaling in multiple countries, positive re-challenge, or existence of the signal term on a list of targeted terms.² These aspects of the signal are each evaluated and then an overall priority is placed on the signal that drives the formal evaluation of the finding (a methodology we will cover in next month’s Signal Evaluation blog entry).

Another known formal method of signal prioritization is from the United Kingdom’s regulatory authority the MHRA. They have borrowed the triage concepts from emergency rooms for their signal prioritization method. Essentially they analyze the immediate and high risk signal attributes first and allow those aspects to drive formal evaluation while lower signal attributes are postponed for formal evaluation until a later time.⁵ Their methodology results in the formation of a final priority score built of two main parts; Evidence score and Public Health score. The evidence score is an algorithmic score based largely on the strength of the disproportionality metric value, plausibility of causal relationship and the strength of the evidence provided.⁵ This is a different focus than the public health score which is compromised of the number of cases per year, anticipated health consequences, and the reporting rate in relation to the level of drug exposure.⁵ The combination of this score is used in an undisclosed manner to categorize the signal into a final category of High, More information required, Low, or No action.

Other companies have introduced software systems known as decision support systems into their organization to aid in the automated prioritization of signals. Researchers at Johnson & Johnson Pharmaceutical Research & Development, L.L.C. have introduced a systematic prioritization algorithm built into their signal management. In their methodology, multi-criteria decision analysis (MCDA) is incorporated into their signal detection tool so that a seamless evaluation of each signal occurs sending only those of highest priority into the formal evaluation process while others are allowed to remain in a holding pattern for further information.³

Regardless of the specific methodology selected, these works demonstrate the need of a formal, transparent, and reproducible signal prioritization aspect to our signal management procedures. In closing the ability for our field to make sense out to the vast amount of collected information continues to be a high priority. These systems and examples can aid in our continued protection of the public health and our collective companies.

Note: This post was edited by Gina Choi.

By Rodney L. Lemery, MPH, PhD, Vice President, Safety and Pharmacovigilance, BioPharm Systems, Inc.

References

1. Levitan, B., Yee, C. L., Russo,L., Bayney, R., Thomas, A. P. and Klincewicz, S. L.. (2008). A Model for Decision Support in Signal Triage. Drug Safety. 31 (9), pp. 727-735
2. Council for International Organizations of Medical Sciences (CIOMS). (2010). Practical Aspects of Signal Detection in Pharmacovigilance. Report of CIOMS Working Group VIII, Geneva .
3. Levitan, B., Yee, C. L., Russo, L., Bayney, R., Thomas, A. P., and Klincewicz, S. L. (2008). A Model for Decision Support in Signal Triage. Drug Safety, 31 (9)
4. Lindquist, M. (2007). Use of triage strategies in the WHO signal-detection process. Drug Safety, 30:635-7
5. Waller, P. (2010). An Introduction to Pharmacovigilance. Wiley-Blackwell. Oxford, UK

Some of the ongoing work funded by the EU is listed in an interim “special report” entitled “Monitoring implementation of the European Commission Communication and Action Plan for combating HIV/AIDS in the European Union and neighbouring countries, 2009–2013.”

One project, known as EUROPRISE; is promoting integrated research on HIV vaccines and microbicides and is exploring whether combined use of these two technologies can lead to more effective prevention. The partners have been involved in 31 clinical trials and have produced more than 200 peer-reviewed publications. The network, which has established collaboration between European and US researchers and with industry partners such as Novartis and GSK, has also played an important role in promoting a harmonized experimental approach and use of standardized reagents, says ECDC.

A consortium of 10 European partners known as THINC, coordinated by Leuven University in Belgium, has taken forward the development of a new class of anti-HIV drug, building on earlier research and working in partnership with the pharmaceutical company Tibotec. Successful negotiations have been concluded with Pfizer further development studies and clinical trials after project funding ends, says the report.

The NEAT network of excellence is implementing clinical trials for new treatment combinations, and has recently commenced a randomized clinical trial that will enrol more than 800 patients in 15 European countries—a trial of unprecedented scale in Europe. Coordinated by the Istituto Superiore di Sanita in Italy, it involves 41 partners and has promoted collaboration between European researchers on more than 21 clinical trials.

Overall, the money funds HIV prevention, increasing access to prevention, treatment, care, and support, especially in priority regions and for priority groups, research, surveillance, and monitoring and evaluation. And the money is substantial. In the research programme that ran from 2002 to 2006, the EU contributed 123 million euros to 41 projects on HIV-related research and 200 million euros to the European and Developing Countries Clinical Trials Partnership. During the first five years of the current programme (2007–2011), the total EU contribution to 17 HIV-related research projects was more than 82 million euros.

Most of this spending (94 per cent) was on development of treatment, vaccines, and microbicides, with a small allocation for basic science. Of an estimated annual spend totalling 27.1 million euros on this EU policy, research funding amounts to 16.4 million euros, says ECDC.

All very impressive. But the ECDC report is not entirely satisfied with the arrangements. “The balance of research funding does not fully reflect the priorities identified in the Action Plan,” it complains. Allocating research funding primarily to biomedical research may be understandable given the “inherent comparative advantages” of regional research initiative. But the result is that less funding has been provided for social and behavioral research and socioeconomic analysis—which merits greater attention, suggests the report.

Worse, the outcomes of the spending are less than satisfactory. Little evidence is available on the outcomes” of the “substantial” support to strengthen research capacity, networking, and collaboration. And worse still, “Commission engagement with the private sector appears to have had limited impact on antiretroviral pricing and treatment coverage or the coverage of HIV-related workplace programs.” ECDC argues for a tighter rein and a clearer direction—better-focused research and cheaper medicines. “The European Commission should develop and implement a strategy for engagement with the private sector, including the promotion of increased commitment by EU member states to the dialogue on affordable antiretroviral drugs,” it says. No such thing as a free lunch for industry!

Despite the positive financial news for the industry, “The Use of Medicines in the United States: Review of 2011″ report shed some light on a few disturbing current trends. The data revealed that seniors aged 65 and older reduced their prescription drug use by 3.1 percent last year.

At first glance this could be misconstrued as a positive — the older population is living healthier lifestyles and are reducing their reliance on prescription drugs. In reality, no such positive is evident. What is actually happening is that seniors are feeling the pressure of the slumping economy and are rationing their drug use instead of following their healthcare provider’s instructions. Needless to say this is an alarming development.

Even more worrisome is the fact that the most common group of drugs whose use is rationed or discontinued are those designed to treat hypertension. Keeping a constant and healthy blood pressure range is vitally important for everyone, especially the aging population who are already at a higher risk for heart disease and stroke.

Another disturbing trend linked to the struggling economy is a 4.7 percent drop in doctor’s office visits, while emergency room visits rose 7.4 percent — in increasing numbers Americans are forgoing scheduled doctor visits and treating their health on an emergency/as-needed basis.

The report is available at www.theimsinstitute.org.

There have been numerous articles written, blogs updated, whitepapers distributed, and tweets sent on the need to include social media in anything and everything you do communications wise..

When you assess where and how the pharma industry has entered into the social space, there are two main points: public relations and patient communities.

In the first, pharma companies set up social media outlets like Twitter and Facebook as a channel for redistribution of press articles. While larger brands find this an inexpensive way to push more information out to more people, it is counter to the basic premise of connectivity that social media stands for: creating community. There must be two things in place for this community to exist and for any social interaction to become fully engaged: trust and purpose.

The second area where pharmaceutical companies are participating in the social space is patient communities. These are sites and blogs established to bring together people with similar problems or illnesses and allow them to openly discuss issues, defeats, and victories. A place where, many times, the very essence of an illness will be exposed by the conversations in the community, thus providing a better understanding of the patients pharma companies want to reach.

An expanded view on the topic is available here.

Guido Rasi has now been executive director of the European Medicines Agency for nearly half a year, and one of the first indications of his most urgent priorities emerged on April 3 when EMA published its updated policy on conflicts of interests among the scientific experts and committee members it uses in its work.

“Since taking up the leadership of the European Medicines Agency in November, one of my main focuses has been on strengthening the ways the Agency deals with conflicts of interests and transparency,” Rasi said. “These issues will continue to be a major focus of the Agency’s work over the months and years to come.”

Surprisingly, the previous set of rules covering this area had been in effect since September 2011, but clearly they didn’t impress Rasi. The new document aims to give clearer guidance on the involvement of experts in academic trials and publicly funded research. Also, it aligns restrictions for the different roles in the scientific decision-making process and tightens the rules on grants from the pharmaceutical industry.

Today also sees the publication of a new policy on suspected breaches of trust, which sets out a procedure for how the Agency deals with incorrect or incomplete declarations of interests by experts and committee members. In addition, the Agency has introduced a policy on conflicts of interests of Management Board members. This largely follows the policy for scientific experts and committee members, while acknowledging the fact that the Board does not deal with specific medicines, according to the EMA press release.

Furthermore, the Agency has strengthened its policies on, and transparency over, potential conflicts of interests by taking the following actions:

• Publication of an online list of European experts and their declarations of interests in September 2011
• In January 2012, requesting access to declarations of interests submitted to medicines regulatory authorities in European Union (EU) Member States, so that the Agency can conduct cross-checks of the information provided at national and at European levels
• Publication of the risks levels for European experts in February 2012;
• Revision of the rules on conflicts of interests of staff members and publication of declarations of interest of Agency management in February 2012.

Experts cannot be involved in the Agency’s activities until they have submitted a signed declaration of interests and the Agency has assessed his or her risk level. Declarations of interests and risk levels are constantly kept up to date, the EMA claims.

Rasi has pinned his colors to the wall with this initiative. Time will tell whether the new approach bears fruit.