Product information past perfect

The Medical Journal of Australia ISSN: 0025729X 15 January 2007 186 2 51-52 ©The Medical Journal of Australia 2007 www.mja.com.au Editorials o not rely on the Australian approved product information for up-to-date advice about drug therapy. This seems to be the main message of Stockigt’s review of entries for thyroid disease in prescribing references, which are based on the product information supplied for each drug (page 76). In some cases the information was so out of date, its recommendations were potentially harmful. While these findings will not surprise everyone, many health professionals will be disturbed to know that they cannot completely trust the product information approved by the Therapeutic Goods Administration (TGA). It is often the source that people turn to when seeking detailed drug information. As the product information also underpins consumer medicines information and sets the boundaries for advertising, flaws could have far-reaching consequences. The Therapeutic Goods Act 1989 (Cwlth) has little to say about product information other than it relates to “the safe and effective use of the goods, including information regarding the usefulness and limitations of the goods”. Details about what should be in the document are contained in the Australian regulatory guidelines for prescription medicines. These guidelines do not state that the product information should be kept up to date. When a sponsor company applies to have a new drug registered in Australia, it supplies a draft of the product information. This is scrutinised by the TGA and the Australian Drug Evaluation Committee to check that the information reflects the evidence supporting the drug’s safety and efficacy. Although the sponsor can make safety-related notifications, the product information cannot be changed after registration without the TGA’s approval. At the time of registration, the accuracy of the product information is at its zenith; however, it may soon be outdated. With the pressure to approve drugs quickly, new information is likely to emerge after the product is marketed. Some drugs seem to be approved mainly on the results of phase II trials. Their product information will therefore need updating when the results of phase III trials become available. Adverse effects may only emerge after marketing. A review in the United States of 548 new drugs found that more than 10% later acquired a “blackbox” warning about serious adverse effects or were withdrawn. While major safety concerns are likely to trigger an update of the product information, less prominent problems may be overlooked. In Australia, the sponsor is responsible for keeping the information up to date. How seriously this responsibility is taken is unclear. Updating product information, particularly about old and possibly less profitable products, and disseminating the changes may not be a top corporate priority. The TGA also has to set priorities. It has limited resources but many areas of regulatory responsibility, including complementary medicines. While the TGA was once government-funded, it now has to recover all its costs in fees and charges. Having the regulator funded by fees from the industry it regulates may have disadvantages. Industry probably prefers to pay the TGA to register new drugs, than to dust off the product information of old drugs. To manage within its resources the TGA has adopted a “risk management approach” to regulation. Activities with a low risk of adverse outcomes receive less scrutiny. This is why complementary medicines are not evaluated before they are listed in the Australian Register of Therapeutic Goods. Similarly, the TGA’s risk analysis may not identify the product information of old drugs as a high risk. Many old drugs only have brief product information. This may not have been updated for years and it can be difficult to know its currency. The date of approval at the end of the document reflects the most recent change. However, this change may have been a minor variation rather than a rigorous review. Perhaps there is a need for a “use-by date”. Drugs have an expiry date, so why not extend the concept to product information? This would require a date to be set for a comprehensive check of the product information. Such reviews would be more frequent early in the product’s life to ensure emerging data were included. For older products the reviews could be less frequent, but at least there would be a mechanism for checking that the information was not obsolete. This could be an opportunity for specialist societies to assist the TGA with updating. Regularly reviewing product information would require greater resources for the TGA. As the TGA can charge for changes to the product information, the mechanism exists to recover the additional costs. (Changes to the product information involving the evaluation of data currently cost about $4000.) Although an agreement between the TGA and industry to keep product information up to date seems sensible, there are likely to be commercial objections. The TGA’s philosophy is to regulate while “freeing industry from any unnecessary regulatory burden”. Most corporations aim to cut costs, so it is possible that a company may withdraw an old drug rather than be forced to review the product information and then pay to have it approved. In 2005, the TGA circulated a discussion paper on improving access to information about prescription medicines. This contained several suggestions for greater use of electronic methods to make up-to-date product information easily available. The outcome of this discussion is currently unknown. Would a recommendation to update the product information regularly be accepted in a business environment focused on new products, cost containment and reduced regulation?