Dr. Fred Baughman is a retired neurologist who has been on my list since day one. I met Dr. Baughman in Pasadena in 2003 when myself and a small group of survivors held  a  (liquids only) hunger strike that lasted 21 days. The "Fast for Freedom" pressed for human rights and choice in psychiatry and demanded that the mental health industry produce even one study proving the common industry claim that 'mental illness is biologically-based.

Baughman says the ADHD "epidemic" is pure fraud and a product of disease mongering by the drug industry and the other vested interests. I agree.

Dr. Baughman wrote a great book on this topic that should be on everyones book shelf. His The ADHD Fraud: How Psychiatry Makes "Patients" of Normal Children is not one for the squeamish or for those who have trouble sleeping at night. Jim Torlakson provided the graphic above.  You may see his work and that of other list member/artists at Emma Holister's Art Margin site.  On March 15, 2004, Jim's daughter Elizabeth was just 21 years when she entered a closed BART tunnel in San Francisco and threw herself in front of a train. She had been under the care of a doctor who had prescribed the drug Celexa to treat her depression. SSRI suicides are always extremely violent. Harvard's Dr. Joseph Glenmullen says these suicides are inevitably accompanied by drug-induced akathesia (extreme agitation) to the extent one would do anything to escape this inner turmoil. A survivor described the thought processes before pulling a trigger as inconsequential as deciding to have her nails done.  Another survivor told me the urge to die was as compulsive as sneezing. The drug companies concealed their studies that showed this effect from the public for more than twenty years.  Their internal memos confirmed they were concerned that if this information that if made public it would hurt sales. The callous disregard for public safety in favor of bonuses and bottom lines cost Jim Torlakson his beloved daughter. Vince http://www.foxbusiness.com/article/northern-illinois-university-murders-chemical-imbalances-chemical-balancers_490227_1.html        Thursday, Feb. 21 2008

'The Northern Illinois University Murders Due to 'Chemical Imbalances' or 'Chemical Balancers' - Drugs?'

Fred A. Baughman Jr., MD, Neurologist/Child Neurologist

This email address is being protected from spambots. You need JavaScript enabled to view it. Comtex

EL CAJON, Calif., Feb 21, 2008 /PRNewswire via COMTEX/ -- Writing of the Northern Illinois University shooter, Steven P. Kazmierczak, The New York Times (Benedict Carey, 2/19/08, A20) remarks " ... doctors say it is almost impossible to tell whether the spasms of violence stem in part from the drug reactions or the underlying illnesses." A girlfriend said Kazmierczac took Prozac to battle anxiety and compulsive behavior. While psychiatry (psychology too) and the pharmaceutical industry want anxiety, depression, elation impulsiveness, poor conduct, trouble with math, reading, writing,   Dr. Fred Baughman   etc., portrayed as brain abnormalities/diseases/disorders/ syndromes, so as to be able to portray their drugs as "treatments," throughout medical recorded history, there is no such thing as an demonstrable physical abnormality/disease in all of psychiatry.

Diseases of the brain, multiple sclerosis, amyotrophic lateral sclerosis-Lou Gehrig's disease, stroke, meningitis, etc., are the province of neurology, my specialty. This was assured in 1948 when the two specialties were formally split with "neuropsychiatry" becoming the separate, new specialties, "psychiatry" and "neurology." This means that the drugs prescribed by psychiatrists (and throughout mental health, by all sorts of doctors) are toxins/poisons, the first and only demonstrable abnormality/disease that psychiatric patients have. But today, patients are lied to -- told, for purposes of informed consent, that they have a disease or chemical imbalance. This gains their consent. Whether it is actual informed consent is irrelevant to the pharmaceutical companies. There is little doubt that without the "chemical imbalance" lie the epidemic psychiatric drug poisoning would be a small fraction of what it is today.

As in the University of Northern Illinois case, almost all of the high school, and college shooters have been psychiatric patients on a diet of psychiatric drugs. Nor is the issue of whether they still have the poison in their system or not critical. All psychiatric drugs damage the previously normal brain and body. This is how they alter the subjective symptoms for which they are said to be "treatment." Even if stopped they have altered and thus damaged the previously normal individual.

At a 1970 Congressional hearing on the drugging of school children where hyperactivity was first called a brain disease, Dr John D. Griffith, Assistant Professor of Psychiatry, Vanderbilt University School of Medicine, testified: "I would like to point out that every drug, however innocuous, has some degree of toxicity. A drug, therefore, is a type of poison and its poisonous qualities must be carefully weighed against its therapeutic usefulness." Such a scientific, weighing of the risks vs. the benefits of psychiatric medications is virtually never carried out today because the psychiatric diagnosis, never a "chemical imbalance"/disease, is always portrayed as one. Why? Because the psychiatric diagnosis is almost always portrayed as one requiring treatment with a "chemical balancer", or pill. Every year, tens of thousands of children are court-ordered to take psychiatric drugs for diagnoses such as ADHD, conduct and oppositional-defiant disorders. Should their parents refuse, then, without trial, the parents are pronounced "medically negligent" and threatened with the loss of custody of the child -- their child. Their child whose emotional life they are no longer allowed to direct. This is what we have come to in the USA!

Eric Harris, who was denied enlistment into the armed services, and one of the two Columbine shooters, had been on Zoloft, a Prozac-like antidepressant. There is no such thing as the balancing of the "chemical imbalance" portrayed in the Zoloft ad. And yet the FDA, as much a part of the pharmaceutical enterprise as psychiatry, allows the pharmaceuticals to peddle their lies directly to the American public via publicly-owned airwaves.

Today, in the US, we have been so taken in by the "chemical imbalance"/ "chemical balancer" lie that 9-10 million school children are on one or more psychiatric drugs, including 60-70% of those in foster care (who cannot defend themselves). At the same time psychiatry asks us to believe that half of all of us in the US will one day be afflicted with a "serious mental disorder"/ "chemical imbalance" ("Are we all going mad, or are the experts crazy?" Stuart A. Kirk, Los Angeles Times, August 14, 2005) and that they too will need one or more "chemical balancers"/drugs.      By 

Fred A. Baughman Jr., MD Neurologist/Child Neurologist

           SOURCE Fred A. Baughman Jr., MD





U.K. study casts doubt on antidepressant drugs Researchers find placebos work just as well in many patients WASHINGTON - Antidepressant medications appear to help only very severely depressed people and work no better than placebos in many patients, British researchers said. Researchers led by Irving Kirsch of the University of Hull reviewed a series of studies, both published and unpublished, on four antidepressants, examining the question of whether a person's response to these drugs hinged on how depressed they were before getting treatment. They were Eli Lilly and Co.'s Prozac, also known as fluoxetine, Wyeth's Effexor, also called venlafaxine; GlaxoSmithKline's Paxil, also called Seroxat or paroxetine, and Bristol-Myers Squibb Co's drug Serzone, also called nefazodone, which it no longer markets in the United States. ,,,   The researchers obtained data on all the clinical trials submitted to the U.S. Food and Drug Administration for the licensing of the four drugs.    "Although patients get better when they take antidepressants, they also get better when they take a placebo, and the difference in improvement is not very great. This means that depressed people can improve without chemical treatments," Kirsch said in a statement.    More here: http://www.msnbc.msn.com/id/23348068/ 




Prozac, used by 40m people, does not work say scientists

A single Prozac capsule.

Prozac, the bestselling antidepressant taken by 40 million people worldwide, does not work and nor do similar drugs in the same class, according to a major review released today.

The study examined all available data on the drugs, including results from clinical trials that the manufacturers chose not to publish at the time. The trials compared the effect on patients taking the drugs with those given a placebo or sugar pill.

 ...  "Given these results, there seems little reason to prescribe antidepressant medication to any but the most severely depressed patients, unless alternative treatments have failed," says Kirsch. "This study raises serious issues that need to be addressed surrounding drug licensing and how drug trial data is reported."

The paper, published today in the journal PLoS (Public Library of Science) Medicine, is likely to have a significant impact on the prescribing of the drugs. The National Institute for Health and Clinical Excellence (Nice) already recommends that counselling should be tried before doctors prescribe antidepressants. Kirsch, who was one of the consultants for the guidelines, says the new analysis "would suggest that the prescription of antidepressant medications might be restricted even more".

The review breaks new ground because Kirsch and his colleagues have obtained for the first time what they believe is a full set of trial data for four antidepressants.

They requested the full data under freedom of information rules from the Food and Drug Administration, which licenses medicines in the US and requires all data when it makes a decision.

More here: http://www.guardian.co.uk/society/2008/feb/26/mentalhealth.medicalresearch

25,180 Signatures Against TeenScreen.     Video:  http://www.youtube.com/watch?v=RfU9puZQKBY  Petition: English   http://www.petitiononline.com/TScreen/petition.html  Spanish http://www.psychsearch.net/votos.html Italian     http://www.psychsearch.net/italiani.html French   http://www.psychsearch.net/francais.html  
                                                                                                   Vera Sharav http://www.ahrp.org and http://ahrp.blogspot.com FYI "Initial Severity and Antidepressant Benefits: A Meta-Analysis of Data Submitted to the Food and Drug Administration" by Irving Kirsch, Brett J. Deacon, Tania B. Huedo-Medina, Alan Scoboria, Thomas J. Moore, Blair T. Johnson, has just been published in PLoS (Public Library of Science) The study addresses the clinical question: is the risk / benefit ratio of antidepressants favorable for patient use? The conclusion: "compared with placebo, the new-generation antidepressants do not produce clinically significant improvements in depression in patients who initially have moderate or even very severe depression." http://medicine.plosjournals.org/archive/1549-1676/5/2/pdf/10.1371_journal.p med.0050045-L.pdf This new study by expands the authors' previous analysis, The Emperor's New Drugs (2006) [1] as well an earlier analysis by the principle author (2005). [2] The just released study utilizes additional--decades old data--released to the authors by the FDA. The authors note: "Meta-analyses of antidepressant medications have reported only modest benefits over placebo treatment, and when unpublished trial data are included, the benefit falls below accepted criteria for clinical significance. Yet, the efficacy of the antidepressants may also depend on the severity of initial depression scores. The purpose of this analysis is to establish the relation of baseline severity and antidepressant efficacy using a relevant dataset of published and unpublished clinical trials." "Conventional meta-analyses are often limited to published data. In the case of antidepressant medication, this limitation has been found to result in considerable reporting bias characterized by multiple publication, selective publication, and selective reporting in studies sponsored by pharmaceutical companies. To avoid publication bias, we evaluated a dataset that includes the complete data from all trials of the medications, whether or not they were published. Specifically, we analyzed the data submitted to the FDA for the licensing of four new-generation antidepressants for which full data, published and unpublished, were available. As part of the licensing process, the FDA requires drug companies to report ''all controlled studies related to each proposed indication'' (emphasis in original). Thus, there should be no reporting bias in the dataset we analyze." We challenge the FDA on two points: 1. If independent analyses of data submitted to the FDA conclude that the drugs failed to demonstrate clinical improvement and the drugs' safety profile shows serious risks of harm--including increased suicides and suicide attempts--one has to question the FDA approval process. What was the safety and efficacy standard used by the FDA to justify approval of the new generation antidepressant and antipsychotic drugs ? The question undercuts current legal arguments deferring all drug safety issues to the FDA: the preemption arguments presuppose a scrupulous, rigorous scientific FDA standard for approval and drug labeling. That presumption is not credible in light of the evidence demonstrating FDA's failure to analyze SSRI safety and efficacy data for more than 15 years. 2. Despite wide acknowledgement that published clinical drug trial reports are biased and unrepresentative of the data, what justification is there for FDA's recent Proposed Guidance for Industry that would legalize the illegal marketing / promotion of drugs for off-label uses? See, DRAFT GUIDANCE http://www.fda.gov/oc/op/goodreprint.html Underscoring the significance of the PLos study findings, the government sponsored STAR*D naturalistic uncontrolled observational study confirmed the lack of antidepressant efficacy. See: Separating the Facts from the Propaganda_Latest Findings of Depression Study http://www.ahrp.org/cms/content/view/374/28/ The conundrum for industry and psychiatry is lack scientific evidence to support the safety and effectiveness of these drugs: First, the exceedingly high placebo effect (80%) demonstrated in controlled clinical trial data submitted to the FDA [1] [2]; and second, severe adverse effects-including a twofold increased risk of suicidal behavior-now acknowledged on the drugs' label. These negative facts have led psychiatrists whose career is invested in the drugs to turn to epidemiological data [5] [6]. References: 1. Irving Kirsch, Thomas J. Moore, Alan Scoboria, and Sarah S. Nicholls The Emperor's New Drugs: An Analysis of Antidepressant Medication Data Submitted to the U.S. Food and Drug Administration, Prevention & Treatment Volume Five July 15, 2002. Target article with 9 commentaries. 2. Joanna Moncrieff and Irving Kirsch Efficacy of Antidepressants in Adults, BMJ, 2005;331:155-157. Contact: Vera Hassner Sharav This email address is being protected from spambots. You need JavaScript enabled to view it. 212-595-8974
Tithe an OireachtaisAn Comchoiste um Shlainte agus LeanaiAn tOchtú TuarascáilSeachthorthaí Dochracha Táirgí CógaisíochtaAibreán 2007_____________Houses of the OireachtasJoint Committee on Health and ChildrenEighth ReportThe Adverse Side Effects of PharmaceuticalsApril 2007(Prn. A7/0561)iiiiiForeword by the chairman of the Joint Committee on Health &Children, John Moloney, T.D.The Joint Committee on Health and Children was established in November 2002. Inresponse to concerns expressed by professionals and members of the public, the JointCommittee agreed to establish a sub-Committee on the Adverse Side Effects ofPharmaceuticals to examine the issue in detail and report back with a series of reasonableand feasible recommendations.The sub-Committee held its inaugural meeting in May 2006 when it decided to invitewritten submissions from the public followed up by oral presentations from selectedwitnesses.The sub-Committee agreed to engage the services of a consultant to assist it in thepreparation of a draft report.The sub-Committee appointed Mr. Jim Dorgan, of Curtin Dorgan Associates to assist itin producing a draft Report containing a series of reasonable and feasiblerecommendations. A draft report was drawn up by Mr. Dorgan and agreed by the sub-Committee and referred to the Joint Committee in April 2007. The draft report wasagreed.The Joint Committee is grateful to the Members of the sub-Committee for their work onsuch an important issue. Members of the sub-Committee were Deputies PaudgevTABLE OF CONTENTSForewordExecutive Summary 1I Background 5Purpose of the Sub-Committee 5Role of Pharmaceuticals in Health Care 6Impact of Medicines on Health 8Economic Significance of the PharmaceuticalsIndustry 9II The Pharmaceutical Industry and Regulation 11Drug Development Process 11Commercial Aspects of Drug Development 11Regulatory Environment: The Irish Medicines Board 13Powers of the IMB 14European Medicines Evaluation Agency 14III Adverse Drug Reactions 17Definition 17Causes of ADRs 17Consequences of ADRs 18Reporting ADRs 20Under Reporting 22Processing ADR Reports 24Communication with Prescribers 24IV Submissions to the Sub-Committee 27Psychiatric Medicines 27Drug Trials 28Regulatory ‘Capture’ 28viReporting ADRs 29Medical Error 29‘Medicalisation’ 30Promotion by Drug Companies 30Reporting of ADRs by Patients 32V Conclusions and Recommendations 33Conclusions 33Recommendations 34Regulation 34FundingTrialsPharmacovigilanceReporting of Adverse Drug ReactionsDisease Awareness Advertising by thePharmaceutical CompaniesProfession 36TrainingConflicts of InterestFormulariesHealth Services 38Information SystemsPharmacyPscyhological Support ServicesThe Public 40Patient Safety Agency 41Appendix 1: Orders of Reference 45Appendix 2: List of Oral Submissions 49Appendix 3: Membership of Joint Committee 53Membership of sub-Committee on theAdverse Side Effects of Pharmaceuticals 55viiAbbreviationsADR Adverse drug reactionDTCA Direct to Consumer AdvertisingEMEA European Medical Evaluation AgencyFTIM First Time in Man (Phase I clinical trials)GMS General Medical ServicesHOC House of CommonsHPU Health Promotion UnitHSE Health Service ExecutiveIMB Irish Medicines BoardIPHA Irish Pharmaceuticals Healthcare AssociationMIMS Monthly Index of Medical SpecialitiesMAH Market Authorisation HoldersNDAB National Drugs Advisory BoardNPM Non prescription medicine for sale in a pharmacy onlyNHS National Health Service (UK)OTC Over the counter (non prescription) medicineOECD Organisation for Economic Cooperation and DevelopmentPIL Patient Information LeafletPOM Prescription only medicinePCRS Primary Care Reimbursement ServiceSPC Summary of Product CharacteristicsWHO World Health Organisationviii1EXECUTIVE SUMMARY1. In recent years, concern has been expressed that the role of pharmaceuticals in thehealth services is excessive and that some in particular have dangerous sideeffects which have been overlooked or ignored.2. In response to this, the Joint Committee on Health and Children set up the Sub-Committee on Adverse Side Effects of Pharmaceuticals. The Sub-Committeereceived written and oral evidence from a number of organisations andindividuals.3. The purpose of this report is to review the use of pharmaceuticals and theiradverse effects (referred to as Adverse Drug Reactions or ADRs) in the light ofthese submissions, and to make recommendations. Because of limited time andresources, the Sub-Committee’s report can be regarded only as preliminary work.4. Submissions to the Sub-Committee included a number which made specificcriticisms of the use of about psychiatric pharmaceuticals. It was asserted thatthese medicines had dangerous, even fatal side effects, yet were prescribedextensively.5. Other concerns expressed included:i. The danger that regulatory authorities are unduly influenced bydrug companies because of the latter’s economic and technicalresources;ii. Shortcomings in the conduct of drug trials;iii. Insufficient ADR reporting leading to failure to identify and copewith problematic side effects of pharmaceuticals;iv. The need for improved training in pharmacology for doctors,including continuous in service training;v. The ‘medicalisation’ or ‘pill for every ill’ culture, partly the resultof promotion by drug companies, leading to excessive use ofpharmaceuticals with attendant ADRs.vi. Some types of promotional activity by drug companies targeted atdoctors.2vii. Misuse of drugs by the public through self medication, importationof non-prescribed drugs from abroad and failure to followprescribers’ instructions.6. The Sub-Committee has concluded that in general, while pharmaceuticals haveundoubtedly brought benefits, there is excessive reliance on them to the neglect ofother forms of therapy and this contributes to high rates of adverse reactions.7. Subject to a major review being undertaken, the Sub-Committee believes thefollowing proposals should be consideredi) Fees for the services of the IMB should be paid by drug companies to theDepartment of Health and Children which should pass them to the IMB in the form ofan annual grant.ii) Drug trials should approximate to conditions in routine clinical settings andshould include comparisons with well established medicines and non-drugapproachesiii) The licensing process should begin before human trials (Stage I Trials) take placeiv) The pharmacovigilance section of the IMB, dealing with post-marketingmonitoring of pharmaceuticals, should be set up as an independent entity so as toreduce the possibility of a conflict of interest with the licensing activity of the IMB.v) There is a need for large scale studies after drugs have entered circulation (PhaseIV). Since drug companies invest relatively little in such studies funds should beavailable to the IMB to commission such studies - perhaps in collaboration with otheragencies and research bodies.vi) The reporting of ADRs, which occur, needs to be increased. Thepharmacovigilance activity of the IMB should expand its training and promotion ofADR reporting. Patient reporting of ADRs should be encouraged. It should bepossible to reports ADRs on-line. .vii) There should be a coordinated approach by the Department and the Health3Promotions Unit to ensure that disease awareness material does not indirectlypromote drug therapies, and to ensure that national health priorities are addressed.viii)There is a need to expand the amount of pharmacology training for doctors withinthe context of Continuing Medical Education in order to ensure that they are fullyinformed of latest developments in this fast changing field..ix) The Medical Council should review its rules on ethics of conflict of interestcreated by certain types of promotional activity by drug companies directed atmedical practitioners.x) Action needs to be taken to provide an independent and practical source ofinformation on pharmaceuticals at national and or local level as exists in othercountries such as the UK.xi) An integrated patient record system should be created to ensure that prescribershave ready access to all relevant information on patientsxii) Records of the Primary Care Reimbursement Service should be exploited toprovide information on trends in drug consumption.xiii) Software to support drug decision making in Irish conditions should bedeveloped and distributed to hospitals, doctors and pharmacists together withfacilities to permit printing of prescriptions as a rule so as to avoid errors due toshortcomings in spelling or legibility .xiv) The role for the pharmacist in community health should be expanded andprovision made for regular medication reviews for all patientsxv) There should be an expansion of counselling and psychotherapy in theCommunity Health Services in order to provide alternatives to psychiatric drugtherapies.xvi) There is a need for public information campaigns to improve public attitudes tothe proper use of drugs including:4a. Advising patients that many medical problems are self limiting and they shouldnot always demand or expect prescriptions when they visit doctors;b. Encouraging compliance with courses when a prescription is given;c. Disposing safely of unused pharmaceuticals in collaboration with pharmacists;d. Raising awareness of the dangers of self-prescribed medicines includingcounterfeit and imported drugs;e. Promoting awareness of ADRs among patients and of the desirability and themeans of reporting them to the IMBA Patient Safety Agency would be the appropriate body to implement many of theserecommendations. The Sub-Committee recommends that such an agency beestablished.5I BACKGROUNDPurpose of the Sub-Committee1.1 In recent years concern has been expressed about the role of pharmaceuticals inmodern medicine. Critics have pointed to the rapid increase in consumption of medicinesand have concluded that this is at the expense of alternative, more effective forms oftherapy. There have also been criticisms of specific drugs which have had adverse effectsand which, it is contended, should never have been licensed for general use. Many ofthese problems have been attributed to the power and influence of the drug industrywhich, it is argued, has led regulators and professionals to take an unduly positive viewof the claims of the pharmaceutical companies about their products.1.2 It is against this background that the Joint Committee on Health and Childrendecided to investigate the problem of the adverse effects of pharmaceuticals. It assignedthe task to a Sub-Committee under the chairmanship of Deputy Paudge Connolly whichcommenced work on 9 May 2006. At that time, the Sub-Committee decided to advertisein the press for submissions from the public. Subsequently items were received from 17individuals or organisations. Between 10 October 2006 and 7 November 2006 the Sub-Committee held public hearings at which a total of eleven individuals and organisationsmade oral submissions and in most cases submitted some further written material.1.3 On 28 November 2006 the members of the Sub-Committee met members of theHealth Committee of the House of Commons to discuss aspects of the report which thatCommittee had published in March 2005 on ‘The Influence of the PharmaceuticalIndustry”.1 This report examined a number of issues relevant to the mission of the Sub-Committee.1.4 The concerns which gave rise to the formation of the Sub-Committee havecomplex roots. Pharmacology is an advanced science and its role in medicine isinfluenced by a variety of managerial, political and cultural factors as well as science.However the resources available to the Sub-Committee are limited. In compiling this1 House of Commons Health Committee. Influence of the Pharmaceutical Industry. Fourth Report ofSession 2004-5. HC 42-1, 2005 (‘HOC’).6report the Sub-Committee confined its attention to the written and oral submissionswhich it received and to some additional written material specifically brought to itsattention, especially the report of the Health Committee of the House of Commons. TheSub-Committee recognises that this is not enough to do justice to the subject.Consequently, this report should be seen as a preliminary exploration of the problem ofadverse drug reactions, their causes and consequences and proposals for reducing them.Role of Pharmaceuticals in Health Care1.5 The amount of pharmaceuticals consumed in Ireland is not known exactly. Publicexpenditure on pharmaceuticals is funded from a number of sources including thePrimary Care Reimbursement Service (PCRS, formerly the General Medical ServicesPayments Board), the hospitals and the Health Service Executive. Detailed informationon expenditure, numbers and types of drugs is available from the PCRS but similarinformation from the hospitals and the HSE is not collated centrally. Direct data availableon privately financed consumption of drugs is not available either.1.6 However, from the available data it is clear that drugs play a large and rapidlyrising role in medical treatment. In Ireland, expenditure on health services, both publicand private, have risen from €3.8 billion in 1996 to about €14 billion in 2006.2 Withinthat total expenditures on drugs of all types - prescription only medicines (POMs) andover the counter (OTC) medicines available without prescription - have risen from €400million to €1.7 billion billion, an increase of 325%.3 It should be noted that this includesestimates of private as well as publicly financed purchases. This exceeds the growth ofexpenditure on health generally and means that drugs have risen from 10.5% to about12.5% of health total spending in Ireland. Nevertheless, as Table 1 shows, Irishconsumption of drugs is well below the EU average. (By comparison, per capita healthexpenditure in Ireland is around the EU average and, like drugs, has increased rapidly inrecent years.)2 Based on OECD figures for public and private expenditure up to 2004 and assuming private expenditurehas risen as fast as public expenditure in 2005-06.3 Derived from the application of OECD estimate of ratio of public and private expenditure on drugs tototal health expenditure in 2004 (12.4%) to estimates of total health expenditure in 2005-06.7Table 1 Per Capita Expenditure on Health: US and EU-15 CountriesPer Capita Expenditure on HealthPer Capita Expenditure onPharmaceuticals$Increase1994-04 $Increase1994-04United States 6102 73.6 United States 752 150.7France 3159 64.5 France 599 79.3Austria 3124 81.8 Italy 520 66.7Germany 3043 46.1 Spain 477 107.3Netherlands 3041 74.8 Germany 429 58.3Denmark 2881 57.4 Portugal 421 81.5Sweden 2825 70.8 Austria 407 104.1Ireland 2596 131.2 Greece 377 93.3United Kingdom 2508 88.3 Finland 364 94.7Italy 2467 60.5 Sweden 348 78.5Finland 2235 59.6 Ireland 321 169.7Greece 2162 78.1 Denmark 270 67.8Spain 2094 88.0Portugal 1824 97.4Source: OECD Health Data 2005.$ are in Purchasing Power Parities (PPPs). PPPs allow an accurate comparisons across countries1.7 Table 2 shows some further information on drug consumption drawn from therecords of the PCRS. Public expenditure on drugs has increased by 126% since 2000.Table 2: Public Expenditure on Pharmaceuticals€ millionGMS DP LTI Total2005 831.4 246.7 100.55 1178.72004 763.3 224.0 85.6 1072.92003 650.7 204.4 73.3 928.42002 550.9 192.4 61.6 804.92001 434.0 177.8 52.1 663.92000 338.8 140.6 41.7 521.1Source:8GMS: General Medical Service (‘medical card’) schemeDP: Direct Payments (grant for drugs exceeding aspecified monthly threshold)LTI: Long Term IllnessImpact of Medicines on Health Standards1.8 It is acknowledged by health care professionals and administrators that thedevelopment of new drugs has made a big contribution to the welfare of patients in thelast 50 years. This is manifest in, for example, increased life expectancy, improvedquality of life, reduction of pain and more effective anaesthetics to improve outcomes ofsurgery. A study in the UK referred to by the Irish Pharmaceutical HealthcareAssociation (IPHA) in its submission to the Sub-Committee, has estimated that improvedtreatments in 12 areas of serious illness since the 1950s have reduced hospital bed days inthe UK’s NHS by the equivalent of £11 billion or £4 billion more than the cost ofmedicines. 4Excerpt from Website of Irish Pharmaceutical Healthcare Association“In the past 40 years the use of medicines has helped diminish the number of hospitaladmissions for 12 major diseases by half, including ulcers, mental illness and infectiousdiseases.New treatments for Parkinsons, Alzheimers and diabetes have helped thousands ofpatients to lead better and more normal lives, easing the burden on care givers anddelaying or avoiding costly long-term nursing care. While cholesterol-loweringmedicines, at a cost of less than €3 per day can help avoid coronary by-pass surgery ataround a cost of €75,000.In the space of a lifetime, vaccines have virtually wiped out diseases such as diphtheria,whooping cough, measles and polio.4 HOC, page 13.9By any of these measures, prescription medicines provide some of the best valuehealthcare. Medicines save lives, relieve pain, cure and prevent disease. Medicines helpkeep families together longer and improve the quality of life for patients and caregivers.”1.9 In the Irish environment, a concrete example of benefits in one important area ofhealth care is given by a recently completed study of the decline in deaths attributed tocoronary heart disease. This study, completed in March of 2006 by a team in theDepartment of Pharmacology and Therapeutics, Trinity Centre for Health Sciences, StJames Hospital concluded that 35% of the decline in deaths due to coronary heartdiseases in Ireland in the period 1985-2000 was attributable to medicines (aspirin, betablockers, ACE inhibitors, statins, and similar drugs). Another 8.5% was attributable toother forms of treatment. Most of the remainder is attributable to reduction in risk factorslike smoking, cholesterol and blood pressure levels. 5Economic Significance of Pharmaceutical Industry1.10 The pharmaceutical industry is one of the most important sectors of the Irisheconomy. According to the IPHA it employs a total of 24,000 persons in Ireland anincrease of over 100% in the last ten years. This includes employment in manufacturing,distribution and dispensing. The CSO’s Census of Industrial Production tracks the sizeand development of the manufacturing sector – a smaller but higher value added segment.The data are summarised below and confirm the general picture of the industry from theIPHA. Employment in manufacturing has doubled while the value of output hasincreased nearly seven fold. Almost all of the output of the sector is exported.Table 3:Measures of Economic Significance ofIrish Pharmaceuticals IndustryTurnover Exports Employment2004 5441 5294 88835 Bennett, Kathleen et al. Explaining the Recent Decrease in Coronary Heat Disease Mortality Rates inIreland, 1985-2000. J. Epidemiol. Community Health, 2006. 60:322-327.102003 4474 4336 83242002 5242 5090 88962001 4193 4090 81342000 3130 3024 75091999 3119 71721998 1850 62821997 1457 60121996 1143 53161995 859 4368Source: CSO, Census of Industrial Production11II THE PHARMACEUTICAL INDUSTRY AND REGULATIONDrug Development Process2.1 The development of new drugs tkes a long time and us an expensive and riskyprocess. According to submissions to the House of Commons Health Committee, atypical drug takes 12 years to bring to market. Costs are also high.6 According to theAssociation of the British Pharmaceutical Industry, the average cost of bringing a newdrug to the market is about £750 million. For this reason, while research and testing maybe contracted out, much drug development takes place in large companies.Notwithstanding their size, the success or failure of a single drug can make a substantialdifference to the financial fortunes of the largest companies.72.2 Novelty in the drug enables the companies to enjoy ten years’ patent protectionfrom the time of licensing during which, assuming the drug is effective and has no closesubstitutes, the company has the chance to earn substantial profits. After the period ofprotection, generic copies of the drug can be produced by competitors and the price of thepropriety drug will fall, sometimes precipitously.Commercial Aspects of Drug Developments2.3 Though the large drug companies are generally profitable, there is some evidencethat market conditions are becoming more difficult.8 It is contended that competitionfrom generics is increasing and that health funders - governments and insurancecompanies - are exercising increasing downward pressure on prices. One consequencehas been a certain amount of restructuring in the industry. Other developments, whichmay be attributed to commercial pressures, is that the number of genuinely new drugs isdeclining and that many new drugs in reality are not very different to preparations alreadyon the market (i.e. ‘me too’ drugs). 9 It may also lead companies to lay greater emphasison marketing and promotion and to put pressure on regulatory authorities to accelerte the6 HOC, page 177 The shares of Pfizer, the largest drug company in the world, have been in retreat since the failure of itsanti cholesterol drug Torcetrapib in development, at the end of 2006.8 Pharmaceuticals: Billion Dollar Pills, Economist, January 27, 2007.9 HOC, page 46.12time and reduce the cost of the trial phase.2.4 Table 4 gives details of the stages in the development of a drug.Table 4: Stages in Drug DevelopmentStage Activity Failure Success DurationSelection of a promisingcompound for developmentPre-clinical and non-clinical:testing in laboratory and onanimalsTests on human cells,animal tissues andwhole animals.Of 100 enteringPhase I3years..Phase I: First Time in Man:Tests on humans, usuallyhealthy volunteersTests on 200-300healthy volunteers.30% 70%Phase II: Proof of Concept:Tests in patientsTests in hospital withcooperation of hospitaldoctors. Involves 200-500 patients with thecondition.37% 33%Phase III: Large scale studiesto generate data for licenseapplicationSample expanded to2,000-3,000 andcomparisons made withexisting drugs orplacebos.8% 25%10yearsLicense application 5% 20%Phase IV: Post-marketingstudiesTrials conducted bycompanies or byindependentresearchers to trackefficacy in large scalestudies and over longertermHOC, p1813Regulatory Environment: The Irish Medicines Board2.5 In Ireland the National Drugs Advisory Board (NDAB) advised the Departmentof Health about drug safety matters until 1996 when it was replaced by the IrishMedicines Board (IMB) under the Irish Medicines Board Act, 1995. The members of theIMB, as also the members of Board’s advisory committee on human drugs, are appointedby the Minister for Health. The IMB’s department dealing with human medicines isdivided into licensing and pharmacovigilance sections. The IMB has a budget of €22million of which about 80% is derived from fees from industry (2006).2.6 The task of the IMB is ‘…to ensure so far as possible, consistent with currentmedical and scientific knowledge, the quality, safety and efficacy of medicines availablein Ireland and to participate in systems designed to do that throughout the EuropeanUnion.’10 Quality means that the drug conforms to specifications as to content,uniformity and stability. Safety means that the risks, which are always present in druguse, are acceptable having regard to the expected benefits. Effectiveness means that thedrug is likely to be beneficial in treating the condition for which it has been developed.Table 5: Selected Indicators of Drug Licensing Activities of the IMBNew Applications VariationApplicationsRenewalApplicationsClinical Trials2005 942 15,267 1,328 1192004 749 13,885 1,325 1622003 683 5,407 670 1162002 682 5,365 605 106Source: IMB Annual Report, 2005.10 Gilvarry, Dr Joan, Minutes of Sub-Committee on Adverse Drug Reactions. (‘Minutes’). 31 October2006. .14Powers of the IMB2.7 The statutory powers of the IMB, and equivalent organisations in other developedcountries covers the authorisation of Phase I to Phase III trials involving humans, as wellas authorisation of the finished drug after Phase III (see Table 4). The IMB continues itssurveillance of the drug in the post marketing phase, i.e. after it has been licensed, byexamining the results of the Phase IV trials, by following the literature and by evaluatingspontaneous, that is to say, voluntary reports of adverse reactions as these are reported byhealth care professionals, the companies themselves or patients (the pharmacovigilanceactivity). It should be noted that companies must report all information which may affectthe licensing conditions of their drugs from whatever source.11 The IMB is alsoresponsible for ensuring quality of products in the market and of production facilities.2.8 The powers of the IMB in relation to drugs include, most obviously, refusal toallow tests or to license a product or to order the withdrawal of a drug from the market. Inthe case of drugs which are licensed, the IMB has control over the statement of ‘SpecificProduct Characteristics’ (SPC) and the ‘Patient Information Letter’ (PIL) which drugcompanies must issue. The former is a statement of how the drug may and may not beused (i.e. dosages, duration, contra indications) and is primarily intended forprofessionals. The PIL is information for consumers. The IMB may require changes tothe SPC and PIL as knowledge of the effects of the drug develops with usage.EMEA2.9 The IMB exercises its powers within the context of EU legislation and incollaboration with the European Medicines Agency (EMEA) which was set up the EU in1995, as a ‘community agency’ under the aegis of the Directorate General for Enterprise.Pharmaceutical companies have three approaches to licensing a pharmaceutical:National Procedure by which the company seeks licensing from the nationalagency for the marketing of a drug only in that country.11 Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on theCommunity Code Relating to Medicinal Products for Human Use. Article 23 and Annex 1.15Mutual Recognition where the company obtains a license in one country andsubmits this with its application for licensing in other countries. This is done withinthe framework of the EMEA where any differences of opinion between the memberagencies about the appropriateness of the original license are resolvedCentralised Procedure which means applications are made to the EMEA and areprocessed with the aid of personnel from national agencies and other experts. Whenadopted by the EMEA’s Committee on Human Medicines and the Commission,marketing authorisation is applicable throughout the EU. The centralised proceduremust be used for the licensing of certain drugs (drugs produced throughbiotechnology products and drugs for AIDS, cancer, neurodegenerative disease anddiabetes).2.10 The EMEA is linked with the US and Japanese agencies through the‘International Conference on Harmonisation on Technical Requirements for Registrationof Pharmaceuticals’ (ICH). The ICH has established standards to be observed by allmembers in relation to clinical trials.2..11 The EMEA is currently implementing new legislation which will widen itsresponsibilities “...in particular to speed access by patients to new medicines…”12 Thelist of drug types which must be subject to the centralised procedure is continuallyexpanding.12 Website of the EMEA1617III ADVERSE DRUG REACTIONSDefinition3.1 ADRs is defined by the governing EU Directive as:A response to a medicinal product which is noxious and unintended and which occurs atdoses normally used in man for prophylaxis, diagnoses or therapy of disease or for therestoration, correction or modification of physiological function. 133.2 In practice, concern about adverse effects of drugs extends more widely thanwhen they arise in ‘doses normally used in man..’ 14. As reflected in the submissions tothe Sub-Committee, there are concerns about the reactions to excessive use of drugs inmedical treatment , and to improper use of drugs as a result of failure by professionals orby patients.Causes of ADRsADRs happen for a variety of reasons, some inevitable others, avoidable.Inevitable:Inability to predict with certainty effects of drugsAll drugs have some negative effectsInformation about rare events is, by definition, not likely to be available until after a drugis in extensive useInteractions with other drugs, prescribed or unprescribedIndividual susceptibilityPreventableError in diagnosis13 Directive 2001/83/EC of the Parliament and the Council of 6 November 2001 on the Community CodeRelating to Medicinal Products for Human Use.14 Henman, Professor M. , Minutes, 7 November 2006.18Error in prescription of the drug or the dose including failure to appreciate fullindications, contra indications and risksLack of compliance by patients with professional’s or manufacturer’s instructions as totiming, doses and duration of medication,Self medicationConsequences of ADRs3.3 The consequences of ADRs are significant. In the US it has been estimated that44,000 to 98,000 deaths occur annually as a result of medical error of which about 7,000are attributable to ADRs15. Another US study reported that about 6.7% of patients sufferserious adverse drug effect while in hospital resulting in a fatality rate of 0.32%. In theUS context that translates into 2.2 million serious ADRs in hospitals and 106,000deaths.16 Another US study reports another 350,000 serious adverse events in nursinghomes. The number occurring outside the hospital system is unknown.17Centre for Education &Research on TherapeuticsWhy Learn aboutAdverse Drug Reactions (ADR)?• Over 2 MILLION serious ADRs yearly• 100,000 DEATHS yearly• ADRs 4th leading cause of death ahead of pulmonary diseases, diabetes,AIDS, pneumonia, accidents and automobile deaths15 Committee on Quality of Health Care in America: Institute of Medicine. To err is human: building asafer health system. Washington, D.C.: National Academy Press; 2000.16 Lazarou J, Pomeranz B, Corey PN. Incidence of adverse drug reactions in hospitalized patients: Ameta-analysis of prospective studies. JAMA 1998;279:1200–1205.17 Gurwitz JH, Field TS, Avorn J, McCormick D, Jain S, Eckler M, et al. Incidence and preventability ofadverse drug events in nursing homes. Am J Med 2000;109(2):87–94.19• Ambulatory patients ADR rate - unknown• Nursing home patients ADR rate – 350,000 yearlyInstitute of Medicine, National 2000Lazarou, J. et al JAMA 1998, 279 (15) 1200-1205Gurwitz, J.H. et al Am. J. Med. 2000, 109 (2) 87-94Source: Extract from educational module on ADRs from the FDA Centre for Education and Researchon Therapeutics3.4 Closer to home, a study in the UK of 18,820 admissions to two large generalhospitals found that 6.5% of admissions were due to ADRs. About 4% of bed capacitywas absorbed by these cases and the fatality rate was 0.15%. Most of the reactions weredefinitely or possibly avoidable.18 Surveying the evidence the House of Commons reportconcluded that the cost of ADRs in the UK could run to £ billions per annum.18 Pirmohamed, M. et al. Department of Pharmacology and Therapeutics, University of Liverpool. AdverseDrug Reactions as Cause of Admission to Hospital: Prospective Analysis of 18,820 patients. BMJ. 3 July2004, 329(7456)20Excerpt from Report of Health Committee of the House of Commons“No figures for the economic burden of drug-induced illness yet exist, but it is feared thatit could amount to several billions of pounds per year. The adverse drug reactions, whichaccount for some 3% to 5% of all hospital admissions in the UK, cost in the order of£500 million per year. No estimates have yet been made of the presumably greater cost ofadverse drug reactions which do not lead to hospital treatment at all, nor to thoseexperienced by perhaps 15% of all hospitalised patients. “193.5 No studies of adverse reactions as a whole in the Irish context were brought to theSub-Committee’s attention, though there are some studies which indicate that thesituation is not likely to be much better here than elsewhere. A survey of the literature bypersonnel in the Pharmacoeconomics Centre in St James Hospital reported a study whichidentified prescribing errors of 31.1% for in patients in a Dublin teaching hospital andanother, by the same authors, reported an error rate of 25% in the out patients department.The survey article also reported that two medical insurers calculated that 25% and 19%respectively of claims against GPs in Ireland were for medication errors20. A recentlypublished survey of 600 geriatric patients by staff of the Department of GeriatricMedicine at the Cork University Hospital found that 52% were given inappropriatemedicines. 21 The article does not quantify ADRs as such but the scale of errors suggeststhat the rate may be fairly high.Reporting ADRs3.6 Reporting of ADRs by companies and professionals is essential in order toidentify problems with drugs and to allow the authorities and the industry to formulate19 HOC, page 8.20 Hughes, C., and Barry, M. National Medicines Information Centre Pharmacoeconomics Centre, St JamesHospital, Dublin. Medication Errors, Irish Medical Journal, June 2000, Vol 95, No 4.21 Barry MB, P.J., O’Keefe MB, N., O’Connor MB, K.A. and O’Mahony MD, D.21advice or other actions to prevent these reactions or to mitigate their dangers. Animportant part of this process is the reporting system managed by the Pharmacovigilancesection of the IMB. Under this system (colloquially referred to as the Yellow Cardsystem from the form on which ADRs are reported), ADRs may be filed by doctors,dentists, nurses and pharmacists. This is a spontaneous reporting procedure as distinctfrom the mandatory procedure by which manufacturing or importing companies withlicenses - Marketing Authorisation Holders or MAHs - must report ADRs to their drugsas obtained from clinical trails, post authorisation studies, and those brought to theirattention by professionals. These arrangements are similar to those in use in mostdeveloped countries. At the moment there is no provision for formal reporting of ADRsto the IMB by members of the public though the public can, and frequently does, contactthe IMB informally. These and all other reports are followed up by the IMB.3.7 In Ireland the current rate of reporting of ADRs is as shown below. Reporting ofADRs has increased by about one third in the last five years. This is somewhatless than might have been expected on the basis of the increase in consumption ofmedicines in the same period.Table 6: ADR Reports by SourceMAH1 Clinical Doctors/ Pharma- Nurses TotalTrials Dentists2 Cists32005 856 127 663 105 110 18612004 794 143 604 102 84 17272003 508 306 693 116 38 16612002 673 157 614 134 40 16182001 5444 1604 75 59 22822000 NA 14071 Marketing Authorisation Holders2 General Practitioners, hospital doctors and Community Care doctors3 Community and hospital pharmacists4 Including clinical trials.Source: IMB Annual Reports22Under Reporting3.8 In the opinions of some observers, under reporting is common and a majorweakness with the pharmacovigilance process. Studies from other countries havesuggested that reporting only identifies about 10% of all ADRs. There are a variety ofreasons for under reporting including a tendency by prescribers to think that a givenreaction will have been already noted and reported by someone else. Another factor isuncertainty of the prescriber as to whether the observed reaction is attributable to a drugor if so which one (in the case of those receiving multiple drugs).Excerpt from Evidence from Professor M. HenmanComplacency – belief that only safe drugs are authorisedFear - of becoming involved in litigationGuilt - because a prescribed product has caused harm to the patientAmbition - to collect and publish a series of personal cases which would lead to a delayin reportingIgnorance - of the requirement of reportingDiffidence - about reporting suspicions that might turn out to be unfoundedLethargy – lack of time, of interest, procrastination.223.9 Table 7 below presents an extract from training material on ADRs prepared by theFDA Centre for Research on Therapeutics which firmly rejects erring on the side ofcaution in the reporting of ADRs..Table 7: REPORTING ADRS: PRESCRIBERS’ PERSPECTIVEMisconceptions Reality1) All serious ADRs are documented by thetime a drug is marketed;‘…rare ADRs are usually NOTdocumented by the time a drug ismarketed.’22 Henman, Professor M., Minutes 7 November 2006.232) It can be hard to determine if anindividual drug caused a reaction in apatient receiving multiple medicationsTiming of reaction in relation toprescription and biological plausibility canbe guides. ‘The bottom line is, even whenin doubt about whether a drug caused thereaction, report it.’3) ADRs should only be reported ifabsolute certainty exists that the ADR isrelated to a particular drug‘A health care provider does not have to beabsolutely certain that a drug caused areaction…. ‘All reports contribute to theheightening of the awareness of FDAsafety scientists.’4) One case reported by an individualphysician does not contribute to medicalknowledge‘One individual report CAN make adifference. Many drug withdrawals beganwith one clinical report that initiated furtherinvestigation.’ A single complaint can gainsignificance in the context of results oftrials and other research available toregulatory authorities.Source: Extract from educational module on ADRs from the FDA Centre for Educationand Research in Therapeutics3.10 In most countries, as in Ireland, ADRs are reported by health professionals, butreports from patients direct to the regulatory authorities are not systematicallyencouraged or processed. The reason for this is that without specific knowledge patientsmay not be able to distinguish between symptoms resulting from the medicine they aretaking and those from their environment, lifestyle, or other causes.3.11 It has been submitted that a problem with following up reports of ADRs in Irelandis the difficulty of tracing patients through the primary care and hospital environmentswithout an identifying number. It would seem that several numbering systems are in use:RSI, GMS number and a number assigned by hospitals for each admission. To easilyfollow a report of an ADR, it is necessary to be able to identify treatment administered bydoctors, pharmacies and hospitals and this would be facilitated by a common patientrecord system.2323 Henman, Professor M. Minutes 7 November 2006.243.12 There was some debate among the witnesses as to whether Ireland had a low rateof reporting. Some asserted that Irish rates were low.24 But the IMB reported that theWHO had the previous year noted that the reporting rate in Ireland was among the sevenhighest amongst the 90 countries in the WHO’s reporting system. 25Processing of ADR Reports3.13 Where an ADR is already known to the pharmacovigilance section of the IMB,the report is recorded and the origin (i.e. the professional) is contacted. If the ADR isserious and/or unexpected, the report is evaluated in the IMB and contact is made withthe MAH and the EU and WHO databases are searched for evidence of similar ADRsreported elsewhere.3.14 The practice of the IMB is to encourage professionals to make reports of ADRs.Actions which may follow include:• Changing the SPC to include new side effects;• Making a new contra indication (i.e. circumstance in which the medicine isnot advised);• Adding warnings;• Restricting its use to second line use (i.e. to be used when drugs with knownand milder ADRs or none have not proved successful);• Ordering the withdrawal of the drug.Communication with Prescribers3.15 Once evaluated, any changes resulting have to be advised to the professions. TheIMB does this through:• ‘Drug Safety Newsletter’, a six page newsletter published by the IMB threeor four times a year and distributed to prescribers;• Monthly articles in MIMS (Monthly Index of Medical Specialities), a24 O’Donovan, Dr Orla, Minutes 7 November 200625 Gilvarry, Dr Joan, Minutes 31 October 200625pharmaceutical trade publication of the Irish Medical Times widelycirculated among doctors;• Statements to the media;• In the event of urgent communications, the IMB uses direct mailing andemailing to contact professionals;• The IMB may require MAH’s to communicate with the professions. Suchcommunications must be evaluated and authorised by the IMB.2627IV SUBMISSIONS TO THE SUB-COMMITTEE.Psychiatric Medicines4.1 As noted in paragraph 1.2 there were a total of 17 written submissions and elevenoral presentations by individuals or groups. A substantial number of these weresubmissions comprising reports of ADRs resulting from psychiatric medicationsprescribed for the witnesses themselves, their close relations or their patients. Thesesubmissions made a number of points about these drugs including that:• their use in therapy represents unwarranted medical intervention in what areoften emotional difficulties within the normal range;• though intended for moderate to severe conditions and for relatively shortperiods, some medicines are prescribed for mild conditions and for extendedperiods;• the drugs are often prescribed on the basis of very limited observation of thepatient;• they generate side effects which are misdiagnosed as causal, leading tofurther medication;• the side effects include, behavioural disorders, physical illness, dependence,suicidal ideation and even suicide;• the drugs in question carry inadequate warnings about these side effects;• even where the risks of these side effects are well known they seem not befully appreciated or are ignored by prescribers;• even setting aside the risk of side effects, some of the drugs are of doubtfulbenefit.264.2 Most of the other submissions were from professional organizations andacademics presenting their respective roles in pharmaceutical sector together withobservations, analyses and recommendations. These submissions addressed the questionof ADRs in general rather than in relation to specific patients or drugs.26 O’Mahoney, Nuria and other witnesses, Minutes of 7 November 2006. Fleming, Sean writtensubmission.284.3 The paragraphs which follow summarise the main concerns as contained in thesubmissions or in the publications specifically brought to the Sub-Committee’s attention..Drug Trials4.4 There are shortcomings in the way in which drug trials are carried out andreported such that potential ADRs are not adequately identified. To some extent this isinherent in the process which is inevitably focused on small samples which cannot bewholly representative. The FDA Centre for Education and Research in Therapeuticspoints out that most drugs are approved on the basis of trials on subjects totaling not morethan 1,500. 27 However, it is also contended that the form of drug trials is such that ADRsare likely to be overlooked.28 Indeed, companies can structure tests with that objective inmind29. Furthermore, it is contended that drug companies are not obliged, or do not, makeavailable all studies to regulators.30Regulatory ‘Capture’4.5 Regulatory authorities are under pressures of various kinds from drug companiesby virtue of the economic size and technical resources of the latter. This may result in theauthorities licensing drugs without adequate trials or accepting companies’ researchfindings too readily or not insisting on the dissemination of all available information onpotential ADRs.4.6 Personnel of regulatory agencies are from the same professional background asthe personnel in drug companies. Personnel often move between agencies and companies.There is a high level of interaction. There is always a danger that, in time, regulatorypersonnel may come to share some of the viewpoints of the companies. These influencesare part of the process, identified originally by US political science, as ‘regulatorycapture’.27Training Modules on ADRs by FDA Centre for Education and Research in Therapeutics28 Harlan Krumholz and colleagues. What Have We Learned from Vioxx,. BMJ 5 November 2007. page120.29 Avorn, J. Dangerous Deception – Hiding the Evidence of Adverse Drug Effects. NEJM. 23 November200630 Avorn, J. ibid, HOC page 182294.7 No evidence was submitted to the Sub-Committee that any of the foregoingspecifically affected work of the IMB. However, it was noted that the establishment ofthe IMB was accompanied by a reorientation of priorities of which speedy approval ofindustry applications was an important objective.31 Indeed, the reduction in the backlogof applications from drug companies is one of the first matters referred to by theChairman in the IMB’s latest annual report.32 This does suggest that the tendencies atplay in the larger countries such as the US and UK may be active in Ireland.4.8 Furthermore, as outlined in Section 2 regulation is increasingly an internationalprocess and the IMB is not entirely autonomous in regulating drugs on the Irish market.In this context it was noted that the EU drugs authority, the EMEA, is under the wing ofthe Commission’s Directorate General for Enterprise, not the Directorate General ofHealth and Consumer Affairs.33 The Sub-Committee is uneasy about the priorities whichthis arrangement seems to imply.Reporting ADRs4.9 A number of submissions emphasized underreporting of ADRs. Once drugs havebeen licensed and are in general circulation reporting of ADRs is essential to ensure thatthe manufacturer, the regulatory authorities and the professionals are informed andappropriate action is taken. Manufacturers are obliged to report ADRs but professionalsare not. It is contended that there is inadequate awareness of the need for reporting andfor procedures to encourage reporting. Lack of encouragement for patients to report isregarded is a particular shortcoming of the situation in Ireland. 34Medical Error4.10 Where a drug has been properly licensed and its potential ADRs identified and31 O’Donovan, Dr Orla, Minutes, 7 November 200632 Annual Report, 2005. IMB33 O’Donovan, Dr Orla, Minutes 7 November 200634 O’Donovan, Dr Orla, Minutes 7 November 200630communicated, ADRs may arise at the level of the practitioner by reason of erroneousdiagnosis or prescription. Errors in diagnosis is presumably a matter of training, includingin service training, and is outside the scope of this report. However, ADRs due to errorsin prescribing, although with correct diagnosis, are relevant to the work of the Sub-Committee and are topical given proposals to extend prescribing authority to non doctors.4.11 Errors in prescribing can also occur because the practitioner does not have fullinformation on the patient by virtue of inadequate patient records. Problems also arisebecause of lack of communication between professionals (e.g. hospital doctors and GPs,GPs and community pharmacists).35‘Medicalisation’4.12 ADRs may arise because practitioners have an exaggerated view of the benefit ofthe drugs in relation to its drawbacks. This may be partly attributable to a culture whichassigns untoward confidence in drug therapies. Submissions before the Sub-Committeeemphasized medicalisation of society – the ‘pill for every ill’ syndrome – which promptspractitioners to prescribe (and patients to expect) drugs rather than alternative therapies orno therapy at all. 36Alternatives could include counseling in the case of psychiatric casesand life style changes in the case of cardiac care or obesity. Specific and forcefulcomplaints on these points in relation to psychiatric drugs are noted in paragraph 2.1above.Promotion by Drug Companies4.13 A number of witnesses emphasized the influence of drug companies by reason oftheir economic size and importance, and their promotional activities. Collectively theseinfluence the general climate in favour of drug therapies, as noted above. Promotionalactivity directed at practitioners also inculcates favourable attitudes to drugs in generaland specific drugs in particular. 374.14 Promotion by drug companies to the profession takes a variety of forms including:35 Stewart, Dr Duncan, Written Submission.36 O’Mahoney, Nuria, Minutes 17 October 200637 O’Donovan, Dr Orla, Minutes 6 November 200631• Advertising in professional journals;• Presentations by sales personnel to practitioners;• Funding of research and publication by hospital and academic specialists;• Sponsoring seminars and conferences and payment of expenses andhonoraria to practitioners for lectures, presentations, and other forms ofparticipation;• Ghost writing articles for payment. It is asserted that in the UK 50% ofjournal articles reporting clinical trials are written for the authors by thedrug companies. 384.15 It should be noted that the members of the IPHA subscribe to a code of practiceprescribing high standards of ethical behaviour in relations with, inter alia, the healthprofessions.39 The medical profession also has codes for its members governing conflictsof interest. But this is also true for the UK where, however, the House of Commonsreport noted a number of matters of concern.40 The Sub-Committee has no systematicevidence of questionable practices in Ireland, though members did refer to a number ofwhat seemed like borderline cases. Members feel that there are grounds for concern inthis area.4.16 Direct to advertising to consumers (‘DTCA’) is not permitted in Ireland and themembers of the Sub-Committee were strongly of the view that this should not be changedas it has been in the US and New Zealand. However drug companies do sponsor healthawareness events and publications. Some of these materials are for distribution inschools. These are not explicitly linked to specific drugs but in some cases at least thesponsoring company has a preparation for the illness in question. In any case, it iscontended that there is narrow line between ‘illness awareness’ and ‘diseasemongering.’41 Members expressed concern that the overarching effect of the associationof drug companies with health messages is to confirm in the public mind the importanceof drug therapy.38 HOC, page 5339 Code of Marketing Practice, website of the IPHA40 HOC, page 58, page 10841 HOC, page 10132Reporting of ADRs by Patients4.17 The role of the patient in generating ADRs was also emphasized. Witnessessubmitted that ADRs can arise from:• inappropriate use of OTC drugs;• self medication including purchase of genuine or counterfeit drugs abroad orvia the internet.42• failure to comply with dosing instructions: there are surveys which indicatethat 50% of patients do not fully or at all follow the instructions on theirprescriptions.4342 Pharmaceutical Society of Ireland, written submission43 IPHA, written submission33V CONCLUSIONS AND RECOMMENDATIONS5.1 In this section the Sub-Committee presents some conclusions and a number ofrecommendations. As already emphasised, the Sub-Committee has not been in a positionto conduct an exhaustive study of all of the concerns submitted to it about the role ofpharmaceuticals in medical practice in Ireland today. Consequently, these conclusionsand recommendations should be validated by a more in-depth review. But at this pointthe Sub-Committee believes that the conclusions and recommendations should be on thepublic agenda for discussion and debate.CONCLUSIONS5.2 First, lest it be thought that the Sub-Committee is hostile to drug therapies, thevaluable role which pharmaceuticals have played in the development of modern medicineshould be acknowledged. That pharmaceuticals should continue to have a largecontribution to medicine is not at issue.5.3 However, the influence of the pharmaceuticals industry, and the persuasiveness ofthe promotion of its products is unhealthy and needs to be counterbalanced. In concludingthis the Sub-Committee is not assigning malicious intent to industry personnel, but thepressures on the industry impel it to excessive promotion. The Sub-Committee believesthat this contributes to a generally excessive reliance on drug therapies by the professionsand the public.5.4 The regulatory regime in Ireland confirms to high international standards and thepersonnel of the IMB are highly qualified and professional. However, the Sub-Committeefeels that there are steps which could be taken to improve the strength, independence andtransparency of drug regulation in Ireland.5.5 Notwithstanding concerns about the regulatory process, the Sub-Committee feelsthat the adverse consequences of ADRs – other than those which are inevitable - are morelikely to arise from erroneous use of drugs, which are otherwise safe, than fromregulatory failure. This would point to the need to assign a higher priority topharmacovigilance activities, including reporting of ADRs.5.6 It would also, and this is the Sub-Committee’s other general observation, point up34the need for improvements in pharmacological training, and information systems andmore generally in the delivery of health services, which could mitigate undue reliance ondrugs.RECOMMENDATIONSRegulationFunding5.7 The NDAB was funded by a grant in aid from the Government. The method offunding switched to fees for services to drug companies when the IMB was established.This arrangement by-passes cumbersome budgetary procedures and ensures that fundsare readily available as a function of demands placed on the Board. However, it tends toput the drug companies in the position of clients of the IMB with the inference that theIMB has a corresponding obligation to meet its ‘clients’’ needs. This is not an idealposition for an agency concerned with public safety. The Sub-Committee suggests thatthere would be merit in the Department collecting the fees from the drug companies andconsolidating the receipts into an annual grant to the Board.Trials5.8 Submissions to the Sub-Committee made general references to faults in theregulation of the clinical trials process. The issue was also explored in great detail in theHouse of Commons report. A variety of techniques can be used by companies to showtheir drug in a favourable light.44 The Sub-Committee has not had the time to pursuethese issues in detail. However, it does endorse the recommendation of the House ofCommons report that trials should approximate more closely to conditions in routineclinical settings and should include comparator drugs and non drug approaches.4544 O’Mahoney, N. Minutes, 17 October 2006. HOC, page 50. Krumholz, ibid45 HOC, page 102.355.9 Secondly, the Sub-Committee believes that the licensing process should beginbefore Phase I (FTIM) trials. The Sub-Committee recommends that drug companiesshould submit to the IMB their research programmes and results from the pre-clinicalphase. These files should be sealed, to assure companies of the commercialconfidentiality of their work, and only opened in the event that the companies proceedwith the research to Phase I trials. This would give the IMB a more in-depthunderstanding of the technology when applications are received for the clinical trials.Pharmacovigilance5.10 It has been submitted to the Sub-Committee that an agency which licenses drugsis likely to be compromised to some degree if the drugs which it has licensedsubsequently turn out to be problematic. The failure of the drug might then be seen toreflect badly on the agency’s original decision and lead to some reluctance on the part ofthe agency to come to grips realistically with the problems. The Sub-Committee thereforesuggests that there could be merit in dividing the IMB into two with one agency dealingwith licensing and a second with post marketing surveillance (the pharmacovigilancefunction). This unit would also be involved in training and in promoting procedures incommunity medicine would improve reporting of ADRs.5.11 A major and inevitable weakness of the clinical trials system is that clinicalsamples are much smaller than the target populations who will ultimately receive thelicensed product. Phase IV studies, which follow the drug as it is dispensed through thetarget population are the main means of identifying problems (and efficacy) in the postmarketing phase. Some studies of this type are funded by the drug companies themselvesand occasionally by other – e.g. academic – bodies. But they are not systematicallyundertaken by regulatory authorities. The Sub-Committee recommends that the IMB (orthe post marketing surveillance agency proposed above) should be in a position to fundindependent Phase IV studies if it believes there is insufficient post marketinginformation about specific drugs.46 This research could be carried out in collaborationwith authorities in other countries.46 Avorn, J. ibid36Reporting of Adverse Drug Reactions5.12 The importance of increase reporting of adverse drug reactions was stressed by anumber of witnesses. Reference was made, in particular, to practices in other countriessuch as Denmark, Netherlands and Sweden47, which encourage patients to report adversereactions. The Sub-Committee recommends that the IMB - or the pharmacovigilanceagency should there be one - should increase the volume of publicity targeted atprescribers and pharmacists and start a campaign to inform the public of the need toreport ADRs. At the same time yellow cards should be widely available (e.g. in clinics,pharmacies and health centres). It should be possible also to report ADRs on line to thepharmacovigilance agency or the IMB. Training activities of the IMB in this area mayalso need to be stepped up, especially with the extension of prescribing powers to nursesand para medics.Disease Awareness Advertising by the Pharmaceutical Companies5.13 The Sub-Committee is concerned at the sponsorship of health messages by thedrug companies aimed at specific clinical conditions. The Sub-Committee recognises thatthese messages can have positive effects in public awareness. But while it is appreciatedthat the companies do not promote individual products, the underlying effect may be topromote favourable attitudes of the public towards drug therapies. The Sub-Committeefeels that the Department of Health, in consultation with the Health Promotion Unit(HPU), the IMB and the industry, should endeavour to ensure that these messagesencompass information on non drug therapies. Also, the Department should try to ensurethat taken altogether, the national health priorities are addressed by the HPU and thecompanies.ProfessionTraining5.14 The adequacy of continuing pharmacological education for health professionalsmay need to be reviewed. The high incidence of prescribing errors suggests that some47 Patient Reporting of Adverse Reactions. Outcomes of a Seminar. Health Action International, 26 May2005. Document submitted by Dr Orla O’Donovan.37professionals may not be keeping up to date with fast moving developments in this field.Legislation now under consideration for doctors and pharmacists will give increasedemphasis on continuing education in the future. The Sub-Committee urges that highpriority be given to pharmacological training in this context.5.15 The Sub-Committee is aware that much continuing education for doctors isfunded by drug companies. The Sub-Committee would be concerned if itsrecommendations would lead to an increase in the prominence of the drug companies indoctors’ education. At least where pharmacology is concerned, the Sub-Committee wouldrecommend that funding be from the budget of the Community Health Services.5.16 The House of Commons report specifically recommended that prescribers shouldreceive training in interpretation of trial results and of material distributed bypharmaceutical companies. The Sub-Committee believes this recommendation should beconsidered in this country also.48Conflicts of Interest5.17 The Sub-Committee feels that the potential conflicts of interest created amongdoctors by promotion by pharmaceutical companies need to be addressed andrecommends that the Medical Council review the situation. The House of Commonsrecommend compilation of a register of ‘significant’ benefits received frompharmaceutical companies by medical practitioners. This is worth consideration inIreland.49 ‘Significant’ should be taken to mean anything involving an overnight stay orlong distance travel. Professionals writing articles of presenting lectures should berequired to indicate any financial support received from commercial sources.Formularies5.18 Many new products are launched every year and practitioners are inundated withpromotional materials and activities. Some of this material has genuine informationalvalue. But not all. In addition, there is continuous updating of information on existingdrugs. There is a need for unbiased, independent and practical information on drugs to be48 HOC, page 10749 HOC page 10838available to hospitals and professionals in Ireland. In UK there are a number of sources atnational and local levels. In Ireland the only resources are the Medicines InformationCentre and the Pharmacoeconomics Centre both in St James Hospital. Both of these areoperating at a small scale at the moment. Action needs to be taken to establishformularies at national or regional levels or at the level of groups of generalpractitioners.50Health ServicesInformation Systems5.18 A number of points were made to the Sub-Committee about the availability or useof patient information for improving prescribing practices. The Sub-Committee suggestthat the following should be investigated further:• Creation of systems which enables prescribers to access information on patientsfrom different sources such as hospitals, community medicine or pharmacists. This couldhelpful in avoiding of prescribing errors or ADRs due to drug interractions. It would alsobe useful in facilitating follow up of reports of ADRs 51• Electronic links should be established between hospitals and practitioners andpharmacists ensuring that all sides have full information about common patients;• Exploitation of the data base of the PCRS for macro trends in the consumption fordifferent types of drugs;• Creation and dissemination of computerised decision making systems capable ofscreening for contra indications and drug interactions when prescribers are consideringdrug therapies.52• Dissemination of software, possibly linked to decision making support systems,which permit prescriptions to be printed in order to avoid mistakes caused by spelling orlegibility problems.50 Since drafting of this report commenced, an Irish Medicines Formulary produced by Meridian Irelandhas commenced publication.51 Henman, Professor M. Corry, Dr Michael, written submissions52 One such system is reported under development in Cork University Hospital. Sunday Tribune, 7 January2007, page 1395.19 The Sub-Committee is aware that computerisation is not the panacea that some ITprofessionals suggest or that lay people might like to imagine. There has to be adisposition, and a capacity, on the part of all practitioners to use these systems. Thisshould be ensured by the growing emphasis on continuing medical education. There arealso formidable implementation problems and there may be ethical issues. Nor doescomputer supported decision making remove the need for competence on the part of theprescriber. However, when the cost of medicines and ADRs are considered, evensignificant investment in computerisation and associated training of professionals, wouldseem to be justified on cost grounds alone.Pharmacy5.20 The IPU and PSI made strong cases for enhancing the role of the pharmacist incommunity medicine.53 It seems likely that the pharmacists’ legislation, now underpreparation, will entitle pharmacists to expand their services and responsibilities inprovision of community medicine. The Sub-Committee endorses this trend and urges inparticular that the practice of medication reviews, with the pharmacist as central, shouldbe formalised.Psychological Support Services5.21 A point strongly made by several witnesses and by members of the Sub-Committee themselves is that psychiatric drugs may tend to be prescribed for want of analternative. The patient presenting with symptoms expects some tangible form oftreatment and the practitioner feels under pressure to respond so as, at the minimum, tosend the patient away in a more confident frame of mind. It is in the absence of a fullrange of counselling and psychotherapy services that many medicines, intended formoderate to severe psychiatric disorders, are prescribed for minor symptoms leading insome cases to severe adverse reactions.5.22 The Sub-Committee recommends that there should be an increase in the numberof psychologists and counsellors available in the community health services. This wouldprovide practitioners with an alternative to drug therapy in minor cases and wouldcomplement drug treatment in more serious cases.53 Written submissions. Minutes 31 October 200640The Public5.23 A constant theme of the submissions to the Sub-Committee, and a concern whichthe members share, is the excessive use of medication prescribed by health careprofessionals and excessive use of psychiatric drug therapies in particular. Some of theresponsibility for this lies in the promotional activities of the drug companies and needsto be balanced by a programme of public education on drug use.5.24 The role of the public, including patients, in taking responsibility for andparticipating actively in their own health care is widely recognised. It is the principleunderlying the national Health Promotion Strategy 2000-2005 and the work of the HealthPromotions Unit of the Department of Health. 54 Responsible attitudes to tobacco,alcohol, diet, exercise and sex are important targets of the HPU’s messages. However,taking responsibility for proper use of medical drugs does not figure in the HPU’sagenda. The Sub-Committee believes that establishing a balanced approach to drugtherapy should be an important part of the health promotion strategy and the HPU shouldbe mainly responsible for this change of emphasis.5.25 Therefore, the HPU should by means of messages in the media, distribution ofpublicity material for health centres, pharmacies and its website;• adopt a campaign aimed at informing the public of the appropriate use of drugtherapies so as to reduce patient pressure on practitioners.• Promote an understanding that when a course of drugs is prescribed, it isimportant that it should be completed5.26 Other messages which need to be presented include• That unused drugs should be properly discarded.55 Local DUMP (Disposal ofUnwanted Medicinal Products) campaigns provide the model for a national collaborativeeffort between the HPU and pharmacists.54 website of the Health Promotions Unit55 Irish Pharmaceutical Union, reported that ‘a total of 13 tonnes of medicines have been returned tocommunity pharmacies in the South Western Area Health Board alone since 2003’. Written submission.41• The dangers of counterfeit drugs and self medication5.27 The HPU should collaborate with the pharmacovigilance section of the IMB inpromoting awareness of the possibility of ADRs, the need to report them and the meansof doing so.Patient Safety Agency5.28 A Patient Safety Agency would be the appropriate entity for the implementationof many of the recommendations above. The Sub-Committee therefore recommends thatsuch an entity should be set up. It hopes that the Patient Safety Commission, set up sincethe Sub-Committee started its work, will come to the same conclusion.4243APPENDIX 14445Joint Committee on Health and Children.Order establishing a sub-Committee on the Adverse Side effects ofPharmaceuticals1 Ordered on 12 October:-“Thata)a Sub-Committee (to be called the Sub-Committee on the Adverse Side Effects ofPharmaceuticals) be established to consider such matters as it may think fit inrelation to the adverse side effects of pharmaceuticals.b) the Sub-Committee shall consist of 6 members of whom 3 shall be Members ofDáil Éireann and 3 shall be members of Seanad Éireann;c) the quorom of the sub-Committee shall be 3, of whom 1 at least shall be aMember of Dáil Éireann and 1 a Member of Seanad Éireann;d) in relation to the matter specifically referred to in paragraph a) above, the sub-Committee shall have those functions of the Joint Committee which are set out inparagraphs 2(a)(i) to 2(a)(iii) (Dáil) and in paragraphs1(a)(i) to 1(a)(iii) (Seanad)of the Joint Committee’s Orders of Reference; ande) the Sub-Committee shall have the following powers of the Joint Committee,namely, those contained in Standing Order 81(1), (2) and (4) to (9) (Dáil) and inStanding Order 65(1), (2) and (4) to (9) (Seanad).”4647APPENDIX 24849ORAL SUBMISSIONSDate of AppearanceBefore Sub-CommitteeOganisation Represented WitnessesRonan Quirke, PresidentDr Ambrose McLoughlin,RegistrarPharmaceutical Society ofIreland.Mr Matthew Lynch, AssistantRegistrar10 October 2006Irish PharmaceuticalHealthcare AssociationJohn McLoughlin, PresidentAnne Nolan, Chief ExecutiveDr John Stinson, MedicalDirectorMs Leonie Clarke,ConsultantNuria O’MahoneyDr Michael CorryBasil MillerMind Freedom John McCarthyMind Freedom Mary Maddock17 October 2006Gregory WhitePat O’Mahoney, ChiefExecutiveDr. Joan Gilvarry, Director ofHuman Medicine,Irish Medicine BoardDr Brendan Buckley,Chairman AdvisoryCommittee for Human HealthLiz Hoctor, Vice PresidentSeamus Feely, SecretaryGeneralDarragh O’Loughlin,Treasurer31 October 2006The Irish PharmaceuticalsUnionPamela Logan, Professional& Business Manager,50Dr. Orla O’Sullivan,Dept. of Applied SocialStudies,UCC and HealthAction International7 NovemberMartin Henman, Co.Ordinator of the Centre forthe Practice of Pharmacy,Trinity College, Dublin 251APPENDIX 35253Members of theJoint Committee on Health and ChildrenDeputies: Paudge Connolly TD (Ind)Beverly Flynn (Ind)Jimmy Devins (FF) (Vice-Chair)Dermot Fitzpatrick (FF)John Gormley (GP)Liz McManus (Lab)John Moloney (FF) (Chair)Dan Neville (FG)Charlie O’Connor (FF) (Government Convenor)Fiona O’Malley (PD)Liam Twomey (FG)Senators: Fergal Browne (FG) (Opposition Convenor)Geraldine Feeney (FF)Camillus Glynn (FF)Mary Henry (Ind)Chairman: Mr John Moloney (FF)Clerk: Ms. Gina Long5455Members of the Sub-Committee onThe Adverse Side Effects of PharmaceuticalsDeputies: Paudge Connolly (Ind) ChairmanJimmy Devins (FF)Liam Twomey (FG)Senators: Camillus Glynn (FF)Mary Henry (Ind)Geraldine Feeney (FF)Clerk: Ms. Gina Long

ouTube - Can Antidepressants Cause Violence?

Dr. Moria Dolan, Executive Director for the Medical Accountability Network discusses the link between antidepressants medications and suicide, violence and ...www.youtube.com/watch?v=OyPuE314SDQ - 116k - Cached - Similar pages - Note this