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Digital Pharma: Pharmacovigilance, the internet and social media

pharmafile | June 15, 2011 | Feature | Medical Communications, Research and Development, Sales and Marketing | Digital Pharma blog, adverse event reporting, adverse events, pharmacovigilance

This week the ABPI released guidance on managing adverse events from social media and the internet in a document that suggests a series of best practices for the area and was shared with the MHRA prior to publication.

Here, in a guest blog post, the ABPI’s Pharmacovigilance Expert Network argues that the current pharmacovigilance legislative framework is unsuitable for today’s digital era and calls for support from pharma industry professionals to place it higher on the agenda.

The internet has changed the way society manages health. We look up symptoms on Wikipedia and NHS Choices, blog about illnesses, discuss conditions and side-effects on websites such as PatientsLikeMe and discuss health issues with Facebook friends.

An estimated 80% of internet users search for health information on-line, making it the third most popular online pursuit after e-mail and using a search engine. Imperial College research found that 70% of UK patients use the internet to search for health information with a third deciding not to visit their general practitioner afterwards. The explosion of user-generated content has potentially created a plethora of safety information (including information on off-label use, misuse and normal clinical practice prescription habits) that due to lack of a robust legislative framework is currently not being sufficiently accessed, analysed or even considered by the relevant stakeholders involved in public health.

Traditional methods of reporting suspected adverse drug reactions (e.g. the MHRA Yellow Card scheme) are an important pharmacovigilance tool. However, today’s array of blogs, tweets and on-line medical communities affords us alternative sources of potentially important safety information which, if accessed and analysed appropriately, can compliment traditional methodology.

The current legislative situation does not support Marketing Authorisation Holders (MAHs) in fulfilling their obligation to collect and analyse all safety data they become aware of and has, to some extent, led to the pharmaceutical industry shying away from ‘non-company sponsored websites’ (see below for definitions). The ABPI Pharmacovigilance Expert Network (PEN) has become increasingly concerned that the complex regulatory requirements for pharmacovigilance, brought in to protect patients at a time of information scarcity, are now acting as a barrier to the use of this information as an important additional resource to protect public health.

To address this contradiction, the ABPI PEN has a vision of how MAHs can utilise safety data from the internet and call upon regulators to consider different regulatory approaches.

Pharmaceutical company sponsored websites

‘Pharmaceutical company sponsored websites’ can be important sources of safety information and designed to facilitate the pharmacovigilance process. For example, sites can provide links or access to internal/external reporting based tools or include free text fields, which allow the public to report suspected adverse drug reactions. Other components such as the “Terms and Conditions for Use” or a formal site registration process can be utilised to obtain information that enables MAHs to identify and contact users in order to validate and follow-up on safety information. A moderation process can be implemented which allows companies to define moderation activities which would include actions to be taken in response to safety information being posted. Finally blogging policies, ‘netiquettes’ and disclaimers can also be utilised. These features and processes allow companies to have a high degree of control over how safety information generated on pharmaceutical company sponsored sites is managed.

Pharmaceutical companies must comply with the ABPI Code of Practice and the PMCPA has recently issued guidance for the industry on digital communications.

The ABPI’s PEN recognises the value to MAHs in using pharmaceutical company sponsored websites (and especially social media channels) to communicate with its external customers. It acknowledges that these channels can generate safety information over which the company has a high degree of control (albeit that the data can be highly variable in terms of volume and quality). In addition, the new European legislation on pharmacovigilance calls for increased participation by patients and consumers in the pharmacovigilance process and company sponsored websites may prove to be useful tools to this end. However, it is essential to ensure that company monitoring activities for company sponsored sites are proportionate to public health benefit. As an industry we need to provide evidence to regulators that a risk-based approach may be warranted in certain situations and we must work together with the relevant stakeholders to devise appropriate methodologies to facilitate this risk based approach.

Non-pharmaceutical company sponsored websites

There are multiple reasons why pharmacovigilance data arising from non-company sponsored websites is different from company sponsored websites. Firstly, it is almost impossible to validate or follow-up with the individual who generated the information (follow-up may be necessary to obtain additional information relevant to the evaluation of the case). This is especially true for many on-line healthcare discussion communities who discourage the use of personally identifiable information (e.g. name, phone number, e-mail address or website URL). Even where information exists, some sites prohibit businesses from participating and/or using the information in any way and this makes follow-up impossible. We believe there is a need to discuss the ethics of attempting follow-up at all on data posted on non-company sponsored websites as these individuals do not specifically intend to report suspected adverse drug reactions. In fact, if an individual posts an adverse event for a generic medicine (e.g. ibuprofen) on a public forum then multiple follow-up requests may be made. Put simply, the current rules for follow-up are not appropriate for this platform.

Secondly, individuals are often just “talking” to one another with no intention to report a suspected adverse drug reaction and the safety information they generate (on an individual case basis) is often vague with little detail.

Thirdly, pharmacovigilance advisory group CIOMS V suggests that there is no obligation to report adverse events from secondary care databases (e.g. the General Practice Research Database) as the information does not originate from defined projects (e.g. clinical trials, market research, patient support programmes) and can be generated by multiple individuals for various reasons and uses. The ABPI PEN believe that this risk extends to non-company sponsored sites. There is a very real risk of duplicate reporting (if companies were obligated to collect and expedite individual reports from such sources) as MAHs would not know how the data has been used previously or how many times the data may appear on-line.

Pharmacovigilance data from non-pharmaceutical company sponsored sites should not be ignored, but it is unique and must be treated differently. A new regulatory strategy must be found that will enable the use of this data pragmatically, focusing on the key outcome of improving medicine safety and away from rigid regulatory reporting requirements.

The ABPI PEN proposes that companies should have no routine obligation to collect and follow-up on individual adverse events arising from non-pharmaceutical company sponsored websites. Data from this channel is best treated as an adjunct to conventional sources. MAHs and regulators should therefore work harmoniously to adopt a more scientific approach to aggregate analysis of this data to help generate or confirm potential signals. Consistent with the scientific approach, the methodology used must be devised as appropriate to the medicinal product and the data and not mandated by a legislative framework. The rationale for an examination of non-company sponsored data should be recorded in a document that can be produced during a pharmacovigilance inspection or in a Pharmacovigilance Plan/Risk Management Plan, as appropriate.

We need to harness technological advances to benefit public health by tapping into the high volume of near real time data to give us an insight into how medicines are used and tolerated in the real-world shortly after product launch. The speed at which potential signals could be generated and evaluated is likely to be much quicker than traditional methods.

The use of social media sites as a tool to measure the effectiveness of any risk minimisation activities should also be explored as should utilising such forums for safety alerts.

Conclusion

Pharmacovigilance processes and their regulations need to be innovative to meet the challenge of utilising relevant safety data from the rapidly expanding pool of information generated from the internet. There is a short window of opportunity to influence the upcoming European pharmacovigilance good practice guidance, due in July 2012, and ensure the most is made of the resources now at our disposal to protect public health.

DOWNLOAD: Guidance notes on the management of adverse events and product complaints from pharmaceutical company sponsored websites from the ABPI’s website

The ABPI’s Pharmacovigilance Expert Network is made up of representatives from the Association’s membership of UK pharmaceutical companies

Please send any comments or feedback on the issues highlighted in this article or the guidance notes to Esteban Herrero-Martinez at abpiregulatory@abpi.org.uk.

Definitions:

A website is considered to be pharmaceutical-company sponsored if the site is owned, paid for and controlled by the pharmaceutical company. Control means that the company has authority over the final content.

A website is considered to be non-pharmaceutical company sponsored if the site is NOT owned, paid for and controlled by the company. For such a site, there must be no possibility that the pharmaceutical company has been able to control the final content of the site. A donation (financial or otherwise) to an organisation/site by a pharmaceutical company does not constitute ownership provided that the pharmaceutical company does not control the final content of the site.

A pharmaceutical company may choose to sponsor a “page” on a website/platform that they do not own (e.g. a company Facebook page). If the company has control over the content of the sponsored page then this is considered to be pharmaceutical-company sponsored. The rest of the site/platform is considered to be non-company sponsored.

Dominic Tyer is web editor for Pharmafocus and InPharm.com and the author of the Digital Pharma blog He can be contacted via email, Twitter or LinkedIn.