IN THIS ISSUE: REGULATORY ROUND UP

Special features Meeting report - 10thBrAPP Education Day

Personal Development -Developing ResilienceUsing Mindfulness atwork

JOURNAL OF THE BRITISHASSOCIATION OFPHARMACEUTICALPHYSICIANS

PHARMACEUTICAL PHYSICIAN

APRIL 2018 VOLUME 28 | SPRING

Resourcing Solutions for Medical Affairs, Pharmacovigilance and Clinical Development

Providing Pharmaceutical Physicians

www.axess.co.uk

This is just a selection of the current assignments with our pharmaceutical clients. For a confidential discussion please telephone Beth Thomas-Stonier at AXESS Limited on 020 8560 2300. To apply please send your CV to jobs@axess.co.uk quoting the reference number.Visit our website www.axess.co.uk to register for jobs by e-mail – new roles that match your criteria e-mailed to you on the same day that they are posted.

Permanent Roles

Medical Director EMEA – Nephrology Global Pharma – strategic launch role Surrey PP 6984

Associate Director, Country Medical Lead Haematology Global Biopharma – good portfolio and pipeline, team leadership London PP 7027

Associate Director, Country Medical Lead Genetic Disease Global Biopharma – good portfolio and pipeline, team leadership London PP 7021

Medical Manager Oncology UK Global Pharma – Launches Bucks PP 7053

Medical Manager Diabetes UK Global Pharma – interesting projects Bucks PP 7001

Medical Manager Neurology UK Global Biopharma – launch West London PP 6957

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Medical Advisor UK Speciality Pharma – entry level medic role Middlesex PP 6974

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Medical Advisor Haematology Global Biopharma – Launches Munich, Germany PP 7016

Medical Director Early Clinical Research Research Organisation – Respiratory/ Infectious Diseases Central London PP 6882

Principal Investigator – Early Clinical Research Research Organisation – Respiratory/ Infectious Diseases Central London PP 6951

Medical Monitor Emerging Biotech – Pivotal phase II / III EU clinical trials Central London PP 7054

PHARMACEUTICAL PHYSICIAN

Published 6 times per annum by BrAPPRoyal Station Court, Station RoadTwyford, Reading, Berkshire RG10 9NF. Telephone +44 (0)118 934 1943 Fax +44 (0)118 932 0981 Email info@brapp.org www.brapp.org

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The views expressed in the journal are those of the authors and may notcomply with the views of BrAPP or the authors' own companies.

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EDITORIAL BOARD: DR JANE BARRETT

DR HUGH BOARDMAN

DR DAVID FOWLER

LIZ LANGLEY LIZ@BRAPP.ORG

DESIGN: DANA KIDSON

DANA.KIDSON@GMAIL.COM

EDITORIAL 3

REGULATORY ROUND-UP 4Anne Hetherington

MEETING REPORT 810th BrAPP Education Day

Drs Rob Barden, CarlosCarrasco, Kamlesh Sheth, JoyChukwujindu

PERSONALDEVELOPMENT 19Developing Resilience

Using Mindfulness at workSharon Leighton and SueWeston

REVIEW 23Charisma Workshop

Dr Liz Clark

TRIBUTESDr Joe Chiesa 25

Dr Flic Gabbay and David Blowers

Peter Jay 27

Dr Jane Barrett

Contents

APRIL 2018 VOLUME 28 | SPRING

Senior Pharmaceutical Physicians and Scientists – UK, US

Push science further, develop innovative clinical programs, help patients moreAt AstraZeneca, we are committed to developing new therapies that bring life-changing medicines to more cancer patients.

We are motivated by a dedication to the scientific discovery, strategic clinical programs development and implementation that enable new oncology medicines reach the patients in need.

We seek collaboration with leading experts and institutions that will one-day help eliminate cancer as a cause of death.

We have a wealth of opportunities spanning early and late phase clinical programmes and medical affairs to enable us to drive forward one of the most exciting pipelines in the industry.

As part of our team, you’ll have ownership of the design, development and delivery of clinical trial programmes that will generate the data required to drive regulatory submissions for new medicines and expanded indications and provide the evidence that shows their true value.

If you’d relish the prospect of creating life-changing medicines in a dynamic, collaborative environment, find out more at www.careers.astrazeneca.com

April 2018

volume 28 | springPHARMACEUTICAL PHYSICIAN

3

WELCOME TO A Spring issue ofPharmaceutical Physician. We live ininteresting and changing times – theweather in the UK is but one exampleof this and we have experienced twoSSW events so far in 2018 – SuddenStratospheric Warming for the non-meteorologically minded amongst you.The first caused London (and yes, otherand most parts of the country weremuch more severely affected) to beplunged into a picturesque buttreacherous city and it even snowedinside (not around or blown in from theoutside) the canopy of PaddingtonStation such were the weird atmosphericconditions. Nevertheless the turnout forSession 2 of the PostGraduate Course inPharmaceutical Medicine was 100% andit is probably true that a degree ofadversity brings out the best in us. Theyare all to be congratulated for theirfortitude.

The direction of the April issue of PP isto continue the theme of improvementthrough experience and learning. Wehave two articles which may help eachand every one of us respond toworkplace challenges and feel moreinvolved and yet more content. SharonLeighton looks at developing resiliencethrough mindfulness. And Liz Clarkreports on attending a charismaworkshop where she was forced toreflect how we present ourselves in lifeand the benefits of thinking about howothers might receive those messages.

Tributes are also paid to twocontributors to the advancement ofpharmaceutical medicine. Dr Joe Chiesa,a familiar face at BrAPP and Facultymeetings and a doyen to the importanceof the training of pharmaceuticalphysicians is remembered by his mostrecent work colleagues at TranScripPartners and also by a friend and formercolleague, Dr David Blowers. Also, PeterJay could certainly be described as acharacter in our midst. The identificationand detection of clinical trial fraud is ofparamount importance to the industryand not least to patients. Peter as aretired senior policemen was very adept

at “smelling a rat”. Dr Jane Barrett whoworked closely with him offers herrecollections.

The bulk of this issue is a detailed andfascinating report of our 2017 BrAPPEducation Day. Drs Barden,Chukwujindu, Carrasco and Shethprovide their reflections on anothersuper day. It was also the occasionupon which BrAPP celebrated its 60thbirthday. A global landmark forassociations of doctors working in thepharmaceutical industry. Pictures of theday will soon be available on the newBrAPP website which will be launchedlater in April.

Change and development are inevitablefactors in life and at BrAPP we need torespond to the needs of our membersand their colleagues. For the foreseeablefuture, we plan to reduce the frequencyof Pharmaceutical Physician from six tofour times per year. Authors areincreasingly finding article creationchallenging. However, we also plan tocommunicate with you more frequentlyvia email and sometimes social media –we are currently reviewing our policy!The advent of GDPR (General DataProtection Regulation 2018) will requireus to continue to protect your data asbefore. Please be assured that we nevergive member or subscriber data to anyother person or organisation withoutexpress permission.

Communication and networking are ofgreat importance to us and we hope toyou too and so we are seeking ways toenhance our communication strategy. Ifyou have any thoughts or ideas as tohow we might do things better, pleasefeel free to get in touch.

April 2018

EDITORIAL

REGULATORY ROUND UP

By Anne Hetherington, Senior Regulatory Consultant, Envigo Ltd.

HERE IS THE LATEST ROUND UP OF REGULATORY NEWS FROM THE LEADING

AGENCIES, INCLUDING THE EUROPEAN MEDICINES AGENCY (EMA), THE MEDICINES

AND HEALTHCARE PRODUCTS REGULATORY AGENCY (MHRA) AND THE FOOD AND

DRUGS ADMINISTRATION (FDA). EMPHASIS IS PLACED ON THOSE NEW

REGULATIONS WHICH IMPACT ON CLINICAL AREAS.

PLEASE CLICK ON THE LINKS BELOW TO TAKE YOU TO THE RELEVANT ITEM.

WE HOPE THAT YOU WILL FIND THIS DIGEST OF INTEREST. IF YOU HAVE ANY

COMMENTS OR QUERIES PLEASE CONTACT US AT INFO@ENVIGO.CO.UK. ANNE

HETHERINGTON, SENIOR REGULATORY CONSULTANT

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4PHARMACEUTICAL PHYSICIAN

EUROPEAN MEDICINES AGENCY (EMA)

News and press releases• News and press releases: EMA’s

Business Continuity Plan for Brexitpublished

• News and press releases: Raisingawareness of the perils ofantimicrobial resistance

• News and press releases: EU scientificopinion: how to assess progress onreduction of antimicrobial resistanceand antimicrobial consumption

• News and press releases: Reportingside effects of medicines

• News and press releases: Unparalleledaccess to clinical data - one year on

• News and press releases: New actionplan to foster development ofadvanced therapies

• News and press releases: EMA takesyet another step in public engagementwith its first public hearing

Updates• Scientific guideline: Concept paper on

predictive biomarker-based assaydevelopment in the context of drugdevelopment and lifecycle, draft:consultation open

• Scientific guideline: Guideline onstrategies to identify and mitigate risksfor first-in-human and early clinicaltrials with investigational medicinalproducts - Revision 1, adopted

• Scientific guideline: Concept paper onthe revision of the guideline onquality, non-clinical and clinicalaspects of medicinal productscontaining genetically modified cells -Superseding document, draft:consultation open

• Scientific guideline: Reflection paperon promotion of pharmacovigilancereporting, adopted (updated)

• Scientific guideline: Draft ICH E9 (R1)addendum on Estimands andsensitivity analysis in clinical trials tothe guideline on statistical principles

Anne Hetherington

ENVIGO.COM

for clinical trials, step 2b - Revision 1,draft: consultation open

• Scientific guideline: Addendum to theguideline on the evaluation ofmedicinal products indicated fortreatment of bacterial infections toaddress the clinical development ofnew agents to treat pulmonary diseasedue to Mycobacterium tuberculosis -Revision 1, adopted

• Scientific guideline: Reflection paper onthe pharmaceutical development ofmedicines for use in the olderpopulation - First version, draft:consultation open

• Regulatory and procedural guideline:Guideline on good pharmacovigilancepractices (GVP) - Product- orpopulation-specific considerations IV:paediatric population, draft:consultation open

• Regulatory and procedural guideline:Comments received from publicconsultation on goodpharmacovigilance practices (GVP) -GVP Module VI – Management andreporting of adverse reactions tomedicinal products(EMA/873138/2011 Rev. 2)

• News and press releases: Science andinnovation for better medicines

• News and press releases: Involvingyoung people in EMA activities

• Newsletter: What's new inpharmacovigilance - QPPV Update -Issue 2 - 2017

• Regulatory and procedural guideline:External guidance on theimplementation of the EuropeanMedicines Agency policy on thepublication of clinical data formedicinal products for human use(version 1.3), adopted

• Scientific guideline: Guideline onclinical investigation of medicinalproducts for the treatment of chronic

heart failure - Revision 2, adopted

• Scientific guideline: Guideline onclinical investigation of new medicinalproducts for the treatment of acutecoronary syndrome - First version,adopted

• Scientific guideline: Guideline on theclinical investigation of medicinalproducts for the treatment of axialspondyloarthritis - Revision 1, adopted

• Scientific guideline: Draft guideline onthe clinical evaluation of medicinalproducts indicated for the prophylaxisor treatment of respiratory syncytialvirus (RSV) disease, draft: consultationopen

• Scientific guideline: Draft guideline onclinical investigation of recombinantand 4 human plasma-derived factorVIII products, draft: consultation open

• Scientific guideline: Reflection paper onthe use of extrapolation in thedevelopment of medicines forpaediatrics, draft: consultation open

• Scientific guideline: ICH guideline E18on genomic sampling andmanagement of genomic data - Firstversion, adopted

• Scientific guideline: Guideline on goodpharmacovigilance practices: ModuleXV – Safety communication (Rev. 1),adopted (updated)

• Scientific guideline: Guideline on goodpharmacovigilance practices (GVP) -Module VIII – Post-authorisation safetystudies (Rev. 3), adopted (updated)

• Scientific guideline: Guideline on goodpharmacovigilance practices: Annex I- Definitions (Rev. 4), adopted(updated)

• Scientific guideline: Guideline on goodpharmacovigilance practices (GVP):Module IX – Signal management (Rev.1), adopted

Overview of comments received on'Guideline on strategies to identify andmitigate risks for first-in-human andearly clinical trials with investigationalmedicinal products', adopted

Overview of comments received on draftGuideline on clinical investigation ofmedicinal products for the treatment ofchronic heart failure(CPMP/EWP/235/95, Rev.2)

Overview of comments received on'Guideline on clinical investigation ofnew medicinal products for thetreatment of acute coronary syndrome'

MEDICINES AND HEALTHCARE

PRODUCTS REGULATORY AGENCY

(MHRA)

• MHRA and making a success of Brexit

• BIA & MHRA publish report'Innovation in life sciences in achanging and dynamic environment’

FOOD AND DRUGS ADMINISTRATION

(FDA)

• FDA develops rapid and sensitive assayto assess antibody response to Ebolavirus vaccine without using the virus

REGULATORY ROUND UP

April 2018

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REGULATORY ROUND UP

PHARMACEUTICAL PHYSICIAN

• FDA approves Vabomere (meropenemand vaborbactama), a newantibacterial drug

• Antibacterial Therapies for PatientsWith an Unmet Medical Need for theTreatment of Serious BacterialDiseases

• FDA develops a novel biomarker basedtest that improves ability to identifyasymptomatic carriers of malaria

• FDARA: Making a Difference forIndustry and Patients

• FDA Press Release: FDA improvesaccess to reports of adverse drugreactions

• Expedited Programs for SeriousConditions––Drugs and BiologicsGuidance for Industry

• E9(R1) Statistical Principles forClinical Trials: Addendum: Estimandsand Sensitivity Analysis in ClinicalTrials Guidance for Industry

• Pediatric Gastroesophageal RefluxDisease: Developing Drugs forTreatment Guidance for Industry

• Respiratory Syncytial Virus Infection:Developing Antiviral Drugs forProphylaxis and Treatment Guidancefor Industry

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PHARMACEUTICAL PHYSICIAN CONTACT: Liz Langley

Info@brapp.org 0118 934 1943

Advertiseyourrecruitmentopportunitieshere or on theBrAPP website.

WHAT? The Patient Centred Outcomes (PCO) team at pH Associates are experienced in measuring treatment

benefit and impact of disease from a patient perspective.

pH Associates (www.phassociates.com) is an OPEN Health company (www.OPENhealth.co.uk).

WHY?

Delivering patient centred evidence from early drug development to late stage use is now a requirement

for all stakeholders.

To establish long-term successful medicines,

Work with us to measure how a patient is feeling and to understand the actual impact of treatment or

disease on daily life.

HOW? Our PCO consultants, with expertise in measuring the patient perspective, partner with our clients to:

1. Optimise patient centred measurement strategy.

2. Collect the right patient centred data at the right time.

3. Turn data into patient centred value messages.

Power to the

Patient

Dr Angela Rylands T: +44 1628 897888

E: Angelarylands@phassociates.com

Dr Catherine Bottomley T: +44 1628 481112

E: Catherinebottomley@phassociates.com

MEETING REPORT:BrAPP Education Day: 05 December 2017

Report by Drs Rob Barden, Carlos Carrasco, Kamlesh Sheth and Joy Chukwujindu

THE 10TH BRAPP EDUCATION DAY

OFFERED MEMBERS AND COLLEAGUES

AN INSIGHT INTO SOME OF THE MOST

EXCITING DEVELOPMENTS IN GENE

THERAPY AS WELL UPDATES ON

REGULATORY, COMPLIANCE AND

SAFETY ISSUES

April 2018

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8PHARMACEUTICAL PHYSICIAN

CAR T-CELL THERAPY INHAEMATOLOGICALMALIGNANCIESProfessor David Linch,

Professor of Haematology, UCL

Professor David Linch gave a verycomprehensive and insightfulpresentation on this exciting andcomplex state-of-the-art therapy.

He set the scene by stating that therewas still a considerable ‘unmet clinicalneed’ even in the treatment of

relatively good risk malignancies suchas Acute lymphoblastic leukaemia(ALL) and Diffuse large B-celllymphoma (DLBCL), with survivalbeing considerably reduced the laterthe age at onset. In children andyoung adults, even though the 5yrsurvival is high, post relapse resultsare poor. Also many patients aredeemed unsuitable for transplantationdue to uncontrolled disease, withsurvival post-transplant relapse beingvery poor.

Caption: Coloured scanning electron micrograph (SEM) of a cancer cell (green)

being attacked by a chimeric antigen receptor (CAR) T-cell (pink). The breast

cancer cell is undergoing programmed cell death, or apoptosis, which has been

induced by the CAR T-cell. CAR T-cells are cells from a patient's immune system

that have been extracted and modified to recognise and attack the patient's

cancer cells, before being reintroduced to the patient. Magnification: x3,660

when printed at 10 centimetres wide.

Credit: EYE OF SCIENCE/SCIENCE PHOTO LIBRARY

Treatment of haematologicalmalignancies involving the immunesystem using T-cell directed depletioncommenced in 1956 with Barnes andLoutit’s mouse model concept of ‘graftversus leukaemia’ and has since evolvedinto the contemporary geneticengineering of T-cells initially involvingthe creation of new T-cell specificitiessuch as T-cell receptors (TCRs) andmore recently Chimeric antigenreceptors (CARs) using ‘Adaptive CellTransfer’ technology, with the 3 keysuccess factors being related to CAR T-cell production, Vector anatomy andLymphodepletion.

CARs are engineered receptors whichare derived from monoclonalantibodies. They consist of 2 maincomponents – an intracellular TCRsignalling component (Endodomain)which is the functional end of thereceptor and an extracellular antigenrecognition region, often antibodyderived from immunoglobulin chains,(Ectodomain), this being the recognitionend of the receptor. They are linkedthrough the cell membrane(Transmembrane domain).

The extracellular antigen recognitionregion targets and binds onto specifictumour associated antigens, the onemost commonly targeted to date beingthe CD19 antigen, which are found onmalignant B-cells (and also healthycells).

1st generation CARs had a relativelysimple intracellular domain fromendogenous TCRs (CD3-zeta chain),with little evidence of anti-tumouractivity. 2nd generation CARs possess anadditional costimulatory domain (e.g.CD28), thereby providing additionalsignals to the T cell, with 3rd generationCARs progressing to possess 2costimulatory domains (e.g. CD28 +OX40), to further augment potency andto improve their expansion andpersistence. [See Figure: TheDevelopment of CARs]

The art of CAR T-cell production isshrouded in secrecy, but essentiallystarts with the removal of white cellsfrom the patient by leukapheresis,which are then taken to a specialistproduction facility where the T-cells areactivated and genetically engineered.

Currently this is most often facilitated byusing a viral vector (e.g. retrovirus) totransfer the coding sequence, so that itis expressed in CARs which arespecifically directed towards antigens onthe patient’s own tumour cells. Thesegenetically engineered CAR T-cells arethen expanded under various conditionsand harvested. Finally, they are re-infused into the patient, who will haveundergone a preparativelymphodepletion prior to the re-infusion. This whole process can takearound 17 days. [See Figure: AdoptiveImmunotherapy with Engineered T-cells].

There is a need to lymphodeplete thepatient prior to reinfusion of thegenetically modified CAR T-cells. This iscommonly achieved with fludarabineand cyclophosphamide.

Most early studies resulted in poorpersistence of the infused CAR T-cells,showing only transient efficacy, butminimal toxicity, aside from the need tomanage the depletion of normal B-cells.However more recent studies using 2ndand 3rd generation CARs, mainly inpatients with ALL and DLBCL, haveshown much improved overall responserates (Partial response + Complete

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Continues on page 10 ��

9

| FIGURE 1: Adoptive Immunotherapy with Engineered T-cells

T-cells extracted

Blood sample

T-cells engineered

Administered back to patient

ModifiedT-cells

recognize and kill

tumour

Kershaw MH et al; Nat Rev Immunol. 2005 Dec;5(12):928‐40.Kershaw MH et al; Nat Rev Cancer. 2013 Aug; 13(8):525‐541

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PHARMACEUTICAL PHYSICIAN

response), with increasing relapse freesurvival. But as these cells are notcleared from the body quickly, as wellas causing normal-cell depletion, theyoften show characteristics such ascytokine release syndrome (CRS) earlyon or neurotoxicity such asencephalopathy. CRS is currently treatedwith short course steroids (but thesemay compromise the persistence of theCAR T-cells) and IL-6R antagonismusing tocilizumab. One furtherpossibility to is to engineer a ‘suicidegene’ into the modified CAR T-cells.

The FDA have recently approved thefirst two CD19 targeted CAR therapies.Kymriah (tisagenlesleucal; Novartis) isnow licensed in the US for use inrelapsing/refractory B-cell precursor ALLand Yescarta (axicabtagene ciloleucel;Kite/Gilead) for use inrelapsing/refractory DLBLC.

Prof Linch mentioned the 4th Hurdlechallenges ahead for both products inrespect of their gaining NICE approval,given their respective high cost ofgoods, even at a QALY threshold of£50k.

He closed by stating that CAR T-celltherapy was still only in its infancy andthat today it is only used in end-stagepatients, but posed the question –“What of tomorrow?”

CURRENT TRENDS IN CANCERIMMUNOTHERAPYSpeaker: Mike Holmes MD FRCS

Overview:Advances in immunotherapies forcancer have propagated new treatmentsthat trigger the immune system toeffectively respond and attack tumours,delivering dramatic benefits to patientswho suffer with cancer. Dr MikeHolmes MD FRCS, Executive Director ofOncology for Medical Affairs in Europeand Canada, MSD - presented afascinating historical timeline on how acentury (1890-1990) of immunologicalresearch into cancer was marginalisedand blatantly ignored by the scientificcommunity. Regardless of various

seminal immunological advances,immunotherapy, as a means towardstreating cancer failed to flourish andgain any momentum. Mike summarisedand collated key stories from severalinvestigators who performed theseground-breaking experiments andestablished the frontiers of cancerimmunotherapy. Today more recentimmunological breakthroughs havecatapulted this once ostracised scienceinto the limelight generating amomentous surge and shift towards thepremise that this therapy – could just be– the beginning of the end of cancer.These are exciting times for cancerimmunotherapy. After many years ofdisappointing results, the tide has finallychanged and immunotherapy hasbecome a clinically validated treatmentfor many cancers and otherautoimmune diseases. Mike thenpresented how such key immunologicaldiscoveries led to the generation andlaunch of new medicines unleashing theimmune system’s ability to attacktumours and halt the spread of cancer.

Toxic bacteria, magic bullets, cancer

immunity cycle to the global

pharmaceutical manufacturing of

CTLA-4 and PD-1/L1: Immunological

Evolution to Revolution of Cancer

Treatments.

Coley’s Toxin and Ehrlich’s ‘magic bulletconcept’Mike initiated his presentation byintroducing and conveying thecaptivating life story of the widelyregarded “father of immunotherapy” –William B. Coley (1862-1936). In the1890s, this bold clinician-scientistplunged a syringe loaded with livingStreptococcus pyogenes into aninoperable obstructive tumour at thebase of a drug addict’s neck – simplyon a hunch that severe infection couldcause cancer to regress. His hunch wasbased off of 47 scant patient profilesand an obsession into one particularcase, according to the medical literature,that found this doctor franticallyscouring the ghettos in New York citywhere an alleged German immigrant,who seven years prior with terminal

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cancer, had been found cancer-freesolely after contracting a widespreaderythematous superficial skin infection,i.e. erysipelas, caused by beta-hemolyticgroup A Streptococcus bacteria. Mikestressed to the audience that was allColey needed to proceed directly tohuman trials, and the infamous drugaddict named Zola would become hisfirst test subject.

Advancing twenty years past this initialevent (i.e. 1910), Mike then went on todescribe Paul Ehrlich's, German NobelLaureate and ‘founder of chemotherapy’(1854-1915), ‘magic bullet concept’which postulates the ability to engineerand create ‘targeted cell-structure based-medical therapies’ to attack pathogens;whilst, remaining harmless withinhealthy tissues. Ehrlich was able to basesuch theories on his beliefs and was thefirst to coin the phrase ‘receptors’. Hebelieved that these so-called ‘receptors’bound and had affinity towardsantigens. Moreover he hypothesized thatthese receptors are either associatedwith cells or were dispersed widelythroughout the blood stream inresponse to antigen interactions.Ironically, all of these beliefs were built

upon his experiences in the treatment ofinfectious diseases with drugs derivedfrom the German dye industry. Thuschemical dyes were the catalyst andfoundation for early chemotherapyusage in man.

The Cancer Immunity CycleAs surgical resection, chemo- andradiotherapy gradually evolved tobecome the cornerstone and maintreatments for cancer management;further elucidation into thepathophysiology of cancer immunityand T cell biology progressed, albeit inseparate and divergent paths. Mike nextfocused his presentation on the sevenpathophysiological steps that cancerutilises to evade the escape of theimmune system.

1. Release of cancer cell antigens(cancer cell death)

2. Cancer antigen presentation

3. Priming and activation of T cells

4. Trafficking of T cells to tumours

5. Infiltration of T cells into tumours

6. Recognition of cancer cells by T cells

7. Eventual killing or destruction of thecancer cells. Reviewed in: Chen and Mellman Imm.

Rev 2013

Mike explained that the cancer immunecycle and its cellular interactions arecomplex. Nevertheless, he described thesteps of the cycle (i.e. key immune cellsand key effective molecules) in a clearand comprehensive fashion. Moreover,he stressed that ongoing research andclinical trials are advancing ourknowledge into the molecular andcellular intricacies that encompasscancer medicine. This knowledge hassupported principal investigators byidentifying crucial targets/checkpointssuch as CTLA-4 and PD-1/L1. Tumoursselectively express CTLA-4 in peripherallymph node tissue, whilst PD-1 isexpressed in a variety of immune cells.Biologics, monoclonal antibodies, withan affinity towards these immuneregulators have shown theireffectiveness at disrupting a cancer cell’sability to evade immune surveillanceallowing patients the ability to mount aneffective immune response. Inhibition ofeither CTLA-4 or PD-1/L1 hasculminated in the pharmaceutical

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| FIGURE 2: The Cancer Immunity Cycle

Killing of cancer cellsAnti-PD-L1Anti-PD-1IDO inhibitors

Release of cancer cell antigensChemotherapyRadiation therapyTergeted therapy

Cancer antigenpresentationVaccinesIFN-αGM-CSFAnti-CD40 (agonist)TLR agonists

Recognition of cancer cells by T cells CARs

Trafficking of T cells to tumorsPriming and Activation

VaccinesAnti-CTLA4Anti-CD137 (agonist)Anti-OX40 (agonist)Anti CD27 (agonist)IL-2IL-12

Infiltration of T cells into tumorsAnti-VEGF

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PHARMACEUTICAL PHYSICIAN

manufacture and administration of theseimmunotherapies for melanoma,non–small cell lung cancer (NSCLC),and other cancers.

Mike indicated that CTLA-4 was the firstimmune checkpoint receptor to beclinically targeted. Ipilimumab (Bristol-Myers Squibb, Princeton, NJ), aninhibitor of CTLA-4, is approved for thetreatment of advanced or unresectablemelanoma. He presented Ipilimumab’simpactful pooled survival analysis fromPhase II/III trials in advanced melanoma.He then conveyed that hundreds ofclinical trials on anti-PD-1/L1 mAbs areunder active development. Some of themhave entered phase 3 clinical trials andare benefiting many patients.Pembrolizumab (Keytruda® injection,MSD) is a high-affinity, humanized IgG4PD-1 blocking antibody approved by theFDA and the EU is licensed for renal cellcarcinoma, NSCLC, HNSCC (head andneck squamous cell carcinoma) andbladder (urothelial) cancer.

Mike summarised his presentation withthe future developments in cancerimmunotherapy.

• Re-exploring therapeutic limits –combination strategies ( > 80 underinvestigation)

• Novel immune checkpoint targets andmodulators (T cell has > 200 receptortypes)

• New biomarkers to help targettherapies

• CAR-T cell therapy

• Bispecific antibodies

• Individualisation in mouse xenografts

• Blood based biopsies includingcfDNA singatures

EARLY ACCESS TO MEDICINES(EAMS) SCHEME Dr Zahid Bashir of Omniac Pharm

Consult Ltd

Industry has made great progress inmaking life-saving treatments availablefor several hundreds of conditions.However there remain numerous life-threatening and chronically debilitatingconditions for which there are no

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THERE REMAIN NUMEROUS LIFE-THREATENING AND CHRONICALLY

DEBILITATING CONDITIONS FOR WHICH THERE ARE NO LICENSED TREATMENTS

AVAILABLE.

licensed treatments available. There aremany compounds in the Industry’spipeline, some of them with greatpotential, to address this unmet need.The issue is; patients with life-threatening conditions don’t have time towait for these compounds to completethe full clinical development andregulatory processes before being madeavailable by regular access channels.

One way to access these promisingunlicensed medicines is by participatingin clinical trials; however not all patientsare eligible for ongoing clinical trials.They access unlicensed medicines bymechanisms known by a plethora ofterms – managed access programmes,early access, expanded access, namedpatient use, and compassionate use.Confusing?

Dr Zahid Bashir of Omniac PharmConsult Ltd cleared the confusion in hisvery engaging lecture on his experienceof Early Access to Medicines (EAMS)scheme in the UK at the recent BrAPPeducation day. Use of prescription-onlymedicines prior to grant of marketingauthorisation by competent authorities is

known as unlicensed medicine use. Thelegal basis of such a use is Article 5Directive 2001/83 EC, for an individualpatient and article 83 Regulation726/2004/EC for cohort of patients.Different member states haveimplemented this differently and so far,France was the only state to havesuccessfully implemented successfulcohort access to unlicensed medicines –ATU.

In the UK, EAMS was launched in April2014 with the aim to give patients withlife-threatening or seriously debilitatingconditions access to medicines that donot yet have marketing authorisationwhen there is a clear unmet medicalneed. Dr Bashir explained that EAMS isnot a substitute for appropriate clinicaldevelopment and is primarily aimed atmedicines towards the end of theirdevelopment

There are four main stakeholders in thefive-step EAMS process (Fig 3. - belowand Fig 4. - page 14). The first step isPromising Innovative Medicinedesignation, which is generally based onphase II or phase III data.

Once the PIM designation is obtained,the company can ask for a pre-submission meeting with MHRA andapply for the next step i.e. scientificopinion. The EAMS dossier follows theCommon Technical Dossier (CTD)format. MHRA has a 75 -90 day processand issues a scientific opinion (SO)taking into consideration thebenefit:risk. This opinion is valid for oneyear and the company can apply forrenewal. Whilst PIM decisions are notpublicised by MHRA, the SO arepublished on the MHRA website.

The next step is implementation incollaboration with NHS England and thecompany needs to make the drugavailable free of charge until theMarketing Authorisation is granted. Thisis different from the French ATUprogramme where the ATU drugs arereimbursed. This is one of the potentialdownsides of the scheme forpharmaceutical companies. However,there are indeed several advantages forthe companies: creating goodwillamongst health professionals andpatients by making innovative medicinesfor conditions with real unmet medicalneed, opportunities for data collectionfor NICE submission. In addition, thebaseline commissioning for EAMS

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| FIGURE 3: The EAMS process (1)

PHARMA MHRA

NHS

EAMS- A Collaborative Effort

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medicines (following positive NICEguidance) is reduced to 30 days (usually3 months).

Dr Bashir emphasised the importance ofhaving a clear exit strategy for thecompanies especially in cases where theNICE decision is negative.

In summary, this was a truly engaginglecture by Dr Bashir who shared hisexperience of the UK EAMS andclarified the process as well as pros andcons of EAMS.

SETTING THE STANDARDSFOR THE PROMOTION OFMEDICINESEtta Logan,

Deputy Director PMCPA

Etta gave yet another useful topicalpresentation in relation to PMCPAactivities, majoring on the PMCPA’sfindings from audits entitled ‘Learningfrom audits’.

Learning from audits:Etta set the scene by pointing out that 3audits had already been arranged for2018, suggesting that they appeared tobe coming more prevalent!

Audits are usually requested by eitherthe Code of Practice Appeal Board as aCode ruling sanction or by the ABPIBoard to assist in deciding whether tosuspend or expel a company from theABPI. A company may also request avoluntary audit!

For those of who have not had thedubious pleasure of participating in aPMCPA Audit, Etta started by outliningthe procedure. This starts with theAuthority requesting that the companyprovides them with certain materials forexamination prior to their visit - theseoften include specific items which wereassociated with the circumstances whichgave rise to the audit. The Authorityaudit team normally consists of 2-3members. A list of individuals requiredto attend for confidential interviews(including staff from European HQs) isdrawn up by the audit team. Therequested materials are examined indepth. Company procedures arereviewed and discussed. The visit maylast 2-3 days, with a report withrecommendations being sent to thecompany shortly after the visit. Thecompany comments on the report,usually be specifying how it will

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| FIGURE 4: The EAMS process (2)

EAMS

MHRA

Review and approval of PIM and EAMS

PHARMA Submissions

Provision of free of charge product during the EAMS period

HTA Bodies Advice regarding data collection

Prioritization of HTA review

NHS Implementation at hospital level Communication to NHS providers, doctors and pharmacists

actively address the Authority’srecommendations, the objective being toavoid the Appeal Board requesting theneed for a re-audit!

So what are the major learnings?[See panel: Audits – Learning topics]

Leadership comes from the top,including the Board & CFO.

Have a company culture whichencourages staff to be responsible &accountable, also it operates in atransparent environment which activelyencourages debate.

Share Good Compliance Practice – veryimportant.Actively incorporate the commercialdivision into the company complianceinfrastructure, potentially by them beinginvolved with setting complianceobjectives and also placing them inSignatory roles.

Medical reviewers/signatories shouldhave sufficient standing within thecompany and also develop a soundprofessional relationship withcommercial colleagues, ideally built on

mutual respect for each other’s rolesand associated responsibilities.

Company Code Procedures SOPs shouldbe readily accessible, with staff beingregularly trained on them, such that theyhave an adequate up to date workingknowledge of them, which will enablethem to carry out their role in a fullycode compliant way.

Code practices within the companyshould be carefully monitored to identifyareas of non-compliance and also errorsof process or decision-making, with alearnings system in place.

Simple solutions, such as Signatoriesmonitoring each other, may providecompliance alignment checks.

In respect of compliance psychology,this should enable the company to dobusiness more compliantly, ofteninvolving management getting to knowtheir staff, with the individual ultimatelyseeing compliance as a personalchallenge.

Financial controls relate to ensuring thatthe annual PMCPA ‘Disclosure’ detailsare complete and correct, particularly inrelation to ‘Transfer of Value’ returns.

Compliance risks may originate from‘Whistleblowers’ and also from notcarrying out due diligence on 3rd partieson appointment and thereafter notmanaging their use of subcontractorsand control of materials. Measuresshould be in place to manage knowncompliance risks.

Case Reviews published 2017 - PI safetyupdate issue:Etta pointed out that reviewers &Signatories should be particularlyvigilant in checking that the PI had beenupdated to reflect any safety-relatedupdates contained within the Summaryof Product Characteristics.

What else is PMCPA up to?:Etta informed us that they are workingwith the ‘Compliance Network’ on a

new guidance document relating to theapproval of meetings/meetingarrangements for meetings held outsidethe UK. They are also updating theirguidances relating to Clause 3 andDigital communications.

PHARMACOVIGILANCECURRENT THINKINGDr Kristina Strutt

Adverse drug reaction (ADR) definitioncovers both authorised use of amedicinal product and its use outside ofthe terms of the marketing authorisation.It is a response to a medicinal productwhich is noxious and unintended andmay arise from use of the productwithin or outside the terms of themarketing authorisation or fromoccupational exposure. Use outside themarketing authorisation includes off-label use, overdose, misuse, abuse andmedication errors. Off-label use:situations where the medicinal productis intentionally used for a medicalpurpose not in accordance with theterms of the marketing authorisation.Misuse: situations where the medicinalproduct is intentionally andinappropriately used not in accordancewith the terms of the marketingauthorisation. In practice there are

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| AUDITS - learning topics

Leadership

Company culture

Good Compliance Practice

Commercial engagement

Medical aspects

Company Code Procedures SOPs

Training

Monitoring

Simple solutions

Compliance psychology

Financial controls

Compliance risks

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challenges with identifying, coding andassessing 'special situations' reports forexample determining when aprescriber's action is intentional or not.

Expedited reporting: All suspectedADRs will now be submittedelectronically to EudraVigilance only.Serious ADRs to be submitted within 15days; Non-serious ADRs (EU only)within 90 days; fully functionalEudraVigilance went live on 22ndNovember 2017.

Signal detection & risk identification:

a signal is information arising from oneor multiple sources, includingobservations and experiments, whichsuggests a new potentially causalassociation, or a new aspect of a knownassociation between an intervention andan event or set of related events, eitheradverse or beneficial, that is judged tobe of sufficient likelihood to justifyverificatory action. Signal detection isthe process of looking for and/oridentifying signals using data from anysource. For the purpose of monitoringdata in the EudraVigilance database,only signals related to an adversereaction shall be considered.

MAH is required to monitorEudraVigilance data as part of globalsignal detection activities. MAH isrequired to inform competentauthorities if new risks or changed risksor changes to risk benefit balancehave been detected.

The requirement for MAH to monitorEudraVigilance data and inform theAgency and national competentauthorities of validated signals will enterinto force on 22 February 2018 and willonly apply, for a transition period, toactive substances contained in medicinalproducts included in the ‘List ofmedicinal products under additionalmonitoring’ in force as of 22 November2017.

Signal validation is the process ofevaluating the data supporting thedetected signal in order to verify that

the available documentation containssufficient evidence demonstrating theexistence of a new potentially causalassociation, or a new aspect of a knownassociation, and therefore justifiesfurther analysis of the signal; thisevaluation should take into account thestrength of the evidence, the clinicalrelevance and the previous awarenessof the association.(Fig. 5)

Risk management plans: GVP Module V– Risk management systems (Rev 2)- 31 March2017: Revision 2 is a major revisionwith modifications throughout andcontains the following: furtherclarification of what RMPs should focuson in relation to an important identifiedor important potential risk and missinginformation; further guidance on theexpected changes in the RMP during thelife cycle of the product; updatedrequirements for different types of initialmarketing authorisation applications,with the aim to create risk-proportionateRMPs e.g. 'abbreviated' RMPs forgeneric products. Revised RMPtemplate is mandatory from 31st March2018. Where post-authorisation safetystudies and/or post-authorisationefficacy studies are a condition of themarketing authorisation, these studiesare to be included in the riskmanagement plan.

The RMP is a dynamic document thatshould be updated throughout the lifecycle of a product. This includes theaddition of safety concerns whererequired, but also, as the safety profileis further characterised, the removal orreclassification of safety concerns. Theaim of a RMP is to document the riskmanagement system considerednecessary to identify, characterise andminimise a medicinal product’simportant risks. The RMP should focuson the important identified risks,important potential risks and missinginformation. Important identified risksare likely to have an impact on therisk-benefit balance of the product andto be included in the RMP wouldusually warrant (1) further evaluation aspart of the pharmacovigilance plan (e.g.

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to investigate frequency, severity,seriousness and outcome of this riskunder normal conditions of use, whichpopulations are particularly at risk); (2)risk minimisation activities: productinformation advising on specific clinicalactions to be taken to minimise the riskor additional risk minimisation activities.The important potential risks to beincluded in the RMP are thoseimportant potential risks that, whenfurther characterised and if confirmed,would have an impact on the risk-benefit balance of the medicinalproduct.

Effectiveness of Risk Minimisation (GVPModule XV1 (Rev 2): MAH to monitor theoutcome of risk minimisation measuresfor each medicinal product; MAH to actupon findings: update risk managementsystem, monitor pharmacovigilance data,determine whether there are new risksand/or existing risks have changed orthere are changes to the benefit-riskprofile.

Evaluating the effectiveness of additionalrisk minimisation measures is necessaryto establish whether an intervention hasbeen effective or not, and if not why andwhich corrective actions are necessary.The evaluation should be performed forthe additional risk minimisation tools

individually and for the risk minimisationprogramme as a whole.Additional monitoring GVP Module X:Medicinal products readily identifiableby an inverted equilateral black triangle� are subject to additional monitoring.The triangle will be followed by anexplanatory statement in the summaryof product characteristics (SmPC) asfollows: “This medicinal product issubject to additional monitoring. Thiswill allow quick identification of newsafety information. Healthcareprofessionals are asked to report anysuspected adverse reactions. See section4.8 for how to report adversereactions.”

PBRER (PSUR) - GVP Module VII (Rev 1)The required format and content ofPSURs in the EU are based on those forthe Periodic Benefit Risk EvaluationReport (PBRER) described in the ICH-E2C(R2). The PBRER format replacesthe PSUR format previously described inthe ICH-E2C(R1). In line with the EUlegislation, the report is described asPSUR in the GVP Modules. In otherwords PBRER is called PSUR in the EU.The required format includes anexecutive summary followed by 19sections then Appendices. PBRER is amultifunctional document withcontributions from functions other than

Safety.

Pharmacovigilance System Master File - GVPModule II (Rev 2)The PSMF is located either at the site inthe EU where the mainpharmacovigilance activities of themarketing authorisation holder areperformed or at the site in the EUwhere the qualified person responsiblefor pharmacovigilance operates. Itshould be permanently available for

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| FIGURE 5: Possible decisions during the signal evaluation process

YES YES

NO

Signal validation Signal validatedFurther assessment

considering allavailable data

New or changedrisk?

Non-validated signal Refuted signal

Propose actions such as changes to

the productinformation and/or

other riskminimisation

measures

NO

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inspection and provided within 7 daysupon request from a competentauthority. The content includes list ofmedicinal products (with authorisationdetails), EU QPPV (qualifications,responsibilities, contact details), localcontact person(s), organisation structure& list of sites where variouspharmacovigilance activities areundertaken, computerised system &databases, description ofpharmacovigilance processes, qualitysystem (SOPs, resource management,documentation and location of records,incl. training, audit findings), annexes.

Safety Reporting under an IND: describesFDA expectations for a systematic dataassessment program as part of INDstudies which includes the compositionand role of a safety assessmentcommittee; aggregate analyses for

comparison of adverse event ratesacross treatment groups (sponsorsshould periodically review accumulatingsafety data collected across multiplestudies) and others.

EU Clinical Trials Regulation: comes intoapplication in 2019; includesinformation on unblinding treatmentallocation; unblinded information shallbe accessible only to persons who needto be involved in the safety reporting tothe Agency, to Data Safety MonitoringBoards ('DSMB'), or to personsperforming ongoing safety evaluationsduring the clinical trial.”

BrAPP is most grateful to its speakers fortheir time and involvement: Prof DavidLinch, Dr Mike Holmes, Dr ZahidBashir, Etta Logan and Dr KristinaStrutt

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PHARMACEUTICAL PHYSICIAN CONTACT: Liz Langley

Info@brapp.org 0118 934 1943

Advertise here or on the BrAPP website.

Reachyour target

market

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PERSONAL DEVELOPMENT:Developing Resilience: Using Mindfulness At Work

By Sharon Leighton, Sharon Leighton Consultancy Ltd in conjunction with Sue Weston, Relaxing the Mind

Sharon Leighton

19

LIFE IN THE workplace can be tough.Workloads increase, driving us to beobsessive about our productivity –there’s no hiding from dashboards andmetrics. Many of us work in virtualteams, isolated from the socialcompanionship of colleagues.Organisational change is a constant –new team structures, new roles,increased responsibility, and new tools.

Our job security is long gone: where weworried about the impact ofoutsourcing, now we feel threatened bybots and artificial intelligence. Anddon't get me started about thedistractions of social media, emails,instant messaging or the “crack cocaine”commonly know as Candy Crush andother casual games!

So how do we cope with theseeveryday stresses of our modernworking lives?

How can we develop emotionalresilience, keep our focus and stayhealthy (physically and mentally)?

Many of you would have read or heardabout Mindfulness. It’s reach is evergrowing. Many of your children mayhave learnt how to meditate at school oryour employer may offer in-house orexternal courses. They know it hasproven effects particularly on our mentalhealth: it reduces anxiety and depression,helps improve our attentiveness anddevelops emotional resilience. Morecrudely put, less distraction and morefocus = more work + less stress = lesssick days and lost productivity.

But there are also misconceptions aboutmindfulness. It’s not about using

colouring books to take our minds offour problems, going for a walk orsavoring the moment. It’s more aboutbeing mindful with what is happeningright here, right now. Some of you mayalready be familiar with whatmindfulness is and the evidence1 thatregularly practicing mindfulness canbring you multiple benefits in yourworkplace. Dr John Kabat Zinn, whobrought the practice of mindfulness tothe Western world, has describedmindfulness as

“awareness that arises through apyingattention, on purpose, in the presentmoment, non-judgementally. It’s aboutknowing what is on your mind”

In brief, mindfulness, as practiced in theWest, combines 3 practices: meditation+ relaxation techniques + a movementcomponent, like yoga, T’ai Chi orqigong (which I use myself).

In this article I’ll explore the relevanceof mindfulness at work in more depthand give you 5 tips you can try outtoday to develop emotional resilience,much needed in our busy lives. I’vealready shared my personal journey,including my initial resistance tomeditation in a blog post 2. Although Ifirst used the techniques to help mecope with a painful divorce, I foundcollateral benefits in helping me managemy stressful workload. Running yourown consultancy and training businesscan be a relentless slog!

BRINGING MINDFULNESSTECHNIQUES INTO YOURDAILY LIFEWith the long break over Christmas/NewYear, you may have made resolutions for

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2018. Maybe you wanted to addressyour harmful habits (unhealthy eating,consistent late working, social mediaaddiction, alcohol intake, etc). On amore positive note, maybe you wantedto focus on more constructive habits likemore sleep, physical exercise away fromyour desk or having fun.

So how are they going, now we’re inApril?

Like throwing mud at a wall, hopefullysome of it has stuck! Yet 60-80% ofpeople cannot keep to their intentions,with complex reasons why we struggleto maintain our resolutions. Mindfulnesspractice includes techniques to help usexamine, practice and stick to ourintentions. Through practicingmindfulness, especially meditation, wetrain ourselves to stop and pause in themoment. We ask ourselves a few vitalquestions.

“How am I reacting right now? Whatemotions are passing through me?”

“Where am I holding these emotions inmy body?”

Identifying these emotions and theirembodied manifestations can help stop

us in our tracks on the path ofbehavioural sabotage, allowing us toalter course towards a more desireddestination.

MANAGING MEETINGSLet’s take an example to show howmindfulness is relevant at work. I’msure attending or running meetings area significant part of your day. Yet howmany of you can truthfully say that youwere fully present for the wholemeeting?

By present, I mean engaged, listeningwith your full attention and completelyclear at the end how it is relevant toyou and what you need to do. I confessI’ve had days when I’m guilty ofdistracted thoughts, preoccupation withanother topic or lost to daydreaming (ormore likely a waking nightmare of howI’m going to meet multiple tightdeadlines).

We may be feeling impatient, frustratedby long-winded discussion with noconclusion or outcomes. Thisimpatience may have a mixture ofanxiety about the “wasted” time +irritation at the inefficient meetingprocess + boredom at going oversomething you know already.

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“How am I reacting rightnow? What emotions arepassing through me?”

“Where am I holding theseemotions in my body?”

Regular meditation trains our minds tolet go of our ever-present thoughts, niceor nasty, as they move through ourconsciousness. We learn to stand backand observe what’s going on. Weconsider how these emotions aremanifested in our bodies. This mentalpause allows us to get back to a moreimpartial, balanced state of being: inbody and mind.

Let’s backtrack and take a mindfulpause to re-examine that meetingsituation. We can use the 2 questionsabove to help us recognise thesefeelings of impatience, irritation andfrustration. We might notice that wehave a tightened jaw, hunchedshoulders, we’re fidgeting in our chairand have a slumped posture. Bypausing, we can bring our attentionback to the ongoing events. In tandem,we can consciously relax our jaw, sitmore upright in our chair and relax ourshoulders down. Then we are ready tolisten or interject, summarise thediscussion so far and consider if we areready to make a decision. Byrefocusing our attention, we come fromthe right mind state (alert but relaxed)with a powerful body posture andlanguage of attention and equanimity.Even in a virtual meeting where no-onecan see you, your emotional state andbody posture will be evident in yourvoice.

We can use these two potent questionsin many situations at work. A difficult ortedious meeting. A crucial conversation,where the stakes are high and theatmosphere charged with tension.Taking time out to pause and raise yourawareness of what lies beneath is apowerful technique, essential inleadership or management roles.

WHAT GIFT DO YOU BRINGTO OTHERS THROUGH YOURPRESENCE?Have you ever been around someonewho is predominantly negative, grumpyor picky, finding fault no matter howsmall? This can be very draining andunproductive, especially if you are that

person!

As the best teams have a range ofpersonality types and a diversity ofattitudes, there are always times whenpeople can clash. How do you dealwith this if you’re struggling to get alongwith someone? Commonly know as“your opportunity to practice” to thoseof us who follow mindfulness!

Avoidance is one strategy but if you arein a small, close-knit team that’s notrealistic. Instead of expecting others toshift in their way of behaving, you can“shift” yourself! Bring an attitude ofnatural curiosity and compassion forothers to the situation.

Aim to be impartial and use enquiry.What do you think is going on for themin their view of the world? Can yougently probe how they are viewing asituation? Many of us carry theemotional baggage of events that havehappened to us in the past – thoseinvisible scars. Learn to listen andunderstand more, judge less. From myown personal experience, I have foundthat barriers between me and peopleI’ve avoided in the past have fallenaway, allowing me to see the good inthem. Doesn't that sound like a qualityany leader needs to cultivate?

So let’s flip this argument. When youare at work (or at home), what attitude& energy do you predominantly display?What gifts do you bring to others? Self-awareness is a core competency for anyaspiring professional or leader. So if youdon’t know, why not ask others aroundyou who know you well – what do theyvalue about you?

Would you like to be the person whobrings balance, calm and kindness toeach encounter? By practicing kindnessand compassion to others, you are morelikely to be viewed as a valuable teammember and leader who recognisesother people’s talents rather thansomeone creating dissent and division.Through mindfulness training you canlearn uncomplicated ways to access ease

and balance, especially when the goinggets tough. In other words, emotionalresilience!

5 WAYS TO BE MOREMINDFUL1 Breathe Out

A deceptively simple and easy exercise.Often when we are tense, we breatheshallowly, from the top of our lungs. Bybreathing out, slowly and fully, wenaturally deepen our breath whichstimulates our parasympathetic nervoussystem. A quick and natural way toconsciously relax our bodies and minds.Breathing out before you talk can giveyou that pause you may need to bringyour attention back to the here andnow.

2 Use The 2 Questions to Check-In

What emotions am I experiencing rightnow?

How am I embodying those emotions?

By doing a quick check-in andconsciously noticing what we arefeeling, it helps us realign and rebalanceourselves.

3. Do A Mindfulness Course

You can’t practice mindfulness by

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reading a book! Don’t fall into the trapof buying books on the topic to learnmore - that’s like learning brain surgeryfrom a book. You need a skilledteacher/mentor to support and guideyou plus regular practice.

4. Try Out A Meditation Taster.

If you’d like to try out meditation, whynot listening to a guided meditation? Myhighly experienced meditation teacherSue Weston has a download sound fileavailable for your own use 3.

5. Reframe Your Experience And

Choose Your Attitude

Reframe your narrative of how you areexperiencing life. Not so much being“swept off your feet” by events, more acase of “joyful dancing on a movingcarpet”.

You can choose to change yourattitude to life. Do you find yourselfseeing the worst, being negative,judging others or jumping to rapidconclusions? Instead you can choose topractice gratitude more often, be kindto others (without being a doormat)and be impartial. By cultivating thesequalities, we become people thatothers want to be around, to show trueleadership and live more authentic,healthy, happier lives.

Why wouldn’t you want more of that?

MORE ABOUT THE AUTHORSSharon Leighton.

Sharon runs a successful MedicalInformation consultancy; training andmentoring business helping busymanagers in Medical Informationachieve their goals. She is well knownfor presenting at conferences onglobalization, quality management,organizational change and customerexperience. She also teaches leadershipand mentors new managers.

Website: www.sharonleighton.co.ukBlog: www.sharonleighton.co.uk/newsFind her on Facebook, Pinterest, Twitterand LinkedIn

Sue Weston

Sue has been practicing and teachingmindfulness, T’ai-Chi and Qigong formany years and has PG Diploma inMindfulness Studies from AberdeenUniversity and Samyé College. Sue is theinitiator of Relaxing The Mind activitiesproviding T’ai-Chi, Qigong andmindfulness courses locally inMonmouth and surroundings, includingresidential retreats over 2 weekends. Shealso runs a week retreat each summeron Holy Isle, Scotland. Website:www.sueweston.com

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| REFERENCES1. Chaskalson, M. The Mindful Workplace: developing resilient individuals and resonant

organizations with MSBR. Wiley-Blackwell. 2011

2. How I go into mindfulness. (February 26th 2013). Blog post written by Sharon Leighton.Retrieved from www.sharonleighton.co.uk website.http://www.sharonleighton.co.uk/how-i-got-into-mindfulness/. Accessed 22nd February2018

3. Coming Home to the Breath – guided meditation sound file for download. Retrieved fromhttps://insighttimer.com/relaxingthemind/guided-meditations/coming-home-to-the-breath Accessed 22nd February 2018

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Liz Clark

REVIEWS

23

Charisma Masterclass Review

“DO YOU LOOK in your wardrobe anddecide you want to look second besttoday?” This comment from an imageconsultant was stirred when I recentlyattended a ‘Charisma Masterclass’ andrealised that I could be bringing moreof myself to my work interactions. Butas with many aspects of behaviour,whilst we might know what we areaiming for, the question is how to goabout achieving it.

Google charisma and you will getnearly 14 million hits; add the word‘Research’ and you will see that they arenot just from the realms of thepopularist self-improvement genre, butthat there is a burgeoning wealth ofserious research in the appliedpsychology arena. This confirms the factthat sensed charisma not only predictsreal-world outcomes1, but can betaught2.

A few hits down my Google search, aBBC news article, “Can you be taught tobe more charismatic” featuring aLondon based masterclass caught myeye. The rest is history, as they say andit was not long before I had signed upmyself to learn more.

Enter Richard Reid, and James Kirk,from the Pinnacle Therapy Businessteam, a psychologist, and actorrespectively, who specialise inworkplace psychology andcommunication.

It turns out that this sensed, yetungraspable quality is embodied viathree main qualities: Presence, Powerand Warmth. It is when these areoptimally titrated that the ‘magic’

happens. However, it is one thinggaining insight into what is needed,another knowing how to do it, and afurther challenge developing thepractical skills to actually deliver it. Andwe were about to explore, practice anddevelop each of these interwovenstrands.

Having been lulled into a sense of easeby a reflective and somewhatphilosophical start, reality hit with thefirst practical exercise. Much as I wouldlove to share the detail of the ensuingchallenge, it would be a spoiler forfuture attendees. Suffice to say it threwdown a baseline and got us focused onthe specific things we needed to do tohit that charisma sweetspot.

Being charismatic requires authenticityand personal stability through whichenergy can be channelled. Richard andJames led us gently but firmly throughsome basic exercises – the scales andarpeggios of charismaticcommunication. We explored centringand grounding in that crucial ‘momentbefore’, consciously managing bodylanguage, and using short sentences forgreater impact. Practical, yet remarkablypowerful exercises enabled us todevelop new skills whilst also providingtools for further consolidation anddevelopment. As with all newtechniques they felt awkward andclunky at first, but as we got stuck inwe started to realise that we werestarting to get the hang of things andour confidence rose – perhaps to anextent we underestimated.

Underpinning these practical skills wasa surprising amount of theory: Theneurobiology and interplay of emotions

REVIEWS

PHARMACEUTICAL PHYSICIAN

and cognition; mindfulness; unhelpfulthought patterns; fixed and growthmindsets; conflict models and the roleof purpose. In addition to a set ofcomprehensive course notes, we cameaway with a recommended furtherreading list and pointers to furthermaterial that arose from discussion. Thelatter reflected one of the most valuablefeatures of Richard and James’ approach- the depth of knowledge andwillingness to flex and adapt to theindividual needs and interests of theattendees. But what you don’t get frombooks is the chance to try the practicalelements and get bespoke input fromexperts. It is this practice of appliedtheory combined with a manageablebalance of highly focused feedback thatmakes this course so effective.

When we re-ran the exercise on thesecond day, we all performed betterthan we had on day one. No greatsurprises there perhaps, given theamount of coaching we had received.

Less anticipated and pleasantlyrewarding was the extent of the impact.This continued to build over thefollowing days and weeks, igniting avirtuous circle. Colleagues commentedspontaneously on warmer, moreengaging communication. One evenwent so far as to label a presentation“inspirational”! This appeared to be acommon experience for all of us whohave continued to correspond,comments including: “The more timepasses, the more I realise how much Ienjoyed the course”; “Richard’s coursemade me raise my eyebrows aboutmyself”; “Last weekend switched thelights on again”.

Further information on the CharismaMasterclass can be found on:https://pinnacletherapy.co.uk/open-courses/charisma-masterclass/

By Dr Liz Clark

Vice President Medical Affairs,

Norgine

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| REFERENCES1. Tskhay, K. O., Zhu, R., Zou, C., & Rule, N. O. (2018). Charisma in everyday life:

Conceptualization and validation of the General Charisma Inventory. Journal ofPersonality and Social Psychology, 114(1), 131-152.

2. Antonakis, J., Fenley, M., & Liechti, S. (2011). Can Charisma Be Taught? Tests of TwoInterventions. Academy of Management Learning & Education, 10(3), 374-396.

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Joseph Chiesa

TRIBUTE: to Joseph Chiesa

1944 -2017

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IT IS WITH great sadness that I have toreport that Joseph Chiesa died suddenlyon 12 September 2017. He was apartner in TranScrip for a relativelyshort period but he was well known toand very much respected by most of usfor many years, during which time hecontributed hugely to pharmaceuticalmedicine.

He had a distinguished career workingfor both large and small pharmaceuticalcompanies and CROs. He supported thedesign of early research for a wholerange of our modern medicines. Hewas one of the first Fellows of theFaculty of Pharmaceutical Medicine anda Member of the Education Committeeand Board of Examiners and a visitingprofessor at the University of Salvador(Argentina). Joseph originally graduated from theSchool of Medicine at the University ofBuenos Aires in 1969, receiving hisMedical diploma in 1970. He receivedhis diploma of Clinical Pharmacology in1976 and in 1981 he achieved hisDiploma of Specialist in InternalMedicine and was awarded best thesisfrom the Post Graduate School of theAMA for his work on “Physiological andtherapeutic roles of prostaglandins”.As well as having an awesomecurriculum vitae, he was a wonderfulperson, always cheerful in the officeand a real pleasure to work with. Healways had time for everyone and hewill be sorely missed for this and for hisdeeply knowledgeable and creativethinking.

Our thoughts are with Joseph’s wife andfamily.

Flic Gabbay

Dr Joseph Chiesa – A personal

reflection

I FIRST MET Joseph when I was askedto join the international division of ICIin the early 1990’s. At that stage wewere housed in Portakabins at the northend of the mere in Alderley Park. Theywere a bit rickety and leaked duringheavy rain, our primitive PCs frequentlyfalling victim to rain through the room.There were also “walkways” betweenthe cabins and Joseph was quite anexpert at the game of who can pushwho off and almost into the lake. Hewas quite nippy and a master of theblind side attack. Joseph coveredHispanic countries and I had the MiddleEast. Both of us were bringing “new”medicines including propofol to thesemarkets. I had an insight here as an ex-anaesthetist, and Joseph’s expertise ininternal medicine and pharmacologyhelped with several other drugs.Anecdotes and advice were swapped onthe walkways over sandwich lunches inthe summer or in the on-site pub (yes, areal pub) when it was colder. On oneof the summer days I nearly did Josepha mischief while relating a tale ofmisfortune from Egypt. The countrymanager had decided that I should visitthe pyramids while en-route to see theminister of health. I was suited andbooted, not really the best attire forbeing squashed into a narrow stonepassage way. I finally got wedged andcouldn’t move further forward so had toretreat against the flow of humanity inthe opposite direction. Filthy and with atorn shirt I emerged, while the countrymanager tut-tutted about me being in apoor state to meet the minister, while Itried to remind him that it was his ideato get me in there in the first place. Theanecdote so amused Joseph that he

TRIBUTE:

To Joseph Chiesa

PHARMACEUTICAL PHYSICIAN

started choking on his sandwich,requiring a quick Heimlich manoeuvrefrom our team leader! We used our timeat Alderley Park to help the wholeInternational group to broaden itsinfluence in a great many countries.Occasionally we’d adjourn to theaforementioned pub at the close of theweek and though he struggled manfully,Joseph never really got to like ourwarm flat local brew, much preferring acold cerveza.

When I moved on to pastures new, ourpaths would cross at irregular intervalsat BrAPP meetings, at Faculty andDIA/EMA meetings while endeavouringto keep ourselves up to date. Josephwas an enthusiast about the educationof pharmaceutical physicians and wewere both involved with the Facultyeducation committee at various times.We also were appointed to the board ofexaminers and both tried hard toremove the image of the board beingheartless automatons trying to failcandidates. We both worked onworking parties that undertook revisionsof the PMST syllabus, though we don’taccept blame for the sections that weweren’t involved with! We workedtogether on BrAPP meetings and Josephwas a regular attender of theAssociation’s education days.

When Joseph joined Covance in Leedshe sought me out to help with some ofthe educational activities at the site andI also became the specialty advisor forthe site. We had lengthy discussionsabout the what/how/when ofeducational activities, much time wasspent ensuring that maximum learningopportunities were made available. Thetrainees at the site benefitted fromhaving a committed medical directorwho was very keen for them to developand to document their learning andwho was willing to grant time to ensureit was completed.

Joseph knew a lot of folk within thisincestuous industry so when Imentioned one day that a client of minewas having a problem with cold chain

delivery, he said that he’d ask around. Afew days later I was provided with acontact at a company that producedrefrigerated portable containers withsolar panels to provide power. My clientbought a considerable number and theirproblem was solved, however neitherJoseph nor I was ever credited withfinding the solution.

We continued to work together when Iacted as an independent medicalmonitor for some of the phase 1 studiesin Leeds. Small (often biotech) clientslacked the requisite expertise toevaluate subject safety, thus I was askedto fulfil the role on their behalf. Mostlythis relationship ran smoothly, butoccasionally clients wanted to progressa bit further than Joseph or I deemedappropriate and some terse words werehad with the clients. Joseph alwaysprevailed, as his passion was to ensurethe very highest standards of subjectsafety was maintained. A couple oftimes I was interviewed by MHRA aspart of GCP audits of the Covance siteand I am pleased to say that these wentwell, and no critical findings wereobserved.

Joseph was involved with IFAPP andtreasured the hope that he might oneday set up a formal training course forpharmaceutical physicians in Argentinaand that this might be a model formuch of Latin America. Sadly, the stateuniversity was not enthused, but at leastone private university did want toexplore this project. Despite Joseph’senthusiasm progress was painfully slowand he never realised his ambition.

Joseph’s untimely death robbed hisfamily of a fine dad and grandad,clinical pharmacology of a keeninvestigative mind, pharmaceuticalmedicine of a true professional andmany people of a good and loyalfriend. He is and will continue to begreatly missed.

Dr David BlowersBrAPP Honorary Chairman

April 2018

volume 28 | spring

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April 2018

volume 28 | springPHARMACEUTICAL PHYSICIAN

Peter Jay

TRIBUTE: to Peter Jay MIPI. MFPM

1939-2018

by Jane Barrett

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WE HAVE RECEIVED the sad news thatPeter Jay died in February at the age of79 after a long illness. He was known tomany BrAPP members for his activitiesin MedicoLegal Investigations, aspecialised organisation to investigateclinical trial fraud and misconduct thathe set up with our own Dr Frank Wellsin 1996. He was pivotal in thesuccessful prosecution of a number ofdoctors found to be committingresearch fraud, several of them overmany years. Peter was involved intraining many of us in how to preventand spot fraud, and he was always awise and sympathetic ear to anyoneconcerned about the validity of theirresearch results. His advice was clear,sound, and always relevant.

Peter’s first career was with theMetropolitan Police, reaching the rankof Detective Chief Inspector, and hewas the officer who arrested DennisNilsen, Britain’s most prolific serial killeruntil Harold Shipman. Nilsen, alsoknown as the Muswell Hill Killer, killed15 young men in the late 1970s andearly 1980s, and dismembered theirbodies. Peter arrested him after beingcalled by workmen who had identifiedhuman remains as the cause of a drainblockage. He kept in touch with Nilsenin custody, and Nilsen later said he wasthe only person who had shown himhumanity. Peter was frequentlyinterviewed and filmed in connectionwith the case, and as recently as 2016appeared on television in adocumentary with Trevor McDonald.

On a memorable afternoon a few yearsago, Peter took the then BrAPPcommittee to Scotland Yard to visit theCrime Museum, where certain crime

scenes are reconstructed. He showed usa mock-up of Nilsen’s kitchen, with theactual stove and large saucepan used toboil down his victims’ remains. Hemade the story come alive; truly goose-bump producing.

But it is for his dedication to stampingout research fraud that Peter will bebest remembered in our industry. Thiscommitment was recognised by theFaculty of Pharmaceutical Medicine withHonorary Membership, an award Peteraccepted with joy and humility in equalpart. I was proud to nominate him forthe honour, and to read his citation atthe ceremony.

Peter was a wonderful friend andcolleague, a wise counsel, a greatsupporter of those in need, andincredibly brave throughout his long-drawn out final illness. He will be muchmissed, and our thoughts are with hiswife Linda, sons and grandchildren.