Bulletin Index/

Safety and the Precautionary Principle

1. Safety First: Women and Health Protection

2. Hormone Therapy: Health Protection Lessons from the Women’s Health Initiative

3. Registering the Impact of Breast Implants

4. Women and Adverse Drug Reactions: Reporting in the Canadian Context

Public Health vs. Profit

5. Direct-to-Consumer Advertising of Prescription Drugs – Whatever the Problem, You Can Always Pop a Pill

6. International Harmonisation of New Drugs Regulation: Not in Women’s Best Interest

7. Communicating about Environmental Risks and Infant Feeding

8. Canadian Women’s Health Network

Lessons from the Past - Ongoing Risks

9. Beyond DES – Hormones in the Environment

10. DES Action Canada

11. The Over-Prescription of Benzodiazepines

International Harmonisation of New Drugs Regulation: Not in Women’s Best Interest

Women and Health Protection, based on a paper by John Abraham, Professor, Centre for Research in Health and Medicine, University of Sussex, Brighton

For the last 12 years, a pharmaceutical industry/government organization called the International Conference on Harmonisation of Technical Requirements (ICH) has been working to blend the approval process for new pharmaceutical drugs from Europe, the United States, and Japan, into one set of standards. This would reduce development costs, reduce the time to get drugs to market, and thereby assure greater profits. If the rush to "harmonise" to the lowest of existing standards leads to compromises in safety standards, there is good reason to be concerned.

Harmonisation of pharmaceutical regulation has important implications for public health, not just for the pharmaceutical marketplace. If public health were the priority, an International Conference on Harmonisation would differ substantially from the current ICH process. For a start, national governments and the WHO would be voting members, and the international and regional industry associations would be observers. Currently ICH operates in the opposite manner—it is chaired by the international brand-name industry association (IFPMA). The harmonisation should be reformulated into an open, accountable, and democratic process.

While not a voting member, Health Canada has adopted the vast majority of ICH guidelines through regulatory change.[1] There was no public debate, in Parliament or more widely, about Canada’s adoption of ICH guidelines. Yet they will have a direct impact on the safety standards used by Health Canada when it approves new medicine and, unless proposed ICH standards for clinical trials are changed, a potentially negative impact on women’s health.

Women and ICH
ICH proposals completely ignore the need for special research guidelines for women. Women use more medicines than men and are vulnerable in different ways. Women have also been disproportionately affected by some of the major drug disasters in the past that could have been prevented through better regulations, such as DES (diethylstilbestrol).[2] And women are still disproportionately affected: eight of the ten prescription drugs withdrawn for safety reasons from the US market between 1997 and 2001 affected more women than men.[3]

A key requirement of any new medication is that it must be effective and safe in treating the condition for which it was designed and for all of the populations that will be using it. The ICH created detailed guidelines for companies on ensuring ethnic representation, geriatric representation, and pediatric standards.[4] It is therefore imperative that:

• The ICH creates a Working Group on Women, using U.S. and Canadian guidelines as a starting point.



• ICH member companies be mandated to enroll women in all clinical trials of drugs that will be used by women, in numbers sufficient to be able to separately assess drug effectiveness, safety, side effects, and dosage levels for women as compared to men. Government regulators, such as Health Canada, should ensure that adequate monitoring and enforcement of these guidelines take place.

A "Special" Population
Women have historically been underrepresented in drug research trials for fear that if they are, or become pregnant, the drug could cause birth defects in the child to be born. It is now recognized that women of childbearing age need not be excluded from research as long as they are using effective birth control methods. Enough women should be involved in all stages of drug development so that safety and efficacy can be analyzed separately for them. Results from male-only studies cannot be generalized for many reasons, including the following:

• On average, women are smaller than men. Most serious side effects are thought to be dose related. When women take dosages designed only for men they are possibly getting a higher dose than may be safe. There is no mechanism in place to ensure that such trials include separate analyses in women to see if the drug works differently, so that appropriate dosage can be determined.



• Some drugs have adverse effects that women are known to be biologically more prone to than men, including cardiac effects like QT interval prolongation (abnormal cardiac rhythm).[5]



• Several drugs are known to be metabolized at different rates for women than men or are eliminated from the body in different ways. This can also affect the dosage women should be prescribed.



• On average, women use different combinations of medications than men; hence drug interactions that might occur in women will not be picked up if they are not analyzed separately.



• While women of childbearing age are now more routinely included in clinical trials, not enough are included in order to separately analyze the data.

To read about the wide range of public health concerns related to ICH and a detailed list of recommendations to protect public safety in relation to the ICH proposals, see the brochure, Who Benefits? International Harmonisation of the Regulation of New Pharmaceutical Drugs (in French and English), and the article, International Harmonisation of Pharmaceuticals: Key Issues of Concern for Public Health, at  http://www.whp-apsf.ca.

Women and Health Protection
Web site: www.whp-apsf.ca
E-mail: info@whp-apsf.ca

NOTES

[1] For a complete list of documents from the Therapeutic Products Directorate (Health Canada) on the adoption of ICH guidelines, go to: http://www.hc-sc.gc.ca/hpb-dgps/therapeut/htmleng/guide_ich.html.

[2] See DES Action Canada on page 20 of the Research Bulletin.

[3] Heinrich J. Director Health Care-Public Health Issues. US General Accounting Office. Drug Safety: Most Drugs Withdrawn in Recent Years Had Greater Health Risks for Women. GAO-01-286R; Drugs Withdrawn from Market. Letter to: Harkin T, OJ Snowe, US Senate and HA Waxman, House of Representatives. January 19, 2001.

[4] Ethnic Factors in the Acceptability of Foreign Clinical Data, ICH, 1998; Studies in Support of Special Populations: Geriatrics, ICH, 1993; and Clinical Investigation of Medicinal Products in the Pediatric Population, ICH, 2000. For further information see ICH website, http://www.ifpma.org/ich1.html.

[5] Heinrich, 2001.

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