製薬会社自身による薬剤効果の検証は利益相反となるか(2/3) Vincent Lawton

BMJがBen GoldacreVincent Lawtonによる製薬業界の実験の利益相反についての対論を掲載した。

Ben Goldacreは製薬会社が行う実験は利益相反になっていて、医療判断を狂わせる"悪い証拠"が作られているという立場から、Vincent Lawtonは適切に対処すれば、そうはならないという立場から論を展開して、対論を形成している。

前回はBen Goldacreの論を読んだので、今日は Vincent Lawtonの論から:
Vincent Lawton: "Is the conflict of interest unacceptable when drug companies conduct trials on their own drugs? No", BMJ 2009;339:b4953, doi: 10.1136/bmj.b4953, 2009

The drug industry is sometimes accused of finding it difficult to reconcile the difference between the strict disciplines of ethical science and its responsibility to its shareholders to return a healthy profit. Proposals to move control of this critical process in drug development into the hands of an "objective" third party need to be critically examined. Clinical trials are properly managed by a rigorous system of regulatory scrutiny throughout. Potential for conflict of interest, when clearly identified and controlled, is not unacceptable.


The industry develops medicines through years of painstaking research by some of the best scientists in the world, often in collaboration with academic researchers. Clinical trials are an essential part of developing safe and effective drugs, and after the drug is introduced to clinical use more is discovered about its effects. Further trials, which can involve academic collaboration, are done to provide further information and study whether new indications can be added to the drug’s use -- for example, as in the landmark 4S trial.1


Trial designs and protocols are assessed and endorsed by regulators2 who assiduously guard against inadequate trial design, insist on good clinical practice standards,3 and ensure high quality analyses. Ethics committees, who are fully independent (normally established and funded by the NHS in the UK through health authorities), do not countenance a substandard study design.4 They frequently intervene before a study is allowed to proceed. An impartial data monitoring committee (funded by the trial sponsor)5, comprising distinguished academic clinicians, monitors the analyses and trial results and protects the safety of participants, the credibility of the study, and the validity of results. Indeed, some evidence suggests that industry sponsored studies have higher methodological quality than those funded by other bodies 6.


No system is perfect, so it is important to keep enhancing the safeguards. To eliminate bias, the industry has developed various transparency measures. Companies often design studies with the input of regulatory agencies and the academic community. No matter how the study is designed, it cannot start until approval has been granted from both the regulatory bodies (the US Food and Drugs Administration and the European Medicines Agency) and the independent ethics committees,7 The analyses and methods must be in place and agreed by the regulatory agencies before the trial begins.

いかなる制度も完全ではないので、保証手段を強化し続けることは重要である。バイアスを除去するために、製薬業界は透明性を高める様々な手段を開発してきた。製薬会社はしばしば規制当局と学術界からのデータなどから研究デザインをつくっている。そして、研究がどうデザインされていようとも、規制当局(米国FDAとEuropean Medicines Agency)の許可と、独立倫理委員会の承認なしに、研究は始められない。試験開始前には、分析および試験方法が適切でなければならず、規制当局の同意がなければならない。

Trials not conducted by drug companies can and do deviate from these standards. For example, the Women’s Health Initiative study in 2002 was conducted by National Institutes of Health sponsored investigators and looked at effects of hormone replacement therapy.8 The original focus of the study was coronary heart disease, but the investigators found that breast cancer -- which had a low incidence, leading to results that were not statistically significant -- got more media attention. The significance level was, therefore, changed post hoc in order to re-focus on breast cancer, causing alarm in concerned women.

製薬会社によるものでない臨床試験はこれらの基準に合わない可能性があり、実際に合致していない例もある。たとえば、2002年にWomen's Health Initiativeの研究が、NIHの資金で行われ、ホルモン補充療法の効果を調査した。研究のもともとの焦点は冠状動脈性心臓病だったが、発生確率が低く、統計的に有意でない乳癌にメディアの関心が集まった。乳癌を研究対象とするために後付けで有意水準が変更され、結果として不安に思う女性たちに警告を発することになった。

Open access to clinical trial information is becoming increasingly important to policy makers, healthcare professionals, patients, and the general public. The drug industry actively worked to change the public’s negative perception of clinical research and their lack of trust in science, which is directly related to the lack of clear information freely available to them. In January 2005,9 the major drug industry trade associations from Europe, Japan, and the United States announced their commitment to increase the transparency of clinical trials sponsored by their member companies. The commitment was for the industry to register its trials in central, publicly accessible databases. Most major companies also publish trial data, whether positive or negative, on their own websites. The databases usually have data on registered medicines, which are available in at least one country. However, companies or academics may judge that trial results for an investigational product that has failed in development have substantial medical importance. In such cases, study sponsors are encouraged, principally by the trade associations, to publish these results too. Data are intended to be published no later than a year after the medicine is first approved, although a backlog exists.10 The International Federation of Pharmaceutical Manufacturers and Associations has recently updated its position on disclosure of clinical trial information.11 This extends the range of trials that member companies should provide information on to include all clinical trials in patients, as a minimum. The scope of this new joint position will include early stage safety trials of medicines for life threatening conditions, which are usually done in healthy volunteers.

臨床試験の情報へのオープンアクセスは政策立案者・健康保健の専門家・患者・一般市民にとって、ますます重要となっている。製薬業界は臨床研究に対する市民の否定的な認識および科学への不信を改めるために、積極的に行動した。それらは、自由に市民が利用できる明確な情報が不足していることに直接関連している。2005年1月に、欧州・日本・米国の主要な製薬業界団体が、団体加盟企業の資金による臨床試験の透明性を高めることを約束する発表を行った。これは、製薬会社が臨床試験結果を、ひとつの公的にアクセスできるデータベースに登録することを約束するものだった。肯定的あるいは否定的であろうとも、大半の大手製薬会社は自らのウェブサイトで公開している。データベースには少なくとも一カ国で登録された薬品に関するデータがある。しかし、製薬会社や学術研究機関は失敗した開発薬品の試験結果を、医学的に重要だと判断するかもしれない。そのような場合、業界団体は研究の資金提供者に対して、原則的には、それらのデータも公開するよう推奨している。データは薬品が承認されてから1年以内に公開することが求められているが、バックログも残っている。"The International Federation of Pharmaceutical Manufacturers and Associations"は最近、臨床試験情報の公開についての立場を更新した。これは最低限として、患者に対する臨床試験すべての情報を加盟会社が公開する試験の範囲を拡大するものである。この新しい立場では、通常は健康なボランティアによって行われる、生命の危険性についての薬品安全性試験の初期段階も公開対象としている。

The notion that a super cadre of publicly sponsored academic researchers would be capable of conducting all clinical trials on all new medicines, leading to regulatory approval, requires a stretch of the imagination. Even assuming it was possible, it would take many years and enormous cost to establish an infrastructure to conduct these trials. Furthermore, academic investigators sometimes report drug adverse events less comprehensively than drug companies 12


Having invested an average of $1.2bn (£724m, €802m) and 10 years to bring a medicine to the market, is the drug industry expected to surrender its intellectual property? A third party’s lack of infrastructure, expertise, and resources would inevitably lead to delays, cutting into patient access and the patent life of the medicine. This seems to be a sure way to drive away the incentive to innovate.13 At present about 75% of the funding for clinical trials in the United States comes from industry14 and total industry spending on research is greater than that of the National Institutes of Health.12


The better way for patients, health care, and innovation is to continuously improve what we have, despite potential competing interests. Competition and investment drive innovation and are dependent on the right environment. Companies should continue to work closely with academia and regulators to identify weaknesses or shortcomings and find ways to address them. Appropriate safeguards of transparency, scientific integrity, and regulation should ensure that different interests do not become unacceptably conflicted.



  • Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994;344:1383-9.[CrossRef][Web of Science][Medline]
  • O’Donnell P. EMEA and FDA team up on GCP. Applied Clinical Trials Online 2009 Sept 1. http://appliedclinicaltrialsonline.findpharma.com/appliedclinicaltrials/article/articleDetail.jsp?id=624938.
  • Medicines and Healthcare Products Regulatory Agency. Good clinical practice. 2009. www.mhra.gov.uk/Howweregulate/Medicines/Inspectionandstandards/GoodClinicalPractice/index.htm.
    Privireal. Research ethics committees?countries. 2009. www.privireal.org/content/rec/countries.php.
  • Ellenberg S, Fleming TR, DeMets DL. Data monitoring committees in clinical trials: a practical perspective (statistics in practice). John Wiley and Sons; 2003.
  • Lexchin J, Bero LA, Djulbegovic B, Clark O. Pharmaceutical industry sponsorship and research outcome and quality: systematic review. BMJ 2003;326:1167-70.[Abstract/Free Full Text]
  • Piribo. Drug approval trends at the FDA and EMEA: process improvements, heightened scrutiny and industry response. Piribo, 2008.
  • Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. JAMA 2002;288:321-33.[Abstract/Free Full Text]
  • Joint position on the disclosure of clinical trial information via clinical trial registries and databases. Updated November 2008. www.ifpma.org/clinicaltrials.
  • Lee K, Bacchetti P, Sim I. Publication of clinical trials supporting successful new drug applications: a literature analysis. PLoS Med 2008;5:e191.[CrossRef][Medline]
  • Joint position on the disclosure of clinical trial information via clinical trial registries and databases. Updated 10 November 2009. www.ifpma.org/clinicaltrials.
  • Jatoi A, Nguyen PL. Side effects and pharmaceutical company bias: adverse event reporting in cancer supportive and palliative care trials. Expert Opin Investig Drugs 2008;17:1787-90.[CrossRef][Web of Science][Medline]
    Kealey T. The economic laws of scientific research. Macmillan Press, 1996.
  • Chopra SS. Industry funding of clinical trials: benefit or bias? JAMA;290:113-4.

  • posted by Kumicit at 2010/01/27 07:15 | Comment(0) | TrackBack(0) | Others | このブログの読者になる | 更新情報をチェックする



    コメント: [必須入力]