A clinical research freelancer’s life can be a bit solitary at times, so the annual ICR Freelance Forum provides a much-appreciated opportunity for freelancers to socialise and network with colleagues, and to learn from each other and from invited speakers. This year’s forum took place on November 3rd at the ICR headquarters in Bourne End, and was moderated by Rukhsana Shaikh-Zaidi, Chair of the ICR Freelance Steering Group.
There were five presentations, dealing with a variety of relevant and interesting topics. The presentation material is available to ICR members via the ICR website (
http://www.icr-global.org/community/forums/past-events-2009/).
A new perspective on records management
Eldin Rammell of RAMMEL Consulting Ltd, began his talk on ‘Records Management – Requirements and Legislation’ with a concern that this might not be the most thrilling topic ever! Judging by the amount of discussion his presentation generated, he needn’t have worried. Eldin led us to view records management from a new perspective: for once, rather than criticising sponsors’ documentation, we turned our sights inward, and considered what records management means to our own small business operations.
For example, must a freelancer have SOPs? Clearly, not all of us do. A straw poll indicated that while some of us have created a system of SOPs to rival a large company’s, others maintain that since we will follow our clients’ SOPs, we need not create our own. Perhaps unsurprisingly, no agreement was reached among the audience members on this topic. Should freelancers keep training records to demonstrate that they are qualified to take on their contracted tasks? There was no disagreement on the importance of training records, although without a QA department to nag us on a regular basis, freelancers may forget to keep these records up to date. Do our contracts with sponsors contain sufficient detail on our records retention responsibilities? We agreed that we should all examine this aspect of contracts more carefully, given the potential for major problems if roles are not clearly defined.
What project-specific documentation should a freelancer keep after a contract is complete? After all, most clinical research contracts state that all intellectual property will be returned to the sponsor after the study is finished. Eldin’s advice, however, is to keep sufficient documentation (eg, emails, other correspondence, and contracts) to show that you performed your work according to the contract and regulations. Why? Because there is always the possibility that a sponsor could bring (fair or unfair) legal action against you in the future. Thus, you should be able to reconstruct what you did and did not do, based on your records.
On a very different topic, many of us gave up any dreams we may have had of hiring employees, after Eldin introduced us to a breathtaking number of UK regulations applicable to employers, and we considered the documentation that would be required for compliance. We were, however, given an overview of a range of legislation applicable to us all, from the Data Protection Act to the Finance Act. We were surprised to hear that inspection of our tax records can now occur up to 20 years after an alleged event if fraud is suspected. That is a very good reason, indeed, for good record-keeping practices!
By the end of his presentation, Eldin had thoroughly convinced us that documentation is as critical to freelancers as it is to sponsors. GRMP (Good Records Management Practice) is important for regulatory and legal compliance, for risk management, and for business efficiency.
MHRA Inspections of Freelancers
Rukhsana Shaik-Zaidi followed with a presentation on ‘MHRA Home Inspections’ of freelancers, wherein she reported on one (anonymous) freelancer’s inspection experience. Many in the audience were rather taken aback to learn that home inspections could occur. Even worse was the news that the MHRA charges freelancers for the pleasure of being inspected at home, just as they charge sponsors for being inspected. The costs amount to roughly £2500/inspector/day. Clearly, it behoves us to check that our contracts with sponsors include reimbursement of such costs, including time spent preparing for, attending and following up on any inspection. There should also be no time limit on this clause, as an inspection could happen any time in the future.
The EMEA normally gives about two months warning of an impending inspection. What should a freelancer expect? First of all, be aware that the inspector may not understand the relationship between a sponsor and freelancer, so be ready to explain this, and have a sponsor contract that delineates responsibilities clearly and completely. Be able to show SOPs that describe the work you conduct for the sponsor. Whether the sponsor’s SOPs will be followed or your own, this needs to be stated in a study document. If you have your own SOPs, be sure that your ‘SOP on SOPs’ states how often the SOPs are reviewed or revised, and be sure you comply with your own rules. Beware that once the inspectors are in your office, they may change the scope of the inspection to cover any aspect of your work, at all.
What is the likelihood of a freelancer being inspected? Normally this would only occur under two scenarios: as an extension of a sponsor inspection (in which case the freelancer is more likely to be invited for an interview at the sponsor’s office), or if the freelancer undertakes a critical specialist/niche role for a sponsor (in which case the inspection might, indeed, be at the freelancer’s private office). Since inspectors are taking a ‘risk-based approach’ to inspections and are currently not targeting freelancers, the statistical likelihood of any of us getting inspected under normal conditions, is probably ‘vanishingly small.’ (This does not, however, release us from our responsibility to comply with GCP.)
International regulatory update
Rukhsana Shaik-Zaidi also presented an update of international clinical trial regulations, which can be found among the day’s presentations on the ICR website. Readers are reminded that news on international regulations can be found in CRfocus. Also, if you register with the MHRA website (or several other national regulators), you can receive regulatory updates by email. And finally, for quick access to 1,100 regulations on human research from 92 countries, you can visit
www.hhs.gov/ohrp/international/HSPCompilation.pdf, from the United States Office for Human Research Protections.
Medical update: Surrogate biomarkers
This year’s Medical update was presented by Guy Oliver, Senior Medical Development Advisor, Cardiovascular & Metabolism at Novartis Pharmaceuticals UK Ltd., who managed to make a complicated topic seem clear. Guy began by defining terms: a biomarker is anything that can be measured in the body, such as blood pressure, heart rate, cholesterol levels, and countless others. Surrogate biomarkers (SBs), then, are a subset of biomarkers that give an indication of what other, less readily measurable bodily processes are doing, including disease processes. A well-known example is cholesterol; high levels in blood is known to be associated with a number of chronic diseases.
Surrogate biomarkers are extremely valuable to the pharmaceutical industry. They are used in the majority of clinical trials. This is because they provide a quick response to a medical research question, rather than the sponsor waiting for a long-term outcome like cardiovascular events or death. SBs can also indicate, for example, whether there has been a change in the target organ during a study. The resulting benefits include that a study can be conducted with a smaller sample size and can be completed in less time and for less money. Studies can be also designed so that individual intermediate effects of the study drug can be studied one at a time.
So far, so good… but here begins the challenge. To be considered as an SB, a biomarker must:
- Have a biological rationale
- Be backed up by animal and in vitro data
- Have a proven correlation between its concentration and a relevant clinical outcome
- Be supported by data from clinical research showing that treatment effects on the SB lead to a change in that clinical outcome
Specialist regulatory authorities are extremely strict in defining which biomarkers can be used as SBs in a clinical trial. Getting it wrong can be very expensive, as was recently experienced by a large pharmaceutical company, which reached the end of a 25,000 patient study only to find that their chosen SB was not specific enough to enable them to draw the desired conclusions. Another example of difficulties with SBs is the question of statins. Although the results of clinical trials on statins have been helpful overall, studies have had mixed results. Clinical efficacy of a statin is often related to the drug tested, and not just lipid reduction. Yet another example is the use of diuretics in lowering blood pressure. In this case, not only might the study drug itself be related to health outcome, but also the dose given, and these factors may not even be linked to the SB, blood pressure.
In summary, Guy demonstrated that the importance of SBs is increasing. SBs are most useful in early phase studies, and they will never entirely take the place of larger later-phase studies, although they will augment them. At best, SBs enable greatly increased productivity and lower costs per study. The push is on to find ever better and more relevant SBs.
Clinical Research Networks & their impact on studies
Clare Morgan, Director for Industry at the National Institute for Health Research (NIHR) Clinical Research Networks (CRN) Coordinating Centre, rounded off the day’s presentations with an overview of the NIHR Clinical Research Networks, and their impact on clinical research in the UK. In 2006, the UK Department of Health made a commitment to build up the infrastructure in the NHS to support clinical research. The resulting NIHR (
www.nihr.ac.uk) is a virtual organisation with a goal of helping sponsors to reach investigators to conduct their clinical trials, and to facilitate other research factors. Funding has been provided to organise topic specific networks, beginning with support for Cancer studies from 2001, then Mental Health, Diabetes, Stroke, Dementias and Neurodegenerative Diseases, Medicines for Children, and Primary Care studies in later years. Recently, the Comprehensive CRN has been launched which meets the remaining medical needs. Currently, the NIHR is increasing its medical device investigator network.
Advantages of the NIHR CRN for sponsors include easy-to-reach investigator networks and a single point of access to the NHS infrastructure. NIHR CRN is, in fact, an intelligence service. Clare invited us to check the organisation’s website for more information.
The organisation publishes quarterly performance metrics and collects case studies in order to assess the success of their support to the industry. One interesting statistic is that, of the NIHR sites recommended to sponsors, 24% were non-productive at the beginning of the self-assessment, and that number is now down to 4%.
The NIHR CRN has created an industry costing templates to provide sponsors with UK investigator and pharmacy staff hourly rates, overheads, capacity building and geographical variation in these costs, all in aid of increasing transparency to sponsors wishing to conduct studies in the UK.
Clare explained that investigator inclusion in the networks is voluntary. Many studies are conducted in the UK outside the networks. Thus, use of the NIHR CRN is not required for sponsors, but is simply a valuable resource. It must also be said that before the NIHR CRN will allow a sponsor to access the networks, the CRN must ‘adopt’ the sponsor’s study. This is done on the basis of a draft protocol. (So far, out of 278 studies submitted to the NIHR CRN, 17 were not adopted.) Clare’s advice is to submit a draft protocol as early as possible and discuss this with the network, in order to get access to the CRNs in a timely manner.
Other initiatives include a streamlining of the NHS permission process, called NIRH CSP. The NIHR CRN is building up a body of research nurses and other study staff. We wish Clare and her colleagues success in this important initiative.
Final thoughts
As stated at the top of this article, freelancing can be a rather solitary existence at times. We have nobody to moan at by the coffee machine in our home office. We have no built-in Regulatory, QA, Operations, Marketing etc. departments to consult. So, the value of the ICR Freelancer’s group and annual forums cannot be overstated. This year’s meeting was attended by new and experienced freelancers, and we all benefitted from each others’ support, some very stimulating discussions, and from the excellent presentations.
The Freelance Steering Group is currently looking for new members. If you are interested in getting more involved, or have other questions, please contact Rukhsana Shaikh-Zaidi via the ICR office.
