 European editor, phone +44 1244 538583, philipward1@btconnect.com

Philip Ward

	Fraud prevention requires good research governance, clear peer review of activity, and mechanisms in place to investigate any allegation, and regular review of data and investigation of suspicious data, according to an experienced UK clinical researcher. Encouraging a whistleblowing culture, monitoring reports acted on by sponsors, understanding that mistakes can happen, and an open policy to “own up” are also vital.

	“Fraud seriously undermines the integrity of clinical research as a whole,” says Steve McSwiggan, PhD, deputy director of the Edinburgh Clinical Research Facility at National Health Service (NHS) Lothian. “The onus must be on all staff to raise any suspicions with a line manager or superior.”

	Clinical trial fraud is more prevalent than is thought, but is still rare, he added. The literature is littered with examples of fraud, despite most cases being dealt with in-house, and fraudsters tend to be lone workers or those who are so exalted that their work cannot be challenged.

	The consequences include damage to an individual’s reputation, damage to an institution’s reputation, erosion of scientific trust, dangers for patients (data used may lead to unsafe medications being licensed), and denying patients access to potentially useful treatments, according to McSwiggan, who was formerly the head of commercial research services at the Tayside Medical Science Centre (TASC), University of Dundee/NHS Tayside, UK. Furthermore, the time spent validating data increases costs and reduces the time spent on building new knowledge, and fraud leads to returned fees/grants, delays in review, cost of investigations, reanalysis of data, etc.

	McSwiggan believes it’s important to distinguish between fraud (use of deception with the intention of obtaining personal gain, avoiding an obligation or causing loss to another party) and research misconduct (fabrication, falsification, or plagiarism in proposing, performing, or reviewing research, or in reporting research results). In the UK, the most relevant legislation is the Medicines for Human Use (Clinical Trials) Regulations Statutory Instrument (2004, No. 1031), and the legislation for Clinical Trial of an Investigational Medicinal Product (CTIMP), which lays down 14 principles and conditions of good clinical practice (GCP).

	McSwiggan, who spent six weeks treating Ebola patients in West Africa in 2015, noted that other types of clinical trial fraud include forging (invention of false or misleading data), cooking (only analyzing data that supports a hypothesis), trimming (smoothing out data), misuse of statistics (use of improper techniques), and irresponsible authorship.

	Determining a local approach that works is important, he continued in his presentation posted on the TASC website (view 

). For instance, NHS Tayside has a whistleblowing policy, code of corporate governance (including fraud standards), and a fraud liaison officer. The University of Dundee has a code of policy and procedures for investigating and resolving allegations of misconduct in research and a whistleblowing code.

	To illustrate his key points, McSwiggan gave details of three notable case studies. Evidence suggests these are not isolated cases of misconduct, McSwiggan pointed out. The Commission on Research Integrity in Washington found in 1996 that 36% of doctoral and post-doctoral students were aware of an instance of scientific misconduct, and 15% were willing to do whatever was necessary to get a grant or publish a paper. A survey of members of International Society for Clinical Biostatistics in 2000 revealed that 51% of respondents knew of fraudulent projects.

	A review of 650 FDA inspections conducted between 1998 and 2013 led to 57 official actions. There were 22 cases of falsified information, 14 cases of researchers who failed to report adverse events, 42 cases of violations of the trial’s protocols, 35 cases of record-keeping errors, and 30 cases of researchers who failed to protect patient safety or to acquire informed consent.

Articles

Expert outlines approaches to preventing fraud in clinical research-a more prevalent problem that many believe.

What Can You Do to Prevent Clinical Trial Fraud?

European Federation of Pharmaceutical Industries and Associations

) has provided further evidence of the potential health risks posed by the upcoming relocation of the European Medicines Agency (EMA).

	In a statement, EFPIA says its latest survey underlines the scale and importance of the issues posed by the Brexit discussions and shows how much Europe’s integrated supply chains rely on the U.K. The key findings are as follows:

	• There are over 1500 clinical trials being conducted in multiple EU member states that have a UK-based sponsor. Over 50% of these trials are scheduled to continue beyond March 2019.

	• 45% of EFPIA members expect trade delays if the U.K. and Europe fell back to WTO rules. To prevent these delays, the EU and UK should agree a comprehensive agreement that ensures maximum alignment between EU and UK pharmaceutical laws, it states.

	• Over 12,000 centrally authorized marketing authorizations (MAs) for medicines will require a separate MA in the U.K. in order for the medicine to be prescribed to patients. Approximately 17% of centralized MAs are held in the UK.

	• Over 2600 final medical products have some stage of manufacture based in the U.K.

	• 45 million patient packs are supplied from the U.K. to other European countries each month. Over 37 million patient packs are supplied from the rest of Europe to the U.K. each month.

	“The survey underlines the scale of the task ahead,” commented EFPIA Director General Nathalie Moll. “For life-saving and life improving medicines, the EU and U.K. cannot afford to wait any longer to ensure that the necessary cooperation on medicines is in place from the day the U.K. leaves the EU.”

	The findings emphasize the importance of scientific research collaboration between the U.K. and EU, according to EFPIA.

	“Even in the context of the Brexit negotiations, where all sectors are looking for clarity on the future, it is important to recognize that the medicines sector is different. The medicines we make impact directly on peoples’ health,” she said. “Securing ongoing cooperation on medicines regulation between the U.K. and EU is the best way of ensuring that patients across Europe continue to have access to safe and effective medicines.”

	A summary of the EFPIA survey results is available 

EFPIA Voices Fresh Concerns on EMA Relocation

	European Union (EU) member states are due to select a new host city for the European Medicines Agency (EMA) on November 20, 2017, after which the EMA will have just over 17 months to conclude its move and start operating in its new HQ by the end of March 2019, according to a statement issued by the agency on November 7.

	EMA admits the relocation will be a challenging task, made even more complex by the “ambitious timetable” determined by the withdrawal of the U.K. from the EU. Effective collaboration between the agency and the new host country will be essential. Furthermore, EMA says it is committed to giving stakeholders and the public full visibility of the relocation project, and in early December it will make publicly available a monitoring chart that tracks the progress.

	According to the statement, “The most pressing issue that needs the immediate attention of EMA and the host country is the agency’s new premises. Many administrative steps need to be taken before work on the new building can begin.”

	EMA’s building plans need to be approved by the relevant local authorities, as well as its own management board and the EU budgetary authority. This process typically takes between six and eight months. Fitting out the new premises is expected to take between 12 and 15 months. Also, schools for around 600 children of EMA staff members, and affordable, good quality housing for up to 900 households must be found.

	EMA has pledged to provide further updates on the implementation of its business continuity plan as they become available.

Decision on EMA Relocation is Due on November 20

	The considerable uncertainty caused by Brexit is proving a goldmine for conference organizers, it seems. The Drug Information Association (DIA) is the latest group to put together a meeting about this hot topic.

	“Brexit will have a considerable impact on the regulation and supply of medicines to patients,” noted the DIA in a statement. “With the time frame for Brexit fast elapsing, governments, regulators, companies, healthcare systems, and patients are all seeking to prepare for the “known unknowns” and to brace for the “unknown unknowns”. However, information is scarce and not always accessible or confirmed.”

	At its meeting to be held in London on December 8, DIA plans to bring stakeholders together to share their knowledge about operational and strategic measures being taken to prevent or minimize the impact of Brexit.

	According to the organizers, “With the clock ticking, stakeholders will consider explicitly in this conference the dimension of time in shaping what opportunities for action companies-and indeed all stakeholders-must consider.”

	The closing session, called Brexit time check: "what’s next for medicines?”, will be chaired by ACT columnist Peter O’Donnell. The aim is to investigate the broader level vision of what’s coming next in the Brexit schedule of change.

	For the full program and further details, 

DIA Jumps on Brexit Bandwagon

	Information about more than 50,000 clinical trials is now available on the European Union (EU) Clinical Trials Register.

	The register contains data on 31,456 current trials with a EudraCT protocol, of which 5,048 are clinical trials conducted on subjects of less than 18 years of age. It also presents details about 18,700 older pediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

	The register, which covers studies that started after May 1, 2004 allows users to search for protocol and results information on both interventional clinical trials that are conducted in the EU and the European Economic Area (EEA), as well as clinical trials conducted outside the EU/EEA that are linked to European pediatric medicine development.

	It also maintains a list of patient/consumer organizations who may be able provide information on clinical trials within various disease areas. These are organizations that regularly work with the European Medicines Agency.

	For more information about the initiative, 

EU Trials Register Now Holds Data on Over 50k Studies

	The Swiss Research Network of Clinical Pediatric Hubs (SwissPedNet) is seeking to promote clinical research in pediatrics in Switzerland.

	Along with the Swiss Association of Paediatrics, SSP/SGP, SwissPedNet has issued a request for study proposals in pediatric health services research, and has set aside 120,000 Swiss Francs (around $121,000) to fund the initiative. Clinical research includes all investigations relating to patients seen either in private practices or clinics or both.

	Switzerland’s five university children’s hospitals (Basel, Bern, Geneva, Lausanne and Zurich), as well as the three children’s hospitals of Aarau, Lucerne, and St. Gallen, set up SwissPedNet in 2012. Its task is to promote, facilitate, coordinate, and conduct clinical trials devoted to children, ranging from newborns to adolescents, in all pediatric disciplines. The ultimate goal is to enhance clinical research in paediatrics, both by supporting pediatric clinician scientists to foster their commitment to high-quality clinical research and by encouraging increased acceptance in the community of trials in children.

	On November 20, 2015 the EOC Ticino’s department of pediatrics became the ninth clinical pediatric hub of SwissPedNet. In addition, the Swiss pediatric registry center at ISPM in Bern and SwissPedPha, the platform for pediatric pharmacology, are ordinary members of SwissPedNet.

	SwissPedNet receives federal funding in the framework of the roadmap 2017-2020 (

), and is closely linked to the Swiss Clinical Trial Organisation SCTO and its network of CTUs (www.scto.ch).

	The submission deadline for new proposals is February 28, 2018. 

Swiss Look to Expand Pediatric Trials

	The two ends of life can be viewed separately, but they have many common elements like frailty or vulnerability, and these shared aspects mean that geriatric and pediatric drug development should be viewed together, according to the European Forum for GCP (EFGCP).

	This philosophy has inspired the Children’s Medicines and Geriatric Medicines Working Parties of the EFGCP to organize a joint meeting, called “Multi-Stakeholder Workshop on Facilitating Medicines Development for Youth and the ‘Young at Heart’: Learning for Intergenerational Strategies,” to be held in London on 21 November.

	“The development of drugs is evolving and much effort is being put into understanding in special populations like children and older people,” noted a statement from the organizers. “The agenda reflects important topics like the special ethical considerations that can affect the informed consent process, evaluation of the safety parameters which is dependent of the adequate reporting of adverse events, and interpretation of the adverse drug reactions and proper use of modelling of simulation to bring value to the drug development process.”

	The objective is to share challenges, to detect possible synergies, and to learn from each other to improve and facilitate high quality ethical clinical research and drug development for these populations across Europe, they added.

EFGCP Gives Priority to ‘Two Ends of Life’

	The Austrian capital, Vienna, has reportedly joined the growing list of frontrunners in the keenly contested race to secure the future head office of the European Medicines Agency (EMA) after the U.K. leaves the European Union (EU) in March 2019. Stockholm, Copenhagen, Amsterdam, Barcelona, and Milan are thought to be the other leading contenders, but a final decision is unlikely to be taken until November in a secret ballot of the EU Council of Ministers.

	Austria’s health minister Pamela Rendi-Wagner and Vienna’s financial city councillor Renate Brauner presented their application to host the EMA in Brussels on Sept. 11, according to a report in the 

, the U.K. daily newspaper. The contest is now particularly fierce, with 19 cities, including Vienna, vying to become the new home of the EMA, it noted.

	The EU Commission was set to examine all applications by the end of September, but according to diplomats, there will be no shortlist. The latest estimate suggests the cost of moving the EMA out of the U.K. will be around £521 million ($705 million), which is £163 million ($220 million) above the initial estimate, the 

	“The EMA has calculated the cost of moving its operations and staff, and paying off the remainder of a locked-in lease that runs until June 2039, at more than half a billion pounds. Officials previously estimated it would run to £358 million,” the report continued. “This figure includes £401 million to pay off the rest of the lease, £34 million to kit out its new home, £47.4 million for relocating the agency’s 890 strong workforce, and £21.7 million on IT and audiovisual equipment and meeting rooms.”

	In 2015 alone, the EMA attracted 36,000 visitors, including scientists and health professionals, the report added.

 say the European Commission will assess bids on a series of strict criteria, including airport access and local schools, according to the 

 report. Spanish health minister Dolors Montserrat set out the case for Barcelona to host the agency during a visit to Brussels in May.

	“Barcelona is ready to host the EMA now. No one is offering a better combination of location, facilities, services, and a high quality of life from both a professional and social perspective than Barcelona,” she said.

	Amsterdam was the early favorite to secure the EMA, according to a report published by 

 newspaper in August. In the Dutch application submitted to the European Commission, it said that losing the agency will prove a double blow to London when Brexit forces its move.

	“The relocation of the agency will have considerable impact, not only because it has to move its headquarters and personnel, but also because the relationship with the U.K. Medicines and Healthcare products Regulatory Agency (MHRA) will change and potential risks need to be minimized in the event of a hard Brexit,” the document stated.

	The MHRA enjoys a lucrative relationship with the EMA, for which it carries out between 20% and 30% of the vigilance and licensing work the agency is responsible for, the report noted. The Amsterdam bid says this could change after Brexit, and that the Netherlands is well-placed to provide an alternative.

	“Brexit will not only result in the relocation of EMA to another EU member state, but also very likely in a dramatic reduction, or withdrawal, of the work of the MHRA and the Veterinary Medicines Department (VMD) in the assessment of medicinal products for human and veterinary use,” the authors wrote. “The MHRA and VMD currently also provide various services to the agency, including scientific support and [small] research assignments, regulatory advice to EMA experts, and the uptake of unclaimed scientific procedures. The Dutch Medicines Evaluation Board is able to provide a similar level of service to EMA in the event of its relocation to the Netherlands.”

, a spokesman for the MHRA said it did not necessarily believe the work it currently carried out would be lost post-Brexit. 

Vienna joins growing list of bidders to land Europe's drug regulator; Amsterdam the early favorite?

Europe’s Battle to Host EMA Post-Brexit Intensifies

	Ergomed has unveiled a plan to acquire PSR Group BV, the specialist orphan drug CRO, for a sum of up to €5.7 million (around $6.7 million).

	PSR was established in 1998 and is based in the Netherlands, and has extensive experience in rare diseases. These severe, debilitating or even life-threatening conditions affect fewer than 1 in 2000 people (European Union definition) or fewer than 200,000 people in the U.S., according to a statement from Ergomed. Around 30 million people worldwide suffer from rare diseases, and the orphan drug market to target these diseases continues to grow and requires specialist providers due to the regulatory, logistical, and operational complexities of conducting clinical trials, it continued.

	As part of the deal, Ergomed said it will continue to grow PSR’s global orphan drug development business under the PSR brand and will remain focused on its two divisions: PSR Orphan Experts, which helps biotech and pharma companies with their regulatory and clinical development of orphan drugs (about 75% of total revenue); and PSR Pharma Resource, which provides specialist trained staff (about 25% of revenue).

	The acquisition will extend Ergomed’s global coverage and increase its presence in the Middle East and North Africa, which is an important area for orphan drug development, stated the company.

Ergomed Reveals Expansion Plan in Orphan Drugs

	A new 25-page report commissioned by the 

) has highlighted the serious risks posed to public health by the relocation of the European Medicines Agency (EMA). The relocation will restrict the agency’s ability to call on and manage the network of expertise it relies on and limit staff retention and capacity, warns the authors.

	Compiled by the consulting firm Charles Rivers Associates, the study analyzes the range of activities undertaken by the EMA and considers the impact of the move on continuity, patients, and approval of new medicines.

	The report identifies two key areas-the evaluation of applications for marketing authorization and monitoring the safety of medicines across their lifecycle-as having the most significant detrimental effect on public health due to the relocation.

	Delays in evaluating applications for marketing authorization mean delays in access to new medicines for patients across Europe, while disruption to critical safety functions can lead to delays in identification, management, and communication of safety issues, thereby putting patients at risk, according to the authors.

	Transitional arrangements must be put in place to ensure the EMA has the time to manage the relocation and safeguard public health, they stated.

	"The EMA plays a key role in Europe's health, ensuring that medicines are safe, effective, and of high quality,” noted EFPIA Director General Nathalie Moll. “This report underlines the importance of both the location decision and transitional arrangements to the agency's future. Supporting the continuity of its critical functions, its ability to retain staff, and access expert networks is central to its future and to public health."