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Navigating the Medical Malpractice Minefield – Strategies for Success


For this featured interview, based on his experience of more than 3000 cases of medical malpractice, we asked Rodney “What have been the most common difficulties experienced by the legal profession when it comes to running cases of medical negligence/malpractice and how can these be overcome?”

Rodney identified ten themes he has noted over the years, which can catch out even the most experienced lawyers and he went on to discuss each in turn.


As defence organisations point out, only one in five complaints about possible medical negligence have a likelihood of success and this has been borne out in his own practical experience. It is, therefore, necessary to triage or screen cases at the outset, to make sure that they at least have the potential for being able to display the essential triad of duty of care, breach of that duty, and consequential, or but for, damage. Some cases may appear obvious on face value but as most lawyers have limited medical knowledge, it is important to obtain a preliminary screening report by a medical expert to identify exactly who had the duty of care, what standard should be applied, and whether or not any damage is likely to have occurred specifically because of any suggested breach. This initial opinion can usually be based on a detailed statement from the client but may require the perusal of specific notes and records.

In many cases, the client’s concerns are in fact more in the nature of a complaint about behavioural issues, including the attitude of staff, poor communication skills, or delays in managing their case. These are not within the legal definition of medical negligence or malpractice and are more appropriately handled through the normal complaints procedure for the practice or institution involved, rarely proceeding to litigation. Such complaints usually produce a written response within a matter of months.

 On occasions, a hospital or other source may have instigated Serious Incident Review which may identify areas where medical care has been deemed sub-standard and could be subject to a legal challenge. However, if lawyers become involved before such reviews are carried out, it is likely the report would not be released to the client as the matter would be deemed sub-judice.

A secondary review may also be appropriate once the medical evidence is complete. This considers all available evidence and allows the medical expert to work with counsel/ trial lawyers to consider the implications of potential strengths and weaknesses in the case before court proceedings.

Screening helps to contain costs by providing an early general overview of a case, for a fraction of the fees which would be required for a full liability and causation report plus a condition and prognosis report. Too often, Rodney says, he has noted lawyers skipping this vital preliminary phase and proceeding to obtain full reports which require considerable time, effort and for which costs which may not be recoverable.

Finally, he points out that the word ‘SCREENING’ is an excellent acronym for the other nine areas where difficulties can and do arise.


Almost all jurisdictions have a statute that limits the time allowed for the initiation of a case, usually to between one and five years. This is based on the date the cause of action accrued, modified by circumstances such as the time when the client is judged to have had reasonable knowledge of what has happened, related to age, for instance allowing young persons to bring cases from childhood after their age of emancipation and sometimes for those with mental health issues. Allowing the use of such a statute in defence of a claim is normally within the discretionary power of the court. Therefore, it is important to make sure there is no time bar or, in the alternative, there is a reasonable chance a court will allow proceedings to continue.

The presence of such a statute also serves as a warning to lawyers they should avoid any unnecessary delay in moving forward with their investigations or they may unintentionally run out of time and find themselves on the receiving end of a claim in professional negligence. This is another benefit from swift, initial screening which allows a determination to be made whether or not matters are likely to progress, issuing a holding writ if necessary. If not, the client can be informed, allowing them the latitude to seek other medical or legal advice should they wish before they run out of time.


Counsel/Trial Lawyers should be consulted early after the initial screening. As well as giving legal direction for the proceedings, receipt of the screening report allows a more informed discussion of the case, particularly in the raising of particular questions they wish to be included in the briefing of experts. Counsel should maintain an ongoing overview as the various reports are received, to ensure the case stays on track and giving advice on handling any new issues as they arise.


The initial screening report should give advice on which specialties should be involved and in what order reports should be obtained. Under normal circumstances, the initial report is likely to deal with liability and causation. However, occasionally it is more appropriate to have a report detailing the likely consequential damages which may have arisen as, if these cannot be determined, a report on liability and causation is likely to be superfluous. A subsequence is not the same as consequence and just because a client has a particular complaint does not mean that it is in any way related to a breach of the duty of care. As an example, some weakness in a wrist following a well-healed fracture of the scaphoid bone is more a consequence of the injury even if it could be established the fracture was not fully stabilised for a week after the incident. Many cases fail on causation and, unless this is clear, there is no point in obtaining expert reports to deal with the nature of the injury, the present condition, or likely prognosis.

A duty of care is usually easy to determine. However, sometimes it is not so obvious and a case in medical negligence may be considered against a particular Consultant or Attending when a closer examination would reveal it is actually in the remit of other professionals from different medical specialities or, indeed, para-medical specialities such as nursing or physiotherapy. It is important therefore reports identify and focus on the key issues in the case and clearly elucidates if more than one speciality group has potentially breached their duty of care, such as a General Practitioner, Accident, and Emergency doctor, or other staff, all of whom may need to be co-joined.


Eminence is not the same as expertise and just because someone is well-known in their profession or has appeared in other cases,  does not mean they are appropriate for the subject under discussion. Further, they may not have expertise in writing medical-legal reports, having meetings to negotiate with other experts, or giving evidence in court.

 Experts must be chosen wisely, clearly understand their primary duty is to the court no matter who instructs them, and be a recognised expert in the subject matter of the case. They must be able to reason logically, both orally and on paper without using hyperbole, in a way which laypersons in general, and the court in particular, can understand and interpret. They need to be coldly objective and demonstrate no conflict of interest or bias on behalf of the plaintiff, the defence, or a specific line of medical therapy. It is quite reasonable for an expert to advocate a particular view as to how they feel a  case should be managed, however, they must also be prepared to accept the fact that there is liable to be a reasonably held range of opinion which they should also state and, if necessary, indicate by logical argument why their opinion should be given preference.

 Finally, experts have to accept that the standard is reasonableness, not perfection, and be prepared to alter their stated opinion if new evidence, which they have not previously considered, is presented during proceedings.

Expectations of the client

In some case, especially when the consequences have been devastating for the plaintiff, even the most experienced lawyers may become emotionally involved. The rule is empathy, not sympathy and to remain objective throughout so clear, unencumbered, professional advice may be given to the client. At an early stage, it is necessary to have an in-depth conversation with the client in order to ascertain exactly what outcome they expect from the case. Some want to punish, others wish for monetary compensation but on many occasions the client is primarily looking for a detailed, understandable explanation as to what happened. Anger is a common emotion that is best handled through empathy, understanding, and certainty they are being listened to, rather than any logical argument. Managing a client’s expectations is therefore one of the most important functions of a lawyer and vital if the client is to feel content with the outcome, however long the process takes.

Notes and records

Guided by the initial screening and comments of Counsel, all appropriate notes and records need to be expeditiously sourced, ordered, and paginated for ease of reference especially as, in some cases, many thousands of pages may be involved.  As well as contemporaneous medical notes, other records may be valuable, for instance, letters to the client from an institution following a complaint or other internal documents such as a report resulting from a serious incident review. External documents may be available following a post-mortem or inquest and the client themselves may have notes in a diary or even photographs on their phone.

Medical experts should be suspicious if they find notes have been redacted, especially if this has been carried out by the legal team either for the defence or the plaintiff. Unless the redaction relates to the names of third parties, it is not best practice to edit the notes in any way before forwarding them to an expert.


Medical-legal cases can be very expensive and costs need to be controlled. There is no such this as a water-tight case and loss can result in a heavy financial burden. Any law firm should be clear about how they are going to be compensated in the event a case does not proceed. Unfortunately, not doing so has led to a number of cases being pursued long after they should have been discontinued, taking proceedings up to the door of the court in order to try and get a settlement of some sort to at least cover expenses. This sort of behaviour is frowned upon by the court system and is bordering on unethical.

Some form of insurance is therefore valuable and in some cases, the client can self-insure or have a legal policy in place to at least cover initial advices. It may also be possible to obtain After the Event Insurance if it is clear from the initial reports and the opinion of Counsel the case has a high likelihood of success. Using a blunderbuss approach, ordering multiple expert reports at an early stage, and even obtaining second reports when one expert report does not appear to back the client’s case is a recipe for financial disaster. Once again, a process or system for conducting medico-legal cases is vital to success, remembering that a  “system” is there to Save, Yourself, Stress, Time, Energy, and Money.

No medical knowledge/experience

Rodney points out his credo is “to help clients, their legal advisors and the courts to understand more clearly the nature of medical evidence in individual cases so they can make better decisions.” This should be a fundamental belief for all of those preparing expert reports. Courts make determinations, experts assist by rendering the medical evidence understandable for a lay audience and by giving advice as to acceptable standards of care.

The lawyers most likely to get into trouble with the process are those who do not undertake these proceedings on a regular basis. There are many nuances from both a medical and legal point of view that can make cases that look similar produce markedly different outcomes. One of those is an understanding that perfection is not a reasonable standard and secondly that no medical treatment can be guaranteed success. Known complications arise which is the purpose of the doctrine of informed consent. However, it is also true, that just because a patient has been told about the potential risks associated with a particular therapy or procedure, does not mean that when such difficulties arise it could not be considered due to a negligent act. It very much depends on context and circumstances in the individual case and again the expert should be in the best position to determine whether a poor outcome would reasonably be regarded as due to a known complication in all the circumstances or represent a negligent breach of the duty of care.

 In circumstances where experts differ in the interpretation of an objective finding, it is for the courts to assess all the evidence before them and make a determination. Sometimes this is difficult for lawyers to understand and particularly if they lack medical knowledge and experience of such cases. Especially at an early stage in their career, it is good practice to have coaches and mentors both within and outside their firm or even the profession. By reflecting on more challenging cases, they can continue to get the learning from them which in turn grows their expertise in what is a niche area and helps to professionalise their practice.

Guiding/directing an expert

It is an expert’s duty to remain independent and objective, no matter who engages them. It is certainly reasonable to ask questions as to why they have come to a particular conclusion or to ask for an evaluation of new evidence, but it is not acceptable to ask an expert to ‘tweak’ a report in order to place a client in a better light.  While some lawyers attempt to justify this by stating they are only trying to do their best for the client, they do not serve either the justice system or their profession well.  An expert who agrees to change any element of a report under such circumstances is compromised, not just for that case but for any other, and is open to being severely criticised in court. It is not unknown for experts found to have breached this code of conduct to have their professional registration to practice removed by their governing body. Such censure can have considerable implications for their personal, professional, and financial well-being.


In reflecting on the most frequent challenges he has come across in his three decades of dealing with personal injury and medical malpractice cases, Rodney concludes that representing clients in cases of potential medical negligence requires legal representatives to have an understanding of the many complexities involved and to be aware of the pitfalls. Securing early and proficient advice from an appropriate medical expert can mitigate the financial and reputational risks.

It is clear why Rodney is regarded as one of the foremost authorities on the medical aspects of medico-legal practice, and why his keynote speaking, coaching, and tutoring is so highly regarded by lawyers and doctors involved in such cases.

How to ensure non-NHS health care organisations are prepared for CQC registration

Registering with the Care Quality Commission (CQC) is compulsory for all providers of health and social care in England, not just those as part of the NHS, and it is against the law not to do so. The provider can be an individual, a partnership or an organisation and knowing which of these legal entities applies is important. The CQC’s aims are to set standards, ensuring that they are met and, where possible, improved upon. With a growing number of non-health care organisations, these standards exist in order to protect users and improve their experiences of health and social care.

Providers should be prepared to register by understanding what is involved in the application process, what information should be given and how much it costs. Here are a few pointers to give providers an idea of how to get ready for registration.

Getting the right checks
Applying for a CQC-countersigned DBS check is the first absolute must when it comes to preparing. This covers individuals who carry on or manage a care service, all partners, and registered managers. To avoid common mistakes that will hinder registration, visit the CQC website.

Stating the purpose
Providers should be in a position to describe what they do, where they do it and who they do it for so that they can write this in their statement of purpose. This statement also includes some of the details listed below.

Understanding ‘regulated activities’
Organisations need to be aware of the 14 health care services that are regulated by the CQC and then consider which of these ‘regulated activities’ they will continue with.

Having a registered manager
Alongside this, at least one registered manager must be in place to manage the regulated activities. This person must work routinely in the activities and have some legal responsibility in relation to their position. The new registered manager should apply at the same time as the new provider.

Who can be contacted
It is important that the organisation has a nominated individual who can be contacted about the regulated activities and has some supervision responsibilities for these. It is advised that this person is not the registered manager if it can be avoided.

Where the activities take place
A regulated activity might be carried out as one service but at many locations. In this case, the locations must be clearly stated as this is a declaration about compliance with the relevant activity standards at each location.

Supporting the application
Providers need to know how to get hold of policies that can support their application, such as those on Management, Safeguarding and Governance. There will also need to be some evidence of the registered manager’s position.

Providing references
Individual providers need to supply details of employment history and medical fitness, whilst
partnerships need to supply the same information for all partners. However, organisations do not need to supply this information for their nominated individual.

Covering the fees
Applicants need to be aware of the fees involved as this will need to be paid on the same date each year. The fee amount depends on the type of provider and how many people benefit from the service.

Applications for registration are made online via the CQC website, where there are also a number of guidance documents to help with registration.

Registering with the CQC may seem like a lengthy and cumbersome procedure. However, it is worth bearing in mind that they are looking for ‘fitness’ and compliance with the relevant regulations, and if applicants are found to be non-compliant they will have their application refused. There are many conditions that the CQC needs to consider so it is worth taking the time to prepare and get registration right first time.

The EU General Court Endorses the Reasoning of the European Commission in Relation to Reverse Payment Settlements

With the Lundbeck Decision, the European Commission’s (the “Commission” and the “Decision,” respectively) ended its ten-year investigation on reverse payment settlements and found that the Danish pharmaceutical company, Lundbeck, and four generics producers had concluded anticompetitive agreements, in breach of Article 101 of the Treaty on the Functioning of the European Union (the “TFEU”).[2]  According to the Commission, this would have allowed Lundbeck to keep the price of its drug citalopram artificially high.

On 8 September 2016, the EU General Court (the “General Court”) confirmed that certain pharmaceutical “reverse payment settlements” can constitute a breach of the EU antitrust rules (the “Ruling”).[3]  Under the so-called “reverse payment settlement agreements”, an original pharmaceutical manufacturer, or “originator”, settles an IP challenge from a manufacturer of generics by paying the latter to stay out of the market.

II. Background

According to its website, Lundbeck is “ a global pharmaceutical company specializing in psychiatric and neurological disorders”.[4]  These include medicinal products for treating depression .[5]  From the late 1970s, Lundbeck developed and patented an antidepressant medicinal product containing the active ingredient ‘citalopram’.[6]

After its basic patent for the citalopram molecule had expired, Lundbeck only held a number of the so-called “process” patents, which, according to the Commission, provided only “a more limited protection”.[7]  In particular, Lundbeck had filed a salt crystallisation process patent.[8]

According to the Commission, in 2002, Lundbeck concluded six agreements concerning citalopram with four entities active in the production or sale of generic medicinal products, namely Generics (UK), Alpharma, Arrow and Ranbaxy.  Always according to the Commission, in return for the generic undertakings’ commitment not to enter the citalopram market, Lundbeck paid them substantial amounts .[9]  In addition, Lundbeck purchased stocks of generic products for the sole purpose of destroying them, and offered guaranteed profits in a distribution agreement.[10]

In October 2003, the Commission was informed of the existence of the agreements at issue by the Konkurrence- og Forbrugerstyrelsen (the “KFST”, the Danish authority for competition and consumers).[11]  The Commission took over the case and, by decision of 19 June 2013, made the following findings:  (i) Lundbeck and the generic undertakings were at least potential competitors;[12] and (ii) the agreements at issue constituted restrictions of competition by object, in breach of the prohibition of anticompetitive agreements provided for under Article 101 TFEU.[13]  The Commission imposed a total fine of €93.7 million on Lundbeck and € 52.2 million on the generic undertakings.  The Commission took into consideration the length of its investigation (almost ten years) as a mitigating circumstance which led to fine reductions of 10%.[14]  Lundbeck and the generic undertakings brought actions before the General Court, seeking the annulment of the Commission’s decision.  The Court dismissed the actions brought by Lundbeck and the generic undertakings and confirmed the fines imposed on them by the Commission.[15]

After the Lundbeck case, in 2013 and 2014, the Commission imposed fines on companies in two other reverse settlement investigations – one concerning fentanyl, a pain-killer[16], and the other concerning perindopril, a cardiovascular medicine.[17]  The Fentanyl decision was not appealed.  Several appeals against the Servier decision are pending before the General Court.[18]  In 2016 in the Paroxetine Investigation, the UK Competition and Market Authority issued infringement decisions to a number of companies regarding ‘pay-for-delay’ agreements over the supply of an antidepressant.[19]

In addition, since 2009, the Commission has been continuously monitoring patent settlements in order to identify settlements which it regards as “potentially problematic” from an antitrust perspective, namely those that limit generic entry against a value transfer from an originator to a generic company.  The latest report was published in December 2015.[20]

III. The Ruling

First, like the Commission, the Court analysed whether Lundbeck and the generic manufacturers concerned were indeed potential competitors at the time the agreements at issue were concluded.[21]  The General Court made the following findings in this regard:

In order for an agreement to restrict potential competition, it must be established that, had agreement not been concluded, the competitors would have had “real concrete possibilities” of entering that market.[22]  The Court held that the Commission had carried out a careful examination, as regards each of the generic undertakings concerned, of the real concrete possibilities they had of entering the market.  In doing so, the Commission relied on evidence such as the investments already made and the steps taken in order to obtain a marketing authorisation[23]

Moreover, the Court noted that in general the generic undertakings had several real concrete possibilities of entering the market at the time the agreements at issue were concluded.[24]  Those possible routes included, inter alia, launching the generic product with the possibility of having to face infringement proceedings brought by Lundbeck (i.e., the so-called launching ‘at risk’).[25]  More precisely, the General Court was of the view that “the presumption of validity cannot be equated with a presumption of illegality of generic products validly placed on the market which the patent holder deems to be infringing the patent”.[26]  Consequently, the Court, continued, “’at risk’ entry is not unlawful in itself”.[27]

As rightly noted by commentators, these considerations introduce a further layer of complexity in the already intricate relationship between EU Competition law and IP law. In addition, since the right to exclude lies at the core of any IP right, it can be argued that the Commission’s findings infringes Article 345 TFEU, according to which “[t]he Treaties shall not prejudice the rules in the Member States governing the system of property ownership”.  Thus, Ibañez Colomo has noted that “Lundbeck departs from the principle whereby an agreement is not restrictive by object where it remains within the substantive scope of an intellectual property right”.[28]  This principle would derive from the Eraw-Jacquery,[29] Coditel II,[30] BAT v. Commission and Nungesser[31] rulings of the ECJ.  Ibañez Colomo’s point becomes particularly clear at para. 335 of the (Lundbeck) Ruling where the General Court expressly noted that “even if the restrictions set out in the agreements at issue fall within the scope of the Lundbeck patents – that is to say that the agreements prevented only the market entry of generic citalopram deemed to potentially infringe those patents by the parties to the agreements and not that of every type of generic citalopram – they would nonetheless constitute restrictions on competition ‘by object’ since, inter alia, they prevented or rendered pointless any type of challenge to Lundbeck’s patents before the national courts, whereas, according to the Commission, that type of challenge is part of normal competition in relation to patents (recitals 603 to 605, 625, 641 and 674)”.[32]

Second, the Court analysed whether the Commission was entitled to conclude that the agreements at issue constituted a restriction of competition by object, a point to which we will turn next.

IV. Conclusions:  On Reverse Payments as Restrictions of Competition by Object

The Lundbeck ruling brings a number of what Donald Rumsfeld would probably refer to as “known unknowns”, that is things we know we do not know, in relation to reverse payment settlements.[33]  Indeed, the findings of the Lundbeck ruling can be summarised as follows:

  1. There are certain patent settlements which are likely to be considered compatible with Article 101 TFEU. This is the case of settlements:

    a. In which, in the words of the General Court, “(i) payment is linked to the strength of the patent, as perceived by each of the parties; (ii) [payment] is necessary in order to find an acceptable and acceptable and legitimate solution in the eyes of two parties and (iii) [payment] is not accompanied by restrictions intended to delay the market entry of generic”.[34]

    The inclusion of the word “and” is worrying.  The requirements set out in the preceding paragraph should be alternative and not cumulative.  Otherwise for a settlement to be lawful it must not delay entry (which probably is enough, in and of itself, to avoid the antitrust concern, namely, a delayed entry of generics) and it must be necessary (i.e., it probably needs to meet the requirements of an ancillary restraints defence, more on which below) and the payment might be linked to the strength of the patent “as perceived by each of the parties”.  Such an intrinsically subjective requirement appears to the writer as particularly complicated to administrate and at odds with the objective nature of Article 101(1) TFEU.  It would appear that the Court is encouraging conversations such as the following: “let’s settle, but only if we can ensure the settlement reflects (and comes across as reflecting) your and my perception of the strength of the patent (and a number of other cumulative requirements my lawyers and I need to meet), otherwise we might have an antitrust concern”.

    b. Qualifying for an ancillary restraints defence. e., settlements in relation to which the parties to the settlement (for the burden of proof will be on them) can demonstrate they are objectively necessary and proportionate in order to defend their IP rights.[35]

  1. There are certain patent settlements which are likely to be considered incompatible with Article 101 TFEU as restrictions of competition by object. The ruling is not particularly clear in this regard.

    a. Aliteral reading of paragraph 334 of Lundbeck could potentially make “problematic” each patent settlement “where they [provide] for the exclusion from the market of one of the parties, which was at the very least a potential competitor of the other party, for a certain period, and where they were accompanied by a transfer of value from the patent holder to the generic undertaking liable to infringe that patent (‘reverse payments’).”

    b. A more holistic reading of Lundbeck would confine the Commission’s finding to the facts of the case. Even though it is difficult to pinpoint what the court considered to be the decisive factors when stating that a reserve settlement constituted a restriction by object, the following factors appear to have been relevant:

    1. The allegedly “disproportionate nature” of such payments “combined with other factors, such as the fact that the amounts of those payments seemed to correspond at least to the profit anticipated by the generic undertaking”.[36] Referring to the US Supreme Court ruling in Actavis,[37] the Court indicated that “the size of a reverse payment may constitute an indicator of the strength or weakness of a patent”.[38]  According to the Commission “the higher the originator undertaking estimates the chance of its patent being found invalid or not infringed, and the higher the damage to the originator undertaking resulting from successful generic entry, the more money it will be willing to pay the generic undertaking to avoid that risk”.[39]
    2. Indeed, the correspondence between the amount of the payment that seemed and the profit anticipated by the generic undertakings if they had entered the market.[40] According to the Commission “the value which Lundbeck transferred, took into consideration the turnover or profit the generic undertaking expected if it had successfully entered the market”. [41]
    3. The absence of provisions allowing the generic undertakings to launch their product on the market upon the expiry of the agreement without having to fear infringement actions brought by Lundbeck.[42]
    4. The presence in those agreements of restrictions going beyond the scope of Lundbeck’ s patents,[43] such as restrictions with regard to citalopram products that could have been produced in a non-infringing manner.[44]
    5. According to the Court, “the agreement at issue transformed the uncertainty in relation to the outcome of such litigation into the certainty that the generics would not enter the market which may also constitute a restriction on competition by object when such limits do not result from an assessment, by the parties of the merits of the exclusive right at issue, but rather from the size of the reverse payment which, in such case, overshadows that assessment and induces the generic undertaking not to pursue its independent efforts to enter the market”.[45] The generics thus no longer had an incentive to continue their independent efforts to enter the market[46].
  1. There are certain patent settlements which (presumably) are considered to be incompatible with Article 101 TFEU as restrictions of competition by their effects. Hic sunt dracones.  More precisely, given that none of the pay-for-delay decisions dealt with by the  Commission conducted an effects analysis, we are left without guidance as to how that analysis will be conducted.  Again, a known unknown.  The Commission’s ten-year investigation on reverse payment settlements has not shed light to how to conduct an effects analysis under Article 101(1) TFEU.  We are left, perhaps, with the findings of the US Supreme Court in Actavis, according to which, “the likelihood of a reverse payment bringing about anticompetitive effects depends upon its size, its scale in relation to the payer’s anticipated future litigation costs, its independence from other services for which it might represent payment and the lack of any other convincing justification.  The existence and degree of any anticompetitive consequences may also vary among industries”.[47]

Moreover, to the extent that the case for restrictions of competition by object is administrability, this author cannot but note that the Lundbeck ruling does not constitute a positive evolution.  The General Court noted that “it is established that certain collusive behaviour […] may be considered so likely to have negative effects, in particular on the price, quantity or quality of the goods and services, that it may be considered redundant, for the purposes of applying Article 101 TFEU to prove that they have actual effects on the market”.[48]  However, the Decision has 464 pages.  Given that the Fentanyl and Servier decisions occupy 147 and 813 pages, respectively, in investigations that lasted for almost ten years, 27 months and 5 years (again, respectively), one cannot but wonder whether the Commission’s resources would have been better spent analysing the actual effects of the agreement and not defending a legal category.

*                                              *                                              *

   [1]   Pablo Figueroa and Suzanne Nusselder are, respectively, a senior associate and a trainee with Gibson, Dunn & Crutcher LLP’s Brussels office.  In addition, Pablo Figueroa is a visiting Lecturer at Queen Mary University (London, United Kingdom), a guest lecturer at Oxford University and a guest lecturer and senior external researcher at Deusto Translaw Research Group.  The author is grateful to Fredrik Löwhagen, from Linklaters, Rais Amils, from Clifford Chance, Paulius Mencas from Valiunas Ellex and Professors Herbert Hovenkamp, Stephen Calkins and Pablo Ibañez, and to Rakhal Zamal, trainee at the Brussels office of Gibson Dunn & Crutcher LLP, for their comments.  Any remaining mistake is of the authors.  The views in this article do not represent those of Gibson, Dunn & Crutcher LLP or its clients.

   [2]   Commission Decision C(2013) 3803 of 19 June 2013 relating to a proceeding under Article 101 [TFEU] and Article 53 of the EEA Agreement, Case AT.39226 — Lundbeck (the “Decision”).

   [3]   See T-472/13 Lundbeck v. Commission [NYR] (the “Ruling”).

   [4]   See, for more detail,

   [5]   See Ruling, at para. 1.

   [6]   See Ruling, at para. 16.

   [7]   See European Commission Press Release IP/13/563, 19 June 2013, available at  It should be recalled, in this regard, that, according to Article 27 of the TRIPS (WTO) Agreement, “patents shall be available for any inventions, whether products or processes, in all fields of technology, provided that they are new, involve an inventive step and are capable of industrial application“.

   [8]   See Ruling, at para. 20.

   [9]   See Ruling, at paras. 26; 35; 39; 42-43 and 47-48.

  [10]   See Ruling, at para. 26; 35; 39; 42-43; 47-48.

  [11]   See Danish Competition and Consumer Authority Press Release 1120-0289-0039/VIS/SEK, 28 January 2004 , available at: (Only available in Danish)

  [12]   See Decision at paras. 610 ff.

  [13]   See Decision at paras. 647 ff.

  [14]   See Decision, at paras. 1306, 1349 and 1380.

  [15]   See Ruling, Operative part.

  [16]   See European Commission Press Release IP/13/1233, 10 December 2013, available at:

  [17]   See European Commission Press Release IP/14/799, 9 July 2014, available at:

  [18]   See OJ L C-462/25, 22.12.2014

  [19]   See Case CE/9531-11 Paroxetine 12 February 2016.  For a comment on the case see Ezrachi, A., EU Competition Law: An Analytical Guide to the Leading Cases, 5th Edition, Bloomsbury, 2016, 396

  [20]   See, European Commission, “6th Report on the Monitoring of Patent Settlements (period: January-December 2014)”, 2 December 2015, available at

  [21]   See Ruling.  The General Court separately analysed each agreement.  See, inter alia, in relation to Lundbeck and Merck, para. 225; in relation to Lundbeck and Arrow, paras. 266-270, in relation to Lundbeck and Alpharma, para. 290 and, in relation to Lundbeck and Ranbaxy, para. 330.

  [22]   See Ruling, at para. 100.  See further Case T-360/90 E.ON Ruhrgas and E.ON v Commission, at para. 98.

  [23]   See Ruling, at para. 129.

  [24]   See Ruling, at para. 97.  See further Decision, at para. 635.

  [25]   See Ruling, at paras. 121.

  [26]   See Ruling, at paras. 97.

  [27]   See Ruling, at para. 122.

  [28]   See Ibañez Colomo, P., “GC Judgment in Case T-472/13, Lundbeck v Commission: on patents and Schrödinger’s cat”, at Chillin’ Competition, 13 September 2016, available at

  [29]   See Case 27/87 SPRL Louis Erauw-Jacquery v La Hesbignonne SC.

  [30]   See Case 262/81 Coditel SA, Compagnie generale pour la diffusion de la television, and others v Cine-Vog Films SA and others.

  [31]   See Case 258/78 Nungesser v Commission.

  [32]   See Ruling, at paragraph. 335.

  [33]   See Rumsfeld, D., Known Unknown:  A Memoir, Sentinel, 2011.

  [34]   See Ruling, at para. 350.

  [35]   See Ruling, at paras. 451 ff, in particular, at paras. 458 and 460.

  [36]   See Ruling, at paras. 354; 355.

  [37]   See Federal Trade Commission v. Actavis, 570 US (2013).

  [38]   See Ruling, at paragraph 353.

  [39]   See Decision, at para. 640.

  [40]   See Ruling, at paras. 354; 383; 414.

  [41]   See Decision, at paras. 6; 788; 824; 874; 962; 1013; 1087.

  [42]   See Ruling, at paras. 354; 383; 410.

  [43]   See Ruling, at paras. 354; 383.

  [44]   See Decision para. 693.

  [45]   See Ruling, at para. 336.

  [46]   See Ruling, at paras. 355; 360.

  [47]   See Federal Trade Commission v Actavis 570 US 2013.

  [48]   See Ruing, at para. 341.

Stacking the Deck -Again! Clinical Negligence Litigation Cost.

Back in the early part of 2016 I looked at how changes to the costs rules since April 2013 had benefitted Defendants at the expense of Claimants. I pointed out that many had commented that successive governments had been increasingly pro-Defendant in their reforms.

The announcement earlier in 2016 by the then Health Minister, Ben Gummer, seemed to be consistent with that view insofar as Mr Gummer had announced that the government intended to bring in fixed costs for all litigation cases worth £250,000 or less, including clinical negligence, and these reforms were to be introduced in October 2016.

Well, the long awaited consultation on fixed costs initially set for the end of 2015, then put back to early 2016, is still nowhere to be seen!

However, recent news reports seem to suggest that the government has reviewed the idea of fixed costs for clinical negligence cases and now intends to set the level for inclusion in the fixed costs regime for clinical negligence cases of £25,000 or less (not £250,000).

What will actually happen?

The consultation paper is still awaited and the government will need to review the outcome of the consultation before proceeding to introduce their reforms.

The national Law Society has welcomed news of some reversal of thinking by the government, but the Law Society has highlighted the difficulties in imposing fixed costs in clinical negligence cases where complex medical issues are involved. Such a regime should only apply to modest value claims of £25,000 or less where liability has been admitted.

Equality before the law is a fundamental principle behind our justice system. Fixed costs will save Defendants money at the expense of Claimants. In cases against the NHS, the State is ultimately responsible for paying successful Claimants and for paying for the defence in claims against NHS Trusts.

The State has deep pockets. Hence, the playing field is not equal now and creating further costs obstacles for Claimants will make the current lack of equality even worse.

Let us not forget that legal aid for clinical negligence cases was removed in April 2013, save for a small minority of cases. No legal aid and the introduction of fixed costs – do you now wonder why I title this commentary, “Stacking the Deck – Again!”


Recreational Marijuana’s Economic Advantages

As Seattle City Attorney Pete Holmes has famously touted, marijuana prohibition and the war on drugs has failed.[1] Evidence does not suggest that the War on Drugs reduced drug-use rates or drug dependency.[2] At any given time, there are at least 137,000 men or women locked in prison or held in jail on drug possession charges, according to the ACLU and Human Rights Watch.[3] Additionally, the ACLU and Human Rights Watch report, citing FBI data, suggests that police and local law enforcement nationwide make more arrests for marijuana possession alone than for all violent crimes combined.[4] The local evidence suggests the same; in the first two years, law enforcement saw a decrease in work load anecdotally attributed to lack of those possession arrests, and now the Washington State courts are seeing the same.

The Washington recreational marijuana market has now been in effect for three years, and while the law has changed rapidly during that time, the economic benefits have clearly proven themselves. As the Washington and Colorado markets expanded, being the first two states to legalize adult and recreational use of marijuana products, other states began to take notice of how lucrative the legalized marijuana market could be, as both Washington and Colorado generated nearly 70 million dollars in tax revenue alone in each their first complete fiscal years.[5] It is clear that recreational marijuana turned the tide of the War on Drugs, and forced it to become an economic benefit that is becoming increasingly enticing to the rest of the nation.

Washington State’s Weed Economy

While Initiative 502 was voted for in November of 2012, the first Washington state producer and processor licenses were not issued until March 5, 2014.[6] In the 2014 fiscal year[7], a total of 279 producer/processor licenses were issued, and the Washington State Liquor and Cannabis Board (WSLCB) only generated 1.78 million dollars in total marijuana related income, which is impressive for how small the industry was, and for only 3 months of revenue generated during that fiscal year.[8]

The 2015 fiscal year, however, as the first complete fiscal year after legalization, showed real promise for the legalized marijuana industry:  total shelf price[9] sales generated nearly $260 million dollars, and generated $64.63 million dollars in tax revenue alone, as well as $1.08 million in just licensing fees and other related costs while the state was operating at only a 25% excise tax.

The 2016 fiscal year for Washington compounded on industry success, nearing $1 billion dollars of total shelf price sales, and created a total tax obligation of almost $186 million.[10] Much of this increased tax revenue can be attributed to the implementation of Senate Bill 5052 and House Bill 2136 in July of 2015, which, among other things, changed the state excise tax from 25% to 37% at the point of sale, and merged the less regulated medical marijuana market with the regulatory system established by I-502.

As of October 12, 2016, the WSLCB has issued 172 producer licenses, 894 producer/processor licenses, 131 processor licenses, and 445 retail licenses, which have combined to generate nearly $500 million dollars of total sales in less than four months.[11] It stands to reason, then, that the Washington market will generate well more than $1 billion dollars in total sales, leaving the state with (if sales in Washington remain on this course for the rest of the year), with around $300 million dollars of tax revenue for this year alone.[12]

Washington is not the only state that has had incredible success with regulated marijuana. Colorado has seen similar sales numbers creeping on $1 billion dollars a year and generating around $70 million in tax revenue in 2015. With five states voting on recreational legalization and 4 voting on medicinal legalization this November, it is clear that the legalized marijuana market will be a multibillion dollar industry nationwide, and the lure of tax revenue in the hundreds of millions seems to be convincing even the most historically conservative states that legalization is not only valuable economically, but is a better system than prohibition.[13]

A Better Way

With the plethora of tax money created by the legalization market, grander steps toward reducing youth access to drugs, education, and crime have occurred in the last three years than the strategies implemented by the war on drugs. According to the I-502 Fiscal Note[14] produced by the state, over the five years from the implementation of I-502 in 2012 to 2017, only $5 million dollars will be used by the WSLCB for program administration, whereas $44 million is to be dedicated to marijuana public health education, $68 million on youth drug prevention, and a staggering $244 million on health care. In fact, the state estimates that the funds generated could provide for services for up to 600,000 patients per year, and could cover a five-year average for insurance for 83,000 enrollees.”[15]

Legalization has also had significant impacts on the reduction of crime: According to Washington State Administrative Office of the Courts, court filings for low level marijuana offenses for adults over 21 has dropped 98% since the approval of I-502.[16] Additionally, according to the Crime in Washington Report compiled by the Washington Association of Sheriffs and Police Chiefs, marijuana law violations decreased 63%, and the number of marijuana related convictions has dropped 81%.[17] Legalization of marijuana has not merely freed up police enforcement and the courts however; violent crime declined by 10% statewide, and the murder rate decreased by 13%.[18] [19] Youth access and use rates have also remained steady, despite legalization, and traffic fatalities involving marijuana reported by Washington Traffic Safety Commission have seen a 4% decrease.[20] [21]

As regulation in Washington becomes increasingly robust and license standard enforcement becomes more effective, these numbers should continue to decline and profits from the industry should continue to rise. While the market may eventually level out, the sky seems to be the limit, as the WSLCB plans to continue to accept applications for new businesses.

Washington’s first three years of legalized marijuana has certainly had its struggles (Washington remains the most highly regulated of all the states that have legalized recreational marijuana) but above all else, it seems that Washington voters may be right; legalization is a better way than prohibition, and the Washington economy proves that recreational marijuana has turned the War on Drugs into a very convincing economic equation.

Anne van Leynseele, founder of NWMJ Law, led the evolution of what legal services were needed in the newly formed cannabis industry and identified how to best use her business and legal abilities. A critical step was partnering with noted cannabis trial lawyer, Aaron Pelley. Their complimentary practices brought together the power of both litigation and transactional law experience and diversified what NWMJ Law now provides.  Anne shares the responsibility with a great team of lawyers, each of them skilled in their own practice areas.


[1] Pete Holmes has been recorded claiming that the war on drugs has failed, and that Seattle and Washington generally has shown that legalized marijuana is a better way, both at Hempfest 2011, and more recently at the King County Bar Association new attorney Swearing-in ceremony in 2016.
[2] Tess Borden of Human Rights Watch: Interview
[7] Please note that the WSLCB’s fiscal year runs from July 1 to June 30.
[9] The WLSCB considers shelf price as sales price and tax combined
[11]; accessed October 14, 2016.
[13] California, Arizona, Maine, Massachusetts and Nevada are voting on recreational use, and Arkansas, Florida, Montana and North Dakota are voting on medicinal marijuana provisions.
[14] The I-502 Fiscal Note uses projected numbers and estimations based on the data available at the time to project budgets through 2017, so based on the success of the industry, these numbers could be even larger at present.
[19] It is important to note, however, that the data does not establish causation, but it is significant evidence that legalization of marijuana did not increase crime rates, as opponents to legalization seemed to believe it would.

The Fate of Pharma Patents in U.S. Inter Partes Review Proceedings

As part of the 2011 America Invents Act,[1] the United States Congress created a new process for challenging the validity of issued U.S. patents in the Patent Office (before the Patent Trial and Appeal Board –“PTAB”).  Known as an Inter Partes Review (“IPR”), this process allows third parties to pursue a “mini-trial” against the validity of the patent at issue based solely upon prior art.

This article reviews the IPR process as compared with a federal district court trial on validity, surveys how pharma patents have been faring in the IPR realm, and highlights our team’s recent win before the PTAB regarding a pharmaceutical formulation patent that was challenged as allegedly obvious.

I. Background

The branded pharmaceutical industry relies on patents to provide a period of exclusivity for innovative medicines and thus justify their large and often risky expenditures on research and development.  As a result, the branded pharmaceutical industry has championed the importance of patents.  In contrast, the fast-moving technology and electronics industries have often expressed concerns about costly patent litigation.  These concerns have been magnified by the advent of “Non-Practicing Entity” litigants (otherwise known as “NPEs” or more colloquially “patent trolls”).  These trolls, who make no products, use patents they own to seek damages from alleged infringers as a business model.

In response to these concerns, Congress enacted the IPR process as a supposedly quick and inexpensive way for the public to challenge the validity of patents in the United States Patent Office.

A. Summary of The IPR Process

In broad overview, the IPR process provides, inter alia, for:

  1. an initial request for review from a “Petitioner” (who can be anyone) stating the reasons for alleged patent invalidity;[2]
  2. an optional preliminary response from the Patent Owner stating why a review should not be initiated;[3]
  3. a decision from the PTAB regarding whether to institute a review of the patent, which requires a determination that there is a reasonable likelihood that the petitioner would prevail with respect to at least one of the claims;[4]

And, if the review is initiated:

  1. a short period of limited “discovery” where experts may be deposed;[5]
  2. a more substantive response by the patent owner – which can include argument about the prior art, expert declarations and evidence of commercial success;[6]
  3. a short (half day or so) hearing (“trial”);[7] and
  4. an ultimate determination within a statutory period of one year.[8]

Although rare, the Patent Owner may amend its claims[9] in an attempt to avoid invalidity.

B. Differences From Federal Court Invalidity Proceedings

IPRs differ from federal district court cases on validity in several key aspects, including:

(a) who may attack the validity of the patent (anyone may petition for an IPR versus only those with “standing” in district court);

(b) the standard of proof required to invalidate the patent (a mere “preponderance of the evidence” in an IPR versus the higher standard of “clear and convincing evidence” in district court);[10] and

(c) the way the patent claims will be construed (“broadest reasonable construction” in an IPR versus a narrower construction in the district court).[11]

These differences arguably make the IPR a forum where patent invalidity is more likely to be found than in district court.

C. The New “IPR Patent Trolls”

Ironically, the IPR procedure that was created in part to tame patent trolls has engendered a whole new type of patent troll – those without standing in federal court that seek to use the IPR process to gain financial reward.  These new “IPR patent trolls” are not business competitors to the patent owner.  Instead, they are third parties (including hedge funds and related entities) that are empowered by the statute to initiate and pursue an IPR.  It has been speculated that they may be using that power to seek financial gain by either shorting the stock of the patent owner or obtaining some other financial settlement.

II. The Statistics

Since the AIA’s enactment, the Patent Office has received over 5,000 Petitions to review patents.[12]

As of August 2016, 3,529 petitions have been completed, with 1,807 of those instituted.  Of those instituted, Petitioners have invalidated around 70% of all challenged claims.[13]

With respect to biotechnology and pharmaceutical patents, there have been 331 petitions, 207 of which have been instituted.[14]  Among biotechnology and pharmaceutical patents, the invalidation rate has been approximately 45%.[15]

III. A Pharma IPR Win at the PTAB

Despite the statistics and the lower standard of proof for invalidity, patent owners can and do win IPRs.

Case in point: IPR No. 2015-00988, Coalition for Affordable Drugs II, LLC v. Cosmo Technologies Ltd.

In this IPR, an entity formed by hedge fund manager Kyle Bass and his associates – that otherwise would not have had standing in federal court – brought a petition to initiate an IPR and invalidate U.S. Patent No. 6,773,720 (“the ’720 patent”) in the Patent Office.

A. The Invention of the ’720 Patent

The ’720 patent is directed to an orally-administered, controlled release formulation of the drug mesalamine.  Mesalamine treats ulcerative colitis – an inflammatory condition of the large intestine.  Mesalamine provides its therapeutic benefit at the site of inflammation on the interior surface of the large intestine.  It does not provide therapeutic benefit when absorbed systemically into the bloodstream.

Thus, one challenge to making an effective mesalamine oral treatment is that it must release drug in and throughout the colon – bypassing the stomach and small intestine – and it must maintain relatively even or “controlled” drug release along the length of the large intestine.  An added dilemma for the formulator is that oral dosage forms of mesalamine must contain large amounts of the drug to be of benefit (over 1 gram) – leaving little space for excipients.  Yet, it is the excipients that are necessary to control the release of the mesalamine.

Working within these constraints, the inventors of the ’720 patent created a two-matrix formulation that uses minimal amounts of excipients to control the release of large amounts of mesalamine – slowly and in the right place in the colon.

B. The Petitioner’s Challenge

The Petitioner’s challenge to the validity of the ’720 patent turned on two prior art references – the Leslie reference from over 23 years before the invention of the ’720 patent that did not mention mesalamine and the Groenendaal reference from 10 years before the invention.  Although neither of these references referred to each other or spoke about a two-matrix formulation, Petitioner argued that there would have been a general motivation to combine the two references (simply because they both involved controlled release) and once combined the elements of the ’720 patent would be readily revealed.

C. The PTAB’s Analysis: No Invalidity

Although the PTAB did grant the initial request for review, after full consideration of the developed record, the PTAB concluded that the Petitioners had not proven invalidity by a preponderance of the evidence.

In coming to that conclusion, the PTAB considered numerous distinctions from the prior art, including whether the particular chemical class of “waxes”  called for in the challenged claims were disclosed in the prior art.  The Board rejected the Petitioner’s broad statements that the prior art disclosed “waxy” materials and distinguished those from the actual “waxes” recited in the claim.  The PTAB also found an absence of a motivation to combine the references; and also noted the complexity of formulation science – as conceded by Petitioner’s expert during deposition.  Further, the PTAB credited the commercial success of the patented invention as an objective indicia of non-obviousness.

D. Take Home Lessons

There are many take home lessons from the experience.

First and foremost, IPRs involving pharmaceutical patents can be won by patent owners.  In many ways that should not be a surprise.  The pharmaceutical and chemical sciences have repeatedly been recognized to be complex and unpredictable[16] – hallmarks of non-obviousness.

Second, identifying clear differences between the prior art and the claimed invention – and buttressing those differences with solid evidentiary proof in terms of literature and expert testimony – can help the PTAB understand why a claimed invention truly is different.

Third, although some IPR decisions seem to discount commercial success and other objective indicia of non-obviousness, this form of evidence should not be ignored by patent owners.  When presented to the PTAB, it can prove helpful.

Fourth, as the IPR process unfolds, patent owners should not recoil from reiterating arguments that were apparently rejected at the initiation stage.  The PTAB seems willing to reconsider its initial views when new information is presented.

Fifth, one of the complexities of an IPR proceeding is that the witnesses are not actually observed at trial by the PTAB judges.  While excerpts of deposition testimony are cited in briefs, there is no live testimony.  For this reason, deposition testimony should strive to elicit clear admissions and important points from the other side’s experts.

From the perspective of the petitioner, a claim of invalidity should be based upon prior art that is as close to the patented claim as possible.  Where one needs to stretch the prior art’s disclosure to simulate the claim, proof of invalidity is likely lacking.

IV. Parting Thoughts

As with many “solutions” to problems in the law, the IPR solution to supposedly “weak” patents and “patent trolls” has created concerns of its own.  A procedure that permits important issued patents to come under attack, under a lower standard of proving invalidity, has the very real potential to weaken the patent system and discourage investment in important new research.  Whether Congress should maintain the lower “preponderance of the evidence” standard for IPRs is a topic that should be discussed and debated.  However, as things currently stand, the Patent Office has the important task of balancing the concerns raised by so-called “weak” patents with the goals of the patent system itself – promoting research and innovation.

[1] Pub. L. No. 112-29, 125 Stat. 284 (2011) (also referred to as the “AIA”).
[2] 35 U.S.C. §§ 311 and 312.
[3] 35 U.S.C. § 313; 37 C.F.R. § 42.107.
[4] 35 U.S.C. § 314; 37 C.F.R. § 42.108.
[5] 35 U.S.C. § 316(a)(5); 37 C.F.R. § 42.51.
[6] 35 U.S.C. § 316(a)(8); 37 C.F.R. § 42.120.
[7] 35 U.S.C. § 316(a)(10).
[8] 35 U.S.C. § 316(a)(11).
[9] 35 U.S.C. §§  316(a)(9), 316(d); 37 C.F.R. 42.121.
[10] See 35 U.S.C. 316(e) (“In an inter partes review instituted under this chapter, the petitioner shall have the burden of proving a proposition of unpatentability by a preponderance of the evidence”) and Cuozzo Speed Techs., LLC v. Lee, 136 S. Ct. 2131, 2144 (2016) (“the burden of proof in inter partes review is different than in the district courts: In inter partes review, the challenger (or the Patent Office) must establish unpatentability ‘by a preponderance of the evidence’; in district court, a challenger must prove invalidity by ‘clear and convincing evidence.’”).
[11] See Cuozzo Speed Techs., 136 S. Ct. at 2142 (claims interpreted in broadest reasonable manner for an IPR).
[12] Patent Trial and Appeal Board Statistics, last updated August 31, 2016, available at
[13] Id.  This excludes instituted IPRs that were terminated prior to a final decision from PTAB.
[14] Id.
[15] M. Grewal, J. Hill, and K. Zalewski, “Trends in Inter Partes Review of Life Sciences Patents,” 92 BNA’s Patent, Trademark & Copyright Journal 3 (June 17, 2016).
[16] See, e.g., Eisai Co. Ltd. v. Dr. Reddy’s Labs., 533 F.3d 1353, 1359 (Fed. Cir. 2008) (“To the extent an art is unpredictable, as the chemical arts often are, KSR‘s focus on [ ] ‘identified, predictable solutions’ may present a difficult hurdle because potential solutions are less likely to be genuinely predictable”);  Abbott Labs. v. Sandoz, Inc., 544 F.3d 1341, 1351 (Fed. Cir. 2008) (extended release formulation not obvious: “difficulties in predicting the behavior of any composition in any specific biological system.”);  Eli Lilly & Co. v. Generix Drug Sales, Inc., 460 F.2d 1096, 1104 (5th Cir. 1972) (paraphrasing Churchill, the court noted that chemical compounds present a “riddle wrapped in a mystery inside an enigma”).


Leaving the EU – what this means for you and your business

Now that the dust is settling on the UK’s decision to leave the EU, our clients are asking what this means for them.  We are the first member state ever to  leave the European Union and as such, the result has ignited much uncertainty and debate about what lies ahead.

Change always brings opportunities, as well as challenges, and we are focused on helping our clients understand how these changes can benefit their business during the period of transition ahead.

A recent survey we commissioned suggests that only 20% of businesses had set in place a continuity plan for the leave vote. In the public sector, there is concern about what will happen to staffing arrangements as well as EU-funded collaboration projects.  We understand that there is much uncertainty at present, but we will continue to support and provide innovative solutions to help our clients invest and grow.

Of course, it’s not only businesses that are affected.  Exit from the EU will likely have a knock-on effect on a range of private and family law matters which are currently governed by a system which in many areas combines both EU and domestic legislation into an integrated European framework.

Whilst it is not clear what the exit will look like or how we will take forward the laws that the UK has adopted over the last 40 years, we do know that there will be opportunities coming out of these changes and we will be supporting our clients in understanding how these can be used to their advantage.

In this article, I explore some of our key sectors and what the implications may be for them of leaving the EU.

Real Estate

Real Estate markets, whether commercial or residential, always prefer certainty. The last few months have led to a slowdown in transactions while people awaited the outcome of the Referendum. In some recent cases, transactions have been entered into with options to determine depending on the result of the vote, and those agreements may now be determined. Now that we know that the Leave vote has won, we expect to see the Real Estate markets to pick up rapidly. Banks are still in the market to lend to the right product, and there is a significant amount of private equity cash available for property transactions. However, there may be some weakness in areas involving prime offices if companies start relocating their HQs.

Private Law

Since 17 August 2015, we have been coming to terms with new EU legislation for succession (known as Brussels IV). Paradoxically, this system is intended to unify the succession laws which apply to an estate, and now, we have voted to leave just at the point when the member states choose to change things for good!

That said, the UK opted out of the full implementation of the legislation, along with Ireland and Denmark, so the impact strangely has been simplified as there was some uncertainty as to how the legislation applied to the UK. The intention is that EU citizens are able to make an election of the law of the jurisdiction of their nationality to govern the whole of their estate (including foreign property located in another EU state). Post-Brexit the UK is clearly a ‘third state’ under the Regulation, like the USA

This means less flexibility in the choice of succession rules and potentially more tax, although double taxation treaties should continue to apply. Our EU neighbours mainly favour a succession system which includes forced heirship, and we could find ourselves in a position where there is less choice on the ultimate distribution of foreign immovable assets.


Employment law is unlikely to see too many dramatic changes as the UK leaves the EU. Despite the claims that businesses are stifled by EU labour laws, the fact is that many Employment law rights either originated in the UK or have become deeply embedded in UK law as the UK’s attitudes to social issues have evolved. A move to scale back all but the most minor Employment law rights would, in all likelihood, be politically unpopular.

In addition, potential changes could be severely limited by the subsequent trade deal negotiated – other non-EU countries such as Norway and Switzerland have not in practice been able to free themselves of many EU labour laws. In several areas, such as data protection, we are likely to produce laws that mirror EU legislation to ensure we can conduct business effectively.

Such changes as there are could be seen in the areas of collective consultation rights, clarification on Working Time rights such as paid holiday and a repeal of the 48-hour limit, tweaks to the Transfer of Undertakings (Protection of Employment) Regulations 2006, and potentially more significant changes to/removal of the Agency Workers Regulations 2010.

As well as the immediate impact on markets and the business outlook for employers, the referendum result will also throw up longer-term issues, such as the migration of staff in and out of the UK and a potential re-run of the Scottish referendum. Unfortunately, the lack of a clear indication as to what any exit deal would look like makes it very difficult for businesses to plan for it in any practical way at the present time.

Banking and Finance

The financial markets and the banking sector hate uncertainty. The government needs to move quickly to reassure the business community by setting out a clear plan to replace existing trade and other arrangements with the EU and the world as a whole.

Particularly in the short term, the role of the Bank of England will be key. At a time when the monetary tools available to them are already limited, they need to find a way to protect the pound and keep interest rates at a level that enables companies to continue to borrow and invest in what will hopefully be a prosperous economic future for the UK.


The Referendum campaign highlighted a fundamental lack of objective data regarding the impact of EU membership on our healthcare system, and therefore the effects of an exit. However, staffing is likely to be impacted as the NHS, and social care are reliant on overseas migrants to help alleviate intense staffing pressure.

The London location of the EU Medicines Agency has been cited as a positive factor in the NHS’s successful positioning of its R&D capabilities, attracting overseas investment and funding. If the EMA must now relocate, the long-term impact on trials revenue and participation will depend on the strength and depth of relationships already established.

European systems have influenced several of the new models of care programmes in the NHS.  Many independent healthcare operators have pan- European activities. Uncertainty in the short term about implications of an exit could impact collaboration and appetite for financial risk in organisations supporting the NHS.


It is impossible to ignore the fact that the higher education sector, which is presently reliant on the EU as a reliable source of funding, in the form of students, research grants, and capital finance, faces a challenging future, given the uncertain nature of the relationship between the UK and the EU. In the next five years, we may well see a more innovative approach to funding and collaboration required, with institutions looking further afield for support, or collaborations with the private sector.

Intellectual Property

For the moment it is business as usual and trade mark and design owners should not panic – European Union Trade Marks and Registered Community Designs remain valid in the UK, and there is no immediate loss of IP protection.

Once the UK formally gives notice to exit, the EU negotiations will begin on the status of EU marks in the UK and whether any transitional provisions will be required to grandfather across EU trade mark and registered design rights into the UK.


There maybe harmful consequences for major infrastructure projects as much of the funding comes from Europe including Crossrail and HS2.  How such projects will be funded in the future will apparently be included in the Brexit negotiations.

It is impossible, though, to predict what the wider impact will be on our economy or the property market at this stage but if migration is reduced, then the pressure on housing should be reduced and the housing needs assessed more accurately.

Information Governance

Most of the laws in information governance are derived from European legislation. The Data Protection Act, the Privacy and Electronic Communications Regulations, the Re-use of Public Sector Information Regulations, the Environmental Information Regulations – all of these are examples of UK laws derived from EU directives.  For primary legislation, such as the DPA, leaving the EU will have no immediate effect.  For secondary legislation, such as the EIRs, the situation is more complicated.  These were made under powers derived from the European Communities Act 1972, which is the statute that governs our membership of the EU.

Family Law

Leaving the EU will have a knock-on effect on a range of family matters governed by the current system, which pulls together strands of EU and domestic legislation into a single Family law regime. Changes are likely to be felt most keenly by international families.

In terms of jurisdiction in divorce matters, the current rule of “first in time” as to where proceedings will be dealt with will disappear. Parties will therefore potentially be afforded greater flexibility as to where they choose to divorce. However, matters could become increasingly costly if the proposed jurisdiction is contested and, in these circumstances, parties may well find themselves litigating over jurisdiction issues before the main proceedings are dealt with at all.

Enforcement of existing domestic Orders concerning maintenance, child contact, and domestic violence will also be affected. EU legislation currently works with domestic legislation to provide a relatively simple framework for enforcement of such Orders in other EU member states. Brexit means that the system will not operate as such any longer, thereby potentially undermining the current system of mutual co-operation between Courts.

The law governing international child abduction would also see some changes, albeit that these would be less significant. This is because the main international legislation governing this area is found in the 1996 Hague Child Protection Convention and the 1980 Luxembourg Convention, which will remain in force. However, changes incorporated into these Conventions by later EU Regulations will fall away, leaving gaps to be filled at a later stage. The child abduction regime may be weakened in the interim until a comparable system is put back into place through re-negotiation of bilateral agreements with different states to replicate the lost provisions.

For more information on what leaving the EU will mean for your business visit or email [email protected]

New Standards for Cosmetic Surgeons

New GMC Guidelines

As of June 2016, new guidance from the GMC regarding doctors carrying out cosmetic procedures will come into force. The new guidelines will highlight the need for accountability from the doctors involved in the treatment, and consideration of patient safety at all times. Various cosmetic procedures have come under fire in the last few years, with the 2010 PiP implant scandal one of the industry’s better documented failings. Despite the bad press, the cosmetic sector is a rapidly emerging market which is now widely available, and prospective patients are faced with more options than ever before.

In the wake of recent problems, Professor Sir Bruce Keogh, National Medical Director of NHS England, has led an independent review of the cosmetic industry. This review was tasked with identifying the current risks associated with cosmetic interventions and how best to protect the public in this area. As a result of the review, the GMC’s new guidance for doctors carrying out cosmetic procedures will come into force in the summer. The guidelines apply to all cosmetic procedures, including both surgical and non-surgical treatments, with the aim of improving standards and making the ethical responsibilities of the industry clear to all doctors who work within it.

Thankfully, the majority of doctors in this field already practise ethically and to a high standard. However, the cosmetics sector is not without examples of unsafe practices, poor follow-up care and inappropriate marketing campaigns. The new guidelines are in place to protect patients from these more unsavoury elements, and to hold any unethical practitioners fully responsible for their actions. I will now take a look at some key areas in the new guidelines, and what they mean for practitioners.

Responsible Advertising and Marketing

One of the major changes coming in the summer will be the tighter regulation of advertisements. Though cosmetic surgery adverts will not be banned, as some campaigners have called for, they will have to obey certain rules. The adverts are no longer allowed to entice potential customers with cut-price deals, and marketing campaigns can no longer offer cosmetic surgery as a prize in a competition. These outlawed practices are designed to encourage people to make quick decisions without considering all of the implications – something that the new guidelines want to put an end to in the interest of patient safety. In addition, adverts are not allowed to make any unjustifiable claims. Patients must be presented with accurate information, and able to make their decision in their own time without feeling under any pressure to respond to outside influences.

Time for Reflection

Linked to the implications of the advertising guidelines is the rule that patients must be able to make fully informed decisions about prospective cosmetic procedures, and able to change their mind at any point. This means that patients cannot be rushed into their treatment; they must be able to reflect on their choice given all of the available information, including any associated risks. Under no circumstances should practitioners encourage patients to undergo these procedures lightly or without serious consideration.

It is often thought that a significant proportion of patients seeking cosmetic procedures may be appropriately regarded as vulnerable; from June, doctors will be required to consider the psychological needs of their patients, including whether the patient would benefit from a referral to another professional colleague. This is particularly important when it comes to the treatment of young people; their mental health in relation to the procedures will need to be fully evaluated, and sufficient time needs to be given to them to ensure that their treatment is right.

Practically, the amount of time given to a patient for their decision will depend on their specific circumstances. These include the invasiveness of the surgery, as well as its complexity, permanence, and risks. Above all, the patient needs to know that they can change their mind at any point; they should not feel pressured by advertising or by medical professionals themselves.

Fully Informed Consent

An integral part of the new guidelines is the requirement for the patient’s fully informed consent. It will be the responsibility of the doctor carrying out the cosmetic procedure to personally discuss the procedure with the patient and obtain their consent. This cannot, under any circumstances, be delegated to someone else. These is no longer any place for prescribing injectable cosmetic medicines over the telephone, via video link, online or at the request of others; the doctor may only prescribe treatment in person, and must carry out a physical examination of the patient first. In addition, the doctor must be satisfied that the patient’s request for cosmetic intervention is entirely voluntary, and not the result of any sort of external pressure.

Continuity of Care

As already mentioned, doctors must ensure that patients are fully informed as to the process and risks of the procedure, but the patient must be given information to help them beyond the treatment itself. This information includes contact details for the right person to get in touch with in the unfortunate scenario that something goes wrong with their procedure, to ensure that they are fully supported for as long as they need to be.

Patient Safety

A couple of final points of note are that doctors will be required to make full and accurate records of  all consultations with their patients, and that doctors must identify and immediately act on any patient safety concerns, including fully contributing to programmes designed to monitor quality and outcomes of the treatment. All of this is to make sure that there is never any lack of information regarding the procedure, meaning that any issues or complications can be acted upon quickly and correctly.

Final Thoughts

As I have said, many doctors already practising cosmetic procedures do so with good ethical standards and care for their patients, but there are also some who do not have the same considerations. These guidelines look to be a step forward for the industry, making it very difficult for those doctors who may have acted inappropriately in the past to continue to do so. The emphasis on patient care is important, and if the professionals working in the industry ensure that everything they do is with their patients’ interests at heart, then these guidelines will have gone a long way towards making cosmetic procedures safer for all involved.

Common Terms in Pharmaceutical Trademarks

It is usual that pharmaceutical trademarks contain commonly used terms, so they are formed by the combination of elements such as prefixes, suffixes or commonly used words that evoke somehow an idea about the properties of the product, its active principles, and its therapeutic function. They also may refer to a component of the medicine or the organ for which they are prescribed.

Terms are considered commonly used for two reasons: either for being part of the several marks or for being evocative of the product or any of its features. By common usage anyone is free to include them in a mark, provided that it is not confused with other marks of other owners.

For example, a prefix commonly used in Class 5 is the prefix CORTI that evoke the active substance corticosteroid or the word “cortisone”. The prefix CORTI is present in the formation of numerous registered trademarks owned by different owners, such as: CORTIFLEX, CORTIDERM 10, CORTIMED, CORTICREM, CORTIFENOL[1], etc.

The Court of Justice of the Andean Community has established in a precedent that the prefixes, suffixes, roots or endings commonly used in the marks cannot be subject to monopoly or exclusive use of a single person since they are usual words which its use by the general public can’t be prohibited.

Usually it is argued that because the signs identify products that directly affect health and have consequences on the human body, the consumer will have a higher level of attention and special care when purchasing the pharmaceutical products. This has been recognized in diverse jurisprudence of INDECOPI where stated that “in the case of pharmaceuticals referred to the signs in question, it is reasonable to assume that the consumer, when purchasing such products, would make a close examination based on their needs”[2].

However this is not enough to dismiss the risk of confusion because in the pharmaceutical trademarks that share commonly used terms, whose names could prove to be very similar, the consumers themselves might be induced to confusion, i.e., it may acquire a product in the belief that it is purchasing another, which is known as direct confusion or might think that the product has a distinct commercial origin than the real one, what is called indirect confusion.

The Court of Justice of the Andean Community in the Process 08-IP-2013 has noted that:

“What comes to protecting, by avoiding trademark confusion, is the health of the consumer who for confusion when asking for a product and negligence of the dispatcher, he may receive one with similar phonetic but different composition and purpose. If the requested product is intended for flu treatment and the delivered one is for the amebatic treatment, the consequences for the consumer can be dire.

We must consider that what has been dominating in our countries is the culture of the ‘personal healing’, according to which a large number of patients self-medicate because they have heard about a product in advertisement or received an indication from a third person. It is not considered that every human body has a different reaction to the same drug, and the self-medication can lead to misleading or confusion at the time of acquisition because the similarity between the two signs.”

This approach has been reiterated in several sentences of the Andean Court, such as the Process 30-IP-2000, where is stated:

“This Court is inclined to the thesis that when regarding pharmaceutical trademarks, the examination of confusing similarity should have a more exhaustive study and analysis, avoiding the registration of trademarks whose names has a close similarity to avoid precisely the consumer requests a product instead of another, which in certain circumstances can cause irreparable damage to human health, especially when in many establishments, even drugs of delicate use, are dispended without a prescription and only with just the advice of the pharmacist on duty”.

Also in Process No. 68-IP-2001, the same rigorosity was followed for the comparison between signs in the examination of confusing similarity, concluding that:

“In respect to pharmaceutical products, it is very important determine their nature, since some of them correspond to products of delicate application, which can cause irreparable damage to consumer health. Therefore, the recommendation in these cases is to apply, a rigorous approach in the analysis of the opposing marks that seeks to prevent any confusion in the consuming public because of the nature of the products identified with them.”

These arguments are based on the fact that the average consumer is not usually a specialist in chemicals and pharmaceutical issues and the acquisition and use of these products will usually lack of a permanent professional assistance.

The fact that the Specialized Chamber in Intellectual Property of INDECOPI considers that when dealing with pharmaceutical products, the consumer will take a decision following a careful consideration based on his/her needs, that is, that he or she will pay more attention when purchasing these products, doesn´t mean that there isn´t a possibility of confusion, even more if we put ourselves in the place of an average consumer, who doesn´t necessarily have knowledge of the components or properties of pharmaceutical products offered in the market, so he or she can easily fall into confusion when buying such products, in that sense, the consumer could buy in the drugstore a pharmaceutical product in the belief that he or she is buying another product, certainly because the phonetic similarities between the signs are so strong that lead to confusion and do not allow him/her to differentiate a product from another. In this case, not only the consumer would fall into confusion but also the same pharmacist, who may be confused by dispensing one product for another, precisely because of the phonetic and / or visual similarities between the marks.

An example of this is illustrated by the case of the application of the word mark “CORTIDEX”. This mark was applied by Inversiones Awl S.A.C. to distinguish pharmaceutical and veterinary products; etc. in Class 5 of the International Classification. Against this application, Laboratorios Chile S.A. files an opposition based on the ownership of the mark CORTIPREX that distinguishes products of class 5. In the opposition, Laboratorios Chile S.A. indicates that from the graphic and phonetic point of view, the marks are very similar because they share the word CORTI, and this term will be more easily remembered by the consumer public.

The Commission of Distinctive Signs, by Resolution No. 1085-2009/CSD-INDECOPI, declared unfounded the opposition and consequently granted the registration of the mark applied, stating that from the graphic and phonetic point of view the signs have a different sequence of consonants (C-R-T-D-X / C-R-T-P-R-X), thus they also differ in their final syllables (DEX / PREX), which determines that said signs generate a different pronunciation and a different overall visual impression. It is noted that the fact that the signs share the particle CORTI, this is not decisive to establish some kind of similarity between them, since this particle is part of the conformation of various registered trademarks in class 5.

By Resolution No. 0107-2010/TPI-INDECOPI, the Specialized Chamber in Intellectual Property confirms the first instance decision stating that “the initial particle CORTI present in the signs may refer to the term cortisone, which explains its frequent use in the conformation of registered marks in class 5 of the International Classification, as shown in the background Report. In this sense, it can hardly indicate a particular commercial origin”.

From our point of view the marks CORTIDEX and CORTIPREX themselves are confusingly similar, because in addition to distinguish some of the same products, from a graphic and phonetic point of view, the marks are similar since they share the prefix CORTI, which significantly affects the appearance of the opposing marks, even more taking into account that they share the same ending (EX) and the same sequence of vowels (O-I-E), generating a sound and a visual impact very similar, so this could lead to consumer confusion.

It is therefore very important that pharmaceutical trademarks have additional elements added to the common term, whether figurative or verbal, with sufficient distinctiveness to identify and distinguish the commercial origin of the product to avoid the risk of confusion, as also prevent the sign to become descriptive because that would make it not distinctive and therefore in consideration of the prohibition of registration of the Article 135 subparagraph e) of Decision 486 from the Andean Community which would make impossible their protection, but mainly because we must safeguard the health and life of the consumers, fundamental rights that are superior to any intellectual property registration.


[1] Trademarks mentioned in Resolution No. 0107-2010/TPI-INDECOPI dated January 13, 2010.

[2] Resolution  N° 0011-2009/TPI-INDECOPI from file N° 341709-2008

Clinical Trial Tragedy in France – Implications for trial sponsors and CROs


A clinical trial on healthy volunteers sponsored by Portuguese pharmaceutical company Bial came to an abrupt halt in early January 2016, when one of the trial participants was declared brain dead and five others were hospitalised soon after with organ failure and suspected brain damage. The trial drug, BIA–102474–101, was intended to target a range of diseases including pain relief. It was being tested in humans for the first time. French contract research organisation BioTrial (“CRO”) had been engaged by Bial (the “Sponsor”) to manage and host the trial at its Rennes trial centre, in France. The tragic outcome raises questions for organisations involved in sponsoring or conducting clinical trials, and is likely to lead to further reform of the clinical trials regulatory regime across the EU.

The legal framework for clinical trials in the EU

Clinical trials involving medicinal products for human use are governed in the EU by Directive 2001/20/EC (the “Clinical Trials Directive”). This framework legislation provides for additional implementing directives and guidelines. It also provides that an application for a Clinical Trials Authorisation (“CTA”) must be made to the national Competent Authority of any member state in which a trial site will be located. In the absence of any objection from the national Competent Authority within 60 days, the CTA will be deemed to have been given. Additionally, approval for the trial protocol must be sought from a Research Ethics Committee before enrolment of any trial subjects can begin. Inevitably, there are variations in the way in which the Clinical Trials Directive has been implemented into national law, leading to a lack of complete harmonisation across the EU. In order to improve the degree of harmonisation and reduce the administrative burden involved in organising cross-border trials in the EU, Regulation (EU) 536/2014 was adopted on 27 May 2014, repealing the Clinical Trials Directive (the “Clinical Trials Regulation”). It entered into force on 16 June 2014, but will take effect no earlier than 28 May 2016. So these upcoming changes did not apply at the time of the Bial trial, which took place under the regime of the Clinical Trials Directive.

Phase 1 clinical trials: “first in man”

Phase I trials, also known as “first in man trials”, are the first stage of testing in human subjects. Normally, a small group of 20–100 healthy volunteers will be recruited. This phase is designed to assess the safety, toxicity, pharmacokinetics[1] and pharmacodynamics[2] of a drug. These clinical trial clinics are often run by contract research organisations (“CROs”) who conduct these studies on behalf of pharmaceutical companies at a dedicated site where participants can be observed by full-time staff and receive 24-hour medical attention and oversight. Phase I trials also normally include dose-ranging studies, also called dose escalation studies to discover the dose at which a compound becomes too toxic to administer. The tested range of doses will usually be a fraction of the dose that caused harm in pre-clinical animal testing. Volunteers are typically paid an inconvenience fee for their time spent in the clinical trials clinic.

The TGN1412 trial

The oversight and monitoring of Phase 1 clinical trials was strengthened in 2007 following a previous tragedy in the UK. Healthy volunteer research subjects suffered multiple organ failure during a first-in-man phase 1 clinical trial at the private clinical trial research centre at Northwick Park Hospital in in 2006. The trial drug, code-named TGN1412, was being developed for the treatment of rheumatoid arthritis, leukaemia and multiple sclerosis. It was administered by injection over a period of minutes, rather than as an infusion over several hours. Following the very serious adverse reactions, the UK Secretary of State for Health convened an Expert Scientific Group under the chairmanship of Professor Gordon W. Duff to investigate and report back with recommendations. The final report of the Expert Scientific group in December 2006 influenced the provision of guidance in July 2007 by the Committee for Medicinal Products for Human Use (“CHMP”) of the European Medicines Agency on first-in-human clinical trials (the “EMA Guidance”).

The Bial Trial

The trial began on 9 July 2015. A CTA application had been filed with the French Competent Authority, the French National Agency for Medicines and Health Products Safety (“ANSM”), and had received deemed approval. Ethics Committee (“EC”) approval for the trial protocol has also been obtained. The protocol provided for a dose-ranging study in 128 healthy volunteers aged 18—55 years, who were each to be paid €1900. After some single ascending dose studies, four cohorts of volunteers were allocated to multiple ascending dose studies (at 2.5mg, 5mg, 10mg and 20mg).  These passed by uneventfully, with no serious adverse events (“SAE”) being reported to the French authorities. A fifth cohort (made up of eight volunteers) was allocated to receive the highest dose (50mg), administered once daily.

On day 5 of dosing this fifth cohort, serious complications began to develop. Within a week, volunteer 2508 (subsequently named as Mr. Guillaume Molinet) tragically died and five other volunteers from the fifth cohort had been left with suspected brain injuries. The only volunteers in the fifth cohort to escape unscathed were the two control subjects who had been administered a placebo. Various French authorities launched formal investigations which are currently underway, including the General Inspectorate of Social Affairs (“IGAS”),  the ANSM and the Ministry of Justice. The final reports are not yet available. However, interim reports have been released, which have identified procedural and clinical issues and which shed light on regulatory changes which are likely to follow in France and  across the EU.

Key findings – procedural issues

  • Delayed trial suspension

Mr Molinet had reported a headache within an hour of being dosed at 8am on day 5 of the study (10 January), and developed significantly slurred speech and double vision by that afternoon. The CRO’s doctor examined him at 3pm, but only prescribed a paracetamol. It was not until the CRO’s staff were challenged by other volunteers concerned by the continuing deterioration in his condition, that he was referred to the local hospital at 8.30pm, where he was admitted as an inpatient. Notwithstanding this SAE, the CRO proceeded to administer another dose of the trial drug to the remaining volunteers at 8am on day 6, without first checking with the hospital on the status of Mr Molinet. Curiously, although the CRO maintains that Mr Molinet had been hospitalised “at the first sign of light symptoms” and that the feedback received from the hospital the previous night had been “re-assuring”, in complete contrast, the letter from the CRO’s onsite doctor referring Mr Molinet to the local hospital describes more serious neurological symptoms (double vision, slurred speech, migraines) that had worsened through that day. The French authorities have criticised the decision not to suspend the trial immediately upon hospitalisation of a previously healthy volunteer with neurological symptoms, after ingesting a high dose of a previously untested drug that was known according to the protocol to interact with the central nervous system.

  • Failure to provide appropriate medical care

The second volunteer of the fifth cohort started to complain of similar symptoms on the afternoon of day 6. By this time, Mr Molinet had suffered a stroke and lapsed into a coma. Nevertheless, the second volunteer was also only given a paracetamol by the CRO’s doctor. On the morning of day 7, Mr Molinet tragically was declared brain dead and the second volunteer awoke with black eyelids. Nevertheless, the second volunteer was only offered another paracetamol and an ice pack by the CRO’s doctor. It was only on day 8,  when the second volunteer collapsed from dizziness, that he was finally hospitalised. The principles of Good Clinical Practice require the Sponsor and CRO to ensure that all volunteers who had taken the drug received appropriate medical attention and follow-up to ensure their safety. The French authorities are concerned that this did not happen, perhaps due to a systemic reluctance on the part of the CRO or Sponsor to acknowledge an emerging pattern.

  • Delay in reporting serious adverse event

The hospitalisation of Mr. Molinet occurred on day 6 of the trial, and clearly amounted to a serious adverse events as defined in the Clinical Trials Directive. Due to safety implications, strict reporting obligations require sponsors to be informed by CROs/principal investigators of serious adverse events within 24 hours (paragraph 29, Commission Communication 2001/C 172/01) (the so-called “CT-3” Communication). Hence, CROs tend to have robust measures in place that are triggered as soon as an SAE occurs. This is evidenced by the fact that within hours of the first volunteer slipping into a coma on day 6, Bial and the CRO had agreed to halt the trial. However, the sponsor also has an obligation to notify the national Competent Authority of any suspected, unexpected, serious adverse reaction (“SUSAR”). Where the SUSAR is fatal or life-threating, this must be reported “as soon as possible” and in any event within 7 days after the sponsor is made aware of the case. (paragraph 94, CT-3). Bial eventually notified the ANSM on day 9, four days after the hospitalisation of Mr Molinet. The French authorities are concerned that this did not comply with the obligation to notify “as soon as possible”, even though it was within the seven day longstop. They categorised the delay as a “major failure in the CRO’s crisis management”.

  • Failure to obtain informed consent

The Bial informed consent form (“ICF”) presented to every volunteer for signature promised: “You will be informed about any new significant information that could affect your willingness to continue the trial“. The remaining volunteers in cohort 5 were not formally informed of Mr Molinet’s hospitalisation when it happened on day 5, so were never given the opportunity to review their continued participation in the study before the next does of the trial drug was administered at 8am on day 6. While the CRO/Bial were in compliance with EU regulations, they appear to have chosen to ignore the standard set by their own ICF when deciding not to inform the rest of the group regarding the hospitalisation of a participant, before administering them with additional doses. This raises serious ethical concerns.

Key findings – clinical issues

The French authorities have also made various preliminary criticisms about clinical issues, including:

  • the volunteer screening (exclusion) criteria did not include a neuro-psychological assessment, even though the trial drug targeted the central nervous system;
  • the Sponsor’s pre-clinical animal test data appears to have been insufficient to justify progression to a first-in-man study;
  • the dose escalation from 20 mg for the fourth cohort to 50 mg for the fifth cohort was “too sudden”. It is unclear whether the Sponsor presented sufficient pharmacokinetic data to justify this; and
  • the choice of 50 mg as the highest does in the dose ranging study was heavily criticised, which was up to 20 to 80 times higher than that needed for the therapeutic mechanism sought to be achieved.

It is unclear why these points were not picked up by either the ANSM or the Research Ethics committee when evaluating the Sponsor’s CTA application. No doubt the full reports of the French Authorities, when they become available, will consider this further.

It is interesting to note that the recommendation in the EMA Guidance as well as similar 2006 recommendations of the French Medicines Agency (AFSSaPS) for allowing sufficient time gaps between dosing of healthy volunteers does not seem to have been followed. Dosing was planned to take place with just 10 minutes between subjects dosed on the same day. Bial has been criticised by French Authorities  as well as in an editorial of the British Journal of Clinical Pharmacology[3] for not planning sufficient time gaps between dosing of patients.

Regulatory response

The ANSM has already ordered that certain precautionary measure should apply from 31 March 2016 to all trials which it has authorised, including:

  • Trial suspension and fresh authorisations. Upon the occurrence of new facts/developments in trials involving healthy volunteers, the trial must be suspended immediately and fresh approvals from authorities must be obtained before resuming the trial.
  • Immediate reporting. The timeline for expedited reporting by a sponsor of a SUSAR is shortened from “as soon as possible” to “immediately” reporting obligation to authorities (with the longstop of 7 days unchanged)
  • Additional global reporting requirement. Any SUSAR occurring in any other trial anywhere in the world on a related compound, including those conducted by an affiliate company of the sponsor, must be reported by the sponsor immediately to ANSM
  • Fresh informed consent: upon the occurrence of new facts/developments in trials involving healthy volunteers, written informed consent must be obtained afresh from every participant before administering further doses to them.


  • While the trial was conducted in compliance with the letter of the law, it is clear that serious gaps are emerging from both a procedural and clinical viewpoint that require an urgent review of the clinical trials regime under both the Clinical Trials Directive and the Clinical Trials Regulation. Changes to French law and guidance have already been announced, and any sponsors or CROs conducting trials at sites in France will need to implement these changes immediately. Moreover, the EMA has indicated that the findings of the French Authorities could trigger such a revision to EU-wide guidance from the EMA on first-in-man trials. Revisions to the EMA guidance are likely to have global ramifications, as most jurisdictions seek to harmonise trial standards under the influence of the International Conference on Harmonisation of Technical Requirements for the Registration of Pharmaceuticals for Human Use (“ICH”). If the ANSM measures are indicative of this potential EU wide reform, changes can be expected in the areas of robustness of pharmacokinetic data, safety measures, screening criteria, reporting and participant consent for phase 1 trials in particular, but possibly for all trials as well.

[1] Pharmacokinetics is the branch of pharmacology concerned with the rate at which drugs are absorbed, distributed, metabolised and eliminated by the body (sometimes also described as what the body does to the drug).

[2] Pharmacodynamics is the branch of pharmacology that studies the effect and mode(s) of action of the drug upon the body.

[3] Br J Clin Pharmacol (2016) 81 582—586.