Archive

Uncategorized

By Márcio Barra

Over the years, I have created a multitude of documents to help me in my projects. I have thus decided to create a useful documents tab to go along with my articles on medicines tab, which is by far the most popular tab of Pharmupdates.

To quick start the tab, I have published both a Word template and an Endnote Style for anyone looking to submit articles to the British Medical Journal (BMJ). I will be updating the tab with new documents that I feel would be useful to someone.

British Medical Journal (BMJ) journal template and Endnote style

I created both a Word template which I used for the submission that has all the required fields for a Research Article (this includes systematic reviews as per the journal rules). I also created an Endnote style, since the link that the journal provides is broken, and the one provided in the Thomsom Reuters website is incomplete.

If you require assistance with the submission procedure (formatting, image creation, referencing) contact me.

For the BMJ Endnote style and template, send me an e-mail.

By Márcio Barra

Biotrial-laborator_3550276b.jpg

Six people were hospitalized in the Hospital of Rennes, France in serious condition, and one is brain dead, following a Phase I first-in-man clinical trial with a new drug  from the Portuguese pharmaceutical company BIAL.  The clinical trial was being conducted by French company Biotrial.

The French Health Minister, Marisol Touraine said on Friday that it is a “serious accident”. The minister added that the accident happened on Thursday and that the trial was suspended, with all previous volunteers called to undergo tests.

There are several reports online describing the drug as an analgesic product based on cannabis, but little to new additional details are being reported. Looking at BIAL´s R&D pipeline, the agent appears to be BIAL´s BIA 10-2474. BIA 10-2474 is described as a new small molecule drug that acts on the Central Nervous System as a painkiller, and currently undergoing Phase I trials.

pipeline_EN_09112015

Reports state that a total of 8 participants were participating in the trial, with two taking placebo. A message on Biotrial´s website reads:

During a FIM study which was being conducted for a sponsor, serious adverse events related to the test drug  have occurred in some subjects at our CPU. The trial has been conducted in full compliance with the international regulations and Biotrial’s procedures were followed at every stage throughout the trial, in particular the emergency procedures for the transfer of subjects to the hospital. We are in close and regular contact with the Health Authorities and Ministry in France. The priority at Biotrial remains the safety of our subjects. We are very grateful for the support we have been receiving from our clients and partners today.

BIAL is still verifying the occurrence, since the drug has been used successfully in other subjects with no issues.

Dozens of inspectors of the Policia Judiciária(Judiciary Police – PJ) are conducting a search and seizure operation at the headquarters of the Portuguese Bial Group, in Porto, and at the pharmaceutical delegations in Lisbon. It was initially believe that the Coimbra delegations were also being investigated, but this is currently not the case.

The search warrants were issuedby the Departamento Central de Investigação e Acção Penal (Central Department of Investigation and Penal Action (DCIAP))and the investigating judge Carlos Alexandre.

This operation is due to a suspected corruption case involving senior executives of the Bial Group, sales representatives, and hundreds of physicians allegedly paid to participate in scientific studies and to prescribe medicinal products marketed by the Portuguese company.  These include bonuses paid to doctors for false prescriptions of drugs that benefited from a high reimbursement rate from the National Health Service, some of which reimbursed at 100%.

The operation currently only counts with search warrants, with no arrest warrants issued thus far, but according to the Público Newspaper, later today defendants might be named in this case.

The process is centered on signs of, among other crimes, active and passive corruption for lawful and unlawful action, aggravated fraud, and document falsification.

Bial´s drug portfolio includes a number of generics, from Diazepam, Acid Folic products and Rivestigmine, to the first original drug molecule developed in Portugal, Eslicarbazepine acetate (marketed as Zebinix in Europe and as Aptiom in the US), for the treatment of epilepsy, and the upcoming Opicapone, a COMT inhibitor for Parkinsons´s Disease.

We will update the website as the news progresses.

July 6, 2015 | By Márcio Barra

Many hospitals in Portugal lack adequate support services for Clinical Trials. (Image source: Roche.pt)

All Portuguese hospitals will have to create a Research, Clinical Epidemiology and Public Health service until June 2016, and bigger hospitals will have to do so until the end of 2015, according to Order (extract) No 7216/2015, published on July 1st on the Diário da República website.

This requirement comes from the fact that the majority of hospitals and health centers in Portugal do not have oriented services to support these kinds of research activities, such as clinical trials, observational trials, and epidemiological studies . These new units are an attempt to fill this gap, and as such, the responsibilities of the Research, Clinical Epidemiology and Public Health services will include:

  • Collaborate in the provision of hospital care and activities that promote general health in the population, including planning, monitoring and evaluation of health care and organization of health services
  • Support and promote the participation of the hospital in which they are inserted in public health programs
  • Support for epidemiological, clinical, public health and health care research activities, by providing research enterprises for health professionals, training in research methodology, promote good research practices, and providing human and logistical capacity for research activities
  • Promote hospital collaboration in research projects led by third parties and participation in research networks
  • Prepare hospitals for emergencies, such as epidemics, disasters or other threats to public health
  • Support or ensure the planning, creation, development and management of hospital records, national health registries, and data relating to the literacy of health professionals regarding computer systems and statistics
  • Propose, manage and collaborate on intervention programs for disease prevention and health protection

Moreover, a Research, Clinical Epidemiology and Public Health service will be able to include many different professional groups (physicians with experience in clinical research, nurses, and biostatisticians, among others. No mention of clinical research coordinators), which may, with the permission of the hospital board, accumulate functions with other services.  The Diário de Notícias is reporting that physicians will be able to devote 75% of their time to research activities, and that there will be incentives for physicians who purse research, such as salaries increase or career progression.

Research, Clinical Epidemiology and Public Health services should must become operational by December 31, 2015, in Hospitals, Medical Centers or Local Health Units of Groups III and IV, according to Decree No. 82/2014 of April 10. These include:

  • Centro Hospitalar e Universitário de Coimbra, EPE
  • Centro Hospitalar de Lisboa Central, EPE .
  • Centro Hospitalar Lisboa Norte, EPE
  • Centro Hospitalar de São João, EPE
  • Centro Hospitalar Porto, EPE .
  • Instituto Português de Oncologia de Coimbra, Francisco Gentil, EPE
  • Instituto Português de Oncologia de Lisboa, Francisco Gentil, EPE
  • Instituto Português de Oncologia do Porto, Francisco Gentil, EPE
  • Centro de Medicina Física de Reabilitação do Sul
  • Centro de Medicina de Reabilitação da Região Centro – Rovisco Pais
  • Centro de Reabilitação do Norte
  • Centro Hospitalar Psiquiátrico de Lisboa
  • Hospital Magalhães de Lemos, EPE

All remaining Hospitals, Medical Centers or Local Health Units have until June 30, 2016 to implement this service.

MS fight

June 30, 2015 | By Márcio Barra

Genentech, a member of the Roche Group, announced today that its Multiple Sclerosis (MS) agent Ocrelizumab, for people with relapsing multiple sclerosis, met its main endpoints in two final-stage Phase III clinical trials (the OPERA I  and OPERA II  studies)

Ocrelizumab is a humanized anti-CD20 monoclonal antibody that acts as a suppressor of CD20-positive B cells, a type of cell thought to be behind myelin destruction in MS. Other monoclonal antibody treatments for MS include Daclizumab (currently in clinical trial phase) and Alemtuzumab (commercialized as Lemtrada).

The OPERA I and OPERA II phase III studies recruited a total of 1656 participants with relapsing remitting MS who took either ocrelizumab 600mg every 6 months or interferon beta 1a (Rebif, an injectable MS treatment marketed by Merck Serono) three times per week for approximately two years. Both studies shared the same set of endpoints. Primary endpoint was annualized protocol-defined relapse rate (ARR) at two years (96 weeks). Secondary endpoints included time to onset of confirmed disability progression, and safety related endpoints such as the total number of T1 Gadolinium-enhancing lesions, and total number of new and/or enlarging T2 hyperintense lesions as detected by brain MRI.

In the press release, Roche stated that ocrelizumab “significantly reduced” relapses, alongside a reduction of disability progression compared with Rebif, as measured by the Expanded Disability Status Scale (EDSS), the standard MS evaluation tool.

Regarding the safety endpoints, Roche stated the drug showed a similar number of adverse effects as Rebif, the most common being infusion-related reactions involving the immune system. Ocrelizumab infusion also led to a significant reduction in the number of lesions in the brain compared with Rebif, as observed by MRI scans.

However, no “real” results were shared by Roche, as the company declared that further analyses of the OPERA studies are ongoing, and detailed data will be presented at an upcoming medical congress. Roche is also preparing to start filling for regulatory approval in 2016, according to Sandra Horning, M.D., chief medical officer and head of Global Product Development:

“Ocrelizumab showed remarkable improvements over a standard-of-care medicine across clinical and imaging endpoints in two pivotal studies. Ocrelizumab has the potential to make a meaningful difference for people with MS, a chronic and debilitating disease. Based on these compelling results, we plan to submit the data for review to U.S. and EU regulatory authorities in the first quarter of 2016.”

Alongside the OPERA studies, Ocrelizumab is also being studied in a currently ongoing Phase III clinical study entitled ORATORIO, a placebo-controlled study in people with Primary Progressive Multiple Sclerosis.

November 19, 2014 | By Márcio Barra

flag

The newly release Ordinance No. 231-A / 2014 of November 12 just issued the new benchmark countries for 2015 to calculate drug prices in Portugal. The upcoming drug pricing revision will be made by referencing the values practiced in Slovenia, Spain and France. Last year1s reference countries were Spain, France and Slovakia. This revision will affect the prices of all non-generic drugs and drugs that will be launched in 2015. The ordinance also states that the price of generic drugs will not increase in 2015.

This is the third change since the implementation of the rotating reference pricing system, as decreed by Decree-Law No. 112/2011, of November 29, and the enactment of the Memorandum of Understanding between Portugal and Troika in 2011.

Up until 2011, the reference countries were France, Spain, Italy and Greece.  In 2013, they were Spain, Slovenia and Italy, and in 2014, Spain, France and Slovakia were the 3 chosen by the Portuguese Ministry of Health.

Source

November 18, 2014 | By Márcio Barra

Untitled-1

Pharmupdates is back! After a hiatus, I felt the time was right to resume updating once again, this time with an emphasis on the Portuguese side of news. So, enjoy the first article, part 1 of a new series detailing the new clinical research Law in Portugal, Law 21/2014. Please be mindful of typos, as the bulk of my writing is now done in a foreign keyboard.

_______________________________________________________________________________________________________________

Up until April 2014, the procedure for submitting and requesting an approval of a clinical trial in Portugal was governed by Law 46/2004 of 19 August 2004. This law was revoked by Law 21/2014, of 16 April 2014, which introduced some new considerations that sponsors have to be aware when seeking to conduct clinical trials in Portugal. Both laws incorporate the principles of the Clinical Trials Directive 2001/20/EC. It is worth noting that while Law 21/2014 introduced new procedures for submitting a clinical trial authorization request, some of the procedures are still not fully operational. Thus, some of the principles of previous law are still in use.

Concerning the approval of a clinical trial, according to law 21/2014, like the law before it, an approval request has to be sent to the Portuguese National Competent authority (INFARMED), under Article 26. º for clinical trials with experimental drugs. The new law has some changes on the way each chapter is organized. While in the previous law, the entire range of available procedure is detailed in chapter III and IV, in the new law, the content is more spread out, making for a more complex read.

Under the new law, the sponsor is to request permission to INFARMED through the RNEC (RNEC – National Clinical Trials Registry). Within 30 business days, the governing board of the INFARMED has to issue an opinion. However, the RNEC is still not in operations as of this moment, and so the submission procedure is still conducted under Law 46/2004. The same holds true under law 21/2014 for CEIC’s (the Portuguese National Ethics Committee for Clinical Research) approval procedure, with the sponsor having to request an opinion through the RNEC. The CEIC, or a designated CES (local Committees for Health Sciences), then has 30 business days to issue their opinion on the ethical aspects of the trial. However, this period can be extended for 20 days if the intervention in question is a genetic therapy, a somatic cell therapy, or an intervention that contains genetically modified organisms. If the CEIC or CES has to resort to outside expert opinion, the timeline can be extended for an additional 50 days. Xenogeneic therapies have no set deadline for a statement to be issued. INFARMED enjoys the same extended time frames for the same special cases. As for the National Committee for Data Protection, the committee has a 30 day timeline to issue a statement.

The CEIC is still to publish more in-depth guidance for submission of a clinical trial authorization request under law 21/2014. According to the Law 46/2004 and the guidance published by CEIC, the approval request has to comply with Annex I of CEIC’s guidance note (found here: http://goo.gl/w5fz08 ).

A more in-depth look will be now provided at each article of the now governing law, highlighting the differences between the previous version.

A noticeable difference compared to the previous law of clinical trials is that the new law applies to all clinical research conducted in humans. This includes observational studies, which are now too encompassed in Law 21/2014, and studies which use individual health data (such as registries).

The new law further emphasizes the importance that is to be given to the clinical trial participant. Article 3 introduces a new statement, highlighting that “in clinical studies, all precautions must be taken to respect the privacy of the individual and minimize any damage to their rights of personality and their physical and mental integrity.”

Article 4, on the evaluation of risk/benefit by the national competent authority, now includes a short statement, declaring that the experimental therapy risk/benefit can be reviewed at any time during the trial, if new evidence appears or through interim analyses of the study itself. This highlights the growing trend in clinical trial design of adopting interim analysis in their statistical analysis plan.

Article 6, which deals with the topic of financial compensation of patients in clinical trials, introduces some new points. Patients are not to be granted any financial incentives or benefits, save for expenses reimbursement expenses and compensation for damage suffered from clinical trial participation. Some minimum requirements for the protection of participants are also more fleshed out and detailed in comparison to the previous law. The assigned ethic committee (either the CEIC or a CES) is also provided with the authority to, in non-interventional studies and exceptional situations, remove the need for explaining to the participant what the trial is about and attaining informed consent.

Specific provisions are established for clinical trial participants, including the minimum requirements for the protection of participants, specific provisions regarding the participation of minors and disabled individuals in clinical trials, as well as provisions related to obtaining informed consent (Articles 6 to 8).

The procedure for attaining consent on minors too has been more detailed. Alongside the other requirements, a clinical trial can only be performed on minors when it has been obtained the informed consent of a minor aged above 16 years and his legal representative. If the minor has less than 16 years, the representative is the sole responsible for grating informed consent, although it must reflect the presumed will of the minor. The assigned ethic committee again is given the right, under exceptional circumstances, to waive the requirements of informed consent and informing the minor patients in clinical studies without intervention. The assigned ethic committee is given the same right for participants of age unable to provide informed consent.

Part 2 is coming next

Sources:

Lei n.º 21/2014, de 16 de abril