Clinical trials for better health policies

©Mario Beauregard/Fotolia.com

A recent OECD Recommendation on the Governance of Clinical Trials issued in December 2012 could improve the outlook for fighting deadly diseases around the world. Here is how.

Chronic myelogenous leukemia (CML) is a rare cancer that affects the bone marrow. Until ten years ago, a diagnosis of CML was a death sentence unless you had a tissue-matched donor, usually a sibling, and underwent a bone marrow transplant. In 1996, laboratory scientists showed that a drug selectively killed CML cells in culture without harming normal cells. Two years later, the first reports of 31 patients treated with this drug were published; all had dramatic responses.

This impressive progress changed the outlook for these patients, and it could not have been made without clinical trials. And with life expectancy rising around the world, but haunted by the prospect of substantial disability, such clinical trials are likely to become more important in the years ahead. But they are not without their challenges.

Recently the OECD adopted a policy initiative on the governance of clinical trials in an attempt to define a new framework for better oversight of clinical trials, with a special emphasis on facilitating those trials that have public and charitable rather than industry funders.* Why was the instrument adopted and what can it help to achieve?

A tale of two studies

Clinical trials are rigorously designed experiments in which participants who have consented to receive a new therapy or to be assigned randomly to one of several possible treatments are carefully studied for the positive and negative effects of those therapies. The aim is to provide sufficient evidence to guide medical practice and public health policy. Clinical trials are a critical step for the production of new drugs and for the study of existing health treatments. They improve the health and quality of life of our citizens, add value to our economies, and guide policymakers responsible for laws and regulations. This benefit applies to both common and rare diseases.

Take the promising results related to CML again. Over the subsequent five years, multiple studies confirmed the efficacy of the drug, now called Gleevec™. In 2013, bone marrow transplantation is rarely required for patients with CML, whose extended survival is expected. How did this happen? University medical scientists supported by US taxpayer funds from the National Institutes of Health (NIH) worked with a pharmaceutical company, Novartis, to take this drug from the shelf to the clinic. Now patients all over the world receive Gleevec™. Its approval came about because of rigorously conducted clinical trials in which participants with CML agreed to receive an experimental, untested drug. They took significant risks because no one knew whether the drug would work or have bad side effects. Later trials have included Gleevec™ as one of multiple therapies; participants are taking much less risk because the effects of the drugs are now well-known. But because CML is rare, international studies were essential to carry out the test on enough patients to get significant results.

More common diseases also benefit from clinical trials. About the same time that Gleevec™ studies began, 3,234 healthy people at high risk of developing type 2 diabetes agreed to take part in a clinical trial to see if their diabetes could be prevented. A third of the patients had no treatment, a third received an approved marketed anti-diabetes drug called metformin, and the remaining third were put on diet and exercise programmes. Four years later, the people who changed their diet and took exercise were found to be only half as likely to develop diabetes as those with no treatment. Metformin reduced the likelihood of developing diabetes, but also provided less benefit than diet and exercise. The study was funded by US taxpayers and conducted at 27 different sites.

Worldwide, about 370 million people have type 2 diabetes; the WHO estimates that this will rise to 552 million by 2030. Could the results of the US study apply elsewhere, in Germany and the UK, or India and South Africa, for instance? Clinical trials in these countries could help us find out.

The question is, how can we harmonise approaches and better compare results for better policies? Every country has laws and regulations governing the conduct of clinical trials. Following the Second World War, all nations adopted some basic principles to guide the ethical conduct of research. International guidelines are detailed in the Nuremberg Code and the Declaration of Helsinki, while many countries have additional reports, such as the Belmont Report in the US, that outline common principles (see references). These are codified and implemented differently in different countries and regions, but the common principles apply in all countries.

While research studies may pose risks to participants, failure to conduct research poses much greater risks to citizens everywhere. Examples of treatments introduced without enough evidence include thalidomide, which caused disastrous birth defects in infants when given to pregnant women; administration of high doses of oxygen to premature infants with consequent blindness; and the use first of radical mastectomy and, later, of bone marrow transplantation for breast cancer, with major toxicity and no benefit.

Because of differences in laws and regulations, there are often barriers to conducting international research. Regulations designed to assign responsibility for protection of participants and ensure accountability may hinder collaboration. Not all clinical trials pose similar risks to participants. Treatments that are untested may create significant risks to participants and liability for sponsors. In contrast, trials of established therapies (as in the case of the diabetes study described above) pose little or no risk to participants. Existing regulatory systems often have similar administrative requirements whatever the risk, and sponsor liability may be significant.

What is the new OECD Recommendation about? Health care systems and clinical research infrastructure vary widely, especially between high income and lower income countries. Many policy barriers to conducting international trials may exist, many deriving from inconsistencies in definitions, assignment of responsibilities and requirements for oversight. The OECD initiative is a major step towards developing a harmonised framework for the governance of clinical trials. It introduces a risk-based oversight and management methodology, which combines risk categories based on the marketing authorisation status of the medical product with a trial-specific approach that considers issues such as the type of populations involved in a trial, and the informed consent of the patients.

In other words, besides facilitating the conduct of international trials, the implementation of the OECD Recommendation helps to streamline procedures for low-risk trials, while at the same time strengthening the protection of the patients, increasing the quality of the data and improving the credibility of the results. It also addresses the thorny challenge of seeking an accepted method for assessing the risk that participants face in entering a trial, and hence the responsibility borne by the study sponsor for compensation and care of participants affected by the study.

In this together

In December 2012, The Lancet published an entire issue on the Global Burden of Disease Study, demonstrating improved life expectancy with substantial disability for the last decade in most countries. Neither the quality of life nor our global economy can afford to continue these trends.

Indeed, science, health care and disease are now shared globally. Biomedical research is resource-intensive. Evidence gathered in one country is used in others, sometimes without adequate study. Especially for diseases in which large numbers of participants and locations are needed to answer scientific questions with statistical validity, international studies are essential. In rare diseases, it is impossible to do studies in single countries. An outstanding example is the development of arsenic trioxide for acute promyelocytic leukemia, a treatment discovered in China, studied worldwide and now benefiting patients on every continent. Regardless of economic resources, all countries should participate in joint scientific enterprises to ensure maximal benefit.

The OECD recommendations are designed to facilitate collaboration, leverage existing investments, and enable all nations to improve the health of their citizens and economies, enhancing technological development while prolonging healthier, more productive, lives.

References

The 2012 OECD Recommendation on the Governance of Clinical Trials and its explanatory memorandum can be found at www.oecd.org/sti/sci-tech/oecd-recommendation-governance-of-clinical-trials.pdf

See www.oecd.org/health

The Lancet 2012), The Global Burden of Disease Study 2010, December 13

National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (NCPHSBBR) (1979), “The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research”

“The Nuremberg Code”(1949), Trials of War Criminals before the Nuremberg Military Tribunals Under Control Council Law No. 10, Vol. 2, pp. 181–182, US Government Printing Office, Washington

World Medical Association (WMA) (1964/2008), “The Declaration of Helsinki”

©OECD Observer No 294 Q1 2013




Economic data

GDP growth: +0.6% Q4 2017 year-on-year
Consumer price inflation: 2.3% Apr 2018 annual
Trade: +2.7% exp, +3.0% imp, Q4 2017
Unemployment: 5.4% Mar 2018
Last update: 06 Jun 2018

E-Newsletter

Stay up-to-date with the latest news from the OECD by signing up for our e-newsletter :

Twitter feed

Suscribe now

<b>Subscribe now!</b>

To receive your exclusive paper editions delivered to you directly


Online edition
Previous editions

Don't miss

  • Watch the webcast of the final press conference of the OECD annual ministerial meeting 2018.
  • International co-operation, inclusive growth and digitalisation lead the themes of the 2018 OECD Forum in Paris on 29-30 May, under the banner of What brings us together www.oecd.org/forum. It is held alongside the annual OECD Ministerial Council Meeting on 30-31 May, chaired this year by France with a focus on multilateralism www.oecd.org/mcm.
  • Listen to the "Robots are coming for our jobs" episode of The Guardian's "Chips with Everything podcast", in which The Guardian’s economics editor, Larry Elliott, and Jeremy Wyatt, a professor of robotics and artificial intelligence at the University of Birmingham, and Jordan Erica Webber, freelance journalist, discuss the findings of the new OECD report "Automation, skills use and training". Listen here.
  • Do we really know the difference between right and wrong? Alison Taylor of BSR and Susan Hawley of Corruption Watch tell us why it matters to play by the rules. Watch the recording of our Facebook live interview here.
  • Has public decision-making been hijacked by a privileged few? Watch the recording of our Facebook live interview with Stav Shaffir, MK (Zionist Union) Chair of the Knesset Committee on Transparency here.
  • Can a nudge help us make more ethical decisions? Watch the recording of our Facebook live interview with Saugatto Datta, managing director at ideas42 here.
  • Ambassador Aleksander Surdej, Permanent Representative of Poland to the OECD, was a guest on France 24’s English-language show “The Debate”, where he discussed French President Emmanuel Macron’s speech at the World Economic Forum in Davos.
  • The fight against tax evasion is gaining further momentum as Barbados, Côte d’Ivoire, Jamaica, Malaysia, Panama and Tunisia signed the BEPS Multilateral Convention on 24 January, bringing the total number of signatories to 78. The Convention strengthens existing tax treaties and reduces opportunities for tax avoidance by multinational enterprises.
  • Rousseau
  • Do you trust your government? The OECD’s How's life 2017 report finds that only 38% of people in OECD countries trust their government. How can we improve our old "Social contract?" Read more.
  • Papers show “past coming back to haunt us”: OECD Secretary-General Angel Gurria tells Sky News that the so-called "Paradise Papers" show a past coming back to haunt us, but one which is now being dismantled. Please watch the video.
  • When someone asks me to describe an ideal girl, in my head, she is a person who is physically and mentally independent, brave to speak her mind, treated with respect just like she treats others, and inspiring to herself and others. But I know that the reality is still so much different. By Alda, 18, on International Day of the Girl. Read more.
  • Globalisation’s many benefits have been unequally shared, and public policy has struggled to keep up with a rapidly-shifting world. The OECD is working alongside governments and international organisations to help improve and harness the gains while tackling the root causes of inequality, and ensuring a level playing field globally. Please watch.
  • Read some of the insightful remarks made at OECD Forum 2017, held on 6-7 June. OECD Forum kick-started events with a focus on inclusive growth, digitalisation, and trust, under the overall theme of Bridging Divides.
  • Checking out the job situation with the OECD scoreboard of labour market performances: do you want to know how your country compares with neighbours and competitors on income levels or employment?
  • Trade is an important point of focus in today’s international economy. This video presents facts and statistics from OECD’s most recent publications on this topic.
  • The OECD Gender Initiative examines existing barriers to gender equality in education, employment, and entrepreneurship. The gender portal monitors the progress made by governments to promote gender equality in both OECD and non-OECD countries and provides good practices based on analytical tools and reliable data.
  • Interested in a career in Paris at the OECD? The OECD is a major international organisation, with a mission to build better policies for better lives. With our hub based in one of the world's global cities and offices across continents, find out more at www.oecd.org/careers .
  • Visit the OECD Gender Data Portal. Selected indicators shedding light on gender inequalities in education, employment and entrepreneurship.

Most Popular Articles

OECD Insights Blog

NOTE: All signed articles in the OECD Observer express the opinions of the authors
and do not necessarily represent the official views of OECD member countries.

All rights reserved. OECD 2018