Collaboration in Research Protocol

© 2009 Palgrave Macmillan 1745-7904 Journal of Medical Marketing Vol. 9, 3, 213–220

www.palgrave-journals.com/jmm/

Correspondence: Deborah Richards Gilead Sciences Pty Limited, Level 1, 128 Jolimont Road, East Melbourne, VIC 3002, Australia E-mail: [email protected]

Original Article

Collaboration in research protocol design: A case study exploring knowledge creation for the pharmaceutical industry and prescribing physicians Received (in revised form): 28 th June 2009

Deborah Richards is currently employed by Gilead Sciences in the research and development department. She has over 10 years experience within the pharmaceutical industry in clinical research and medical information roles. This research was conducted as part of a Master ’ s degree, which was completed before joining Gilead Sciences. The views expressed in this publication are not necessarily those of Deborah ’ s existing employers.

Brad Dalton is Managing Director of medScript, a medical communication agency that supplies the Australian healthcare industry with a range of communication and advisory board management services. He acts as a consultant to several private and not-for-profi t organisations. Brad is also a lecturer in the School of Human Life Sciences at the University of Tasmania. He is responsible for undergraduate teaching in the areas of anatomy, physiology, pathophysiology and pharmacology to students in nursing, biomedical science, health science and human movement studies.

ABSTRACT The pharmaceutical industry is under increasing pressure to bring innovative products to market in a timely manner. Without access to information from people outside the industry, this task is more diffi cult. Because physicians may have a greater understanding of specifi c product benefi ts in a clinical setting, knowledge creation within the pharmaceutical industry can be facilitated through active physician participation in clinical trial design, thereby delivering more effective use of medicines. Ultimately, knowledge creation efforts may enhance the use of evidence-based decision making and improve professional practice, which in turn will promote innovation in service and product development. The study aims to examine the potential for knowledge creation through collaboration between physicians and industry representatives. Eight physicians specialising in a specifi c disease agreed to meet with three industry representatives who organise clinical trials. The primary endpoint for this study was to design a phase IV clinical trial with collaborating physicians that specifi cally addressed a medical need within a highly specialised area of medicine. After meeting with industry representatives, the physicians concluded that company-sponsored studies were not appropriate, and any potential research should be conducted on a small scale (pilot and exploratory) within a clinical setting. The collaboration formed in this study failed to produce the intended result of a phase IV research protocol. Physicians were, however, able to steer the industry representatives towards research sponsorship that would – in their opinion – best serve the interests of improved patient outcomes. These fi ndings

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INTRODUCTION Phase I / IIIa research protocols are fundamental for securing regulatory approval and reimbursement of new drugs. Protocols for phase I / IIIa clinical trials sponsored by pharmaceutical companies are often developed internally, usually by head offi ce staff. Regulatory agencies and physicians may comment on aspects of these protocols to ensure that they will address key effi cacy and safety issues and are in line with current practice. 1 However, local physician involvement is often limited to patient recruitment. In contrast, phase IIIb / IV research protocols tend to address issues that are not considered critical for drug registration, including additional health outcomes information and / or pricing and reimbursement data that might support market access negotiations. This frequently involves gathering information on how safe and / or effective a drug is over time, in a ‘ real-world ’ setting. Ultimately, phase IIIb / IV research protocols allow physicians to gain better appreciation for the effi cacy of a drug in their specifi c practice and with their particular patients. 2

As limited public funds are available for drug research, physicians will often design research protocols (investigator initiated studies (IISs)), and then approach the appropriate pharmaceutical company for sponsorship. 1 This dynamic partnership between academia and industry has many benefi ts. Some IIS provide unique insights into potential new applications for a drug, whereas industry provides the tools with which to convert these fi ndings to practical application. A recent industry benchmarking study conducted in

Australia showed that in 2008, pharmaceutical companies spent AU $ 34 950 000 on phase IV studies and $ 16 750 000 on IIS. 3

However, physician ’ s interest in IISs and subsequent support from the pharmaceutical industry depend on a variety of factors. When considering funding for phase IV trials, pharmaceutical companies may focus on aligning the hypothesised outcomes with product marketing strategy and less on advancing medical knowledge. For this reason, physicians may elect to work independently on their own research. This ‘ non-collaborative ’ or ‘ ideological divide ’ approach to developing later phase research protocols may reduce the amount of research that could potentially be conducted.

Collaboration is critical to the future success of research. Working in collaboration may assist industry by enabling faster decision making and avoiding duplicate research. 4 Collaborations can also create opportunities for knowledge sharing. Physicians and pharmaceutical companies may come to better understand each other ’ s needs, resulting in a more tailored approach towards ongoing product development. From an organisational perspective, obtaining information from sources outside the company that can be used to generate new knowledge within the organisation presents a signifi cant challenge. 5 However, the ability to convert physician knowledge into focused strategies is critical to the successful uptake and utilisation of products. 6

Relatively little is published about the potential for knowledge creation between

support the importance of knowledge creation through collaboration between physicians and pharmaceutical companies. Journal of Medical Marketing (2009) 9, 213–220. doi: 10.1057/jmm.2009.20; published online 24 July 2009

Keywords: Knowledge creation ; pharmaceutical industry ; physician ; collaboration

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Collaboration in research protocol design


physicians and the pharmaceutical industry. Therefore, the aim of this study was to address the following issues. First, whether physicians and industry representatives can collaborate to create a clinical trial protocol of mutual benefi t and interest. Second, whether this collaboration can create knowledge that industry representatives can then use to enhance the quality use of a particular medicine.

METHODOLOGY This study used an action research approach, which involves a system of enquiry that includes planning, action and refl ection. 7 This involves establishing a framework of ideas that are incorporated into a methodology used to investigate an area of concern or interest. This process is cyclic and allows for feedback. This feedback allows changes to the operating plan during the course of the study. 7 This methodology was chosen because action outcomes focused on improved practice and knowledge generation can be achieved through a research process. The process is participative or collaborative and allows for critical refl ection and refi nement of ideas as each cycle progresses. Action research in general can provide an immediate solution to a problem while also informing theory. This can also be repeated by others to further advance the theory.

The framework of ideas for this study included the following. First, pharmaceutical companies conduct phase IV research because it can increase quality use of a specifi c medicine. 2 Second, physicians engage in research that is clinically relevant and aims to produce meaningful patient outcomes. 1 Third, as pharmaceutical companies also desire to develop and market medications that improve patient outcomes, physicians and industry have similar goals. Accordingly, physicians and industry representatives

could work collaboratively to design a research protocol that has meaningful patient outcomes. 8 Finally, this collaboration may result in knowledge creation within the pharmaceutical company, which could be used to further enhance quality use of a specifi c medicine (desired outcome).

The operating plan for this study involved establishing a collaborative group to develop a phase IV research protocol to improve the treatment of a specifi c disease. Medical personnel from a mid-sized pharmaceutical company invited physicians with expertise in a specifi c area of medicine from different parts of Australia to form an advisory board. Invitations were provided on the basis of hospital position (for example, department head), and through searches of online medical databases of physicians publishing in the fi eld. Two physicians from each major tertiary hospital in Australia, where the majority of operations to treat the disease in question are performed, were invited to participate. At least one physician from each hospital held the position of Director. The relevant medical representative from the patient advocacy body for the disease was also invited. Nineteen physicians were invited and eight were able to attend, ensuring each state and the patient advocacy body were represented.

Three industry representatives from the pharmaceutical company, an external facilitator and a medical writer also attended the meeting. The industry representatives were responsible for developing phase IIIb / IV research protocols and ongoing product development to enhance quality use of the medicine. The facilitator was hired to ensure that discussion was open and honest, and meeting objectives were met. The industry representatives actively participated in the meeting and detailed meeting minutes were captured. The

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medical writer prepared a literature review detailing research fi ndings of studies on the disease. This review was distributed to all advisory board participants 2 weeks before the meeting, and included copies of all cited publications.

An agenda was created for a face-to-face meeting at the beginning of the study. The meeting objectives were to review clinical data relating to the disease, to identify research gaps and to propose clinically relevant research questions. The desired outcomes of the meeting were to develop research question(s) for further exploration in a company-sponsored phase IV study, and the creation of a small group to act as a protocol steering committee. Workshops were held during the meeting that encouraged participants to:

share expectations of the advisory board and study participation, as a basis for review at the end of the meeting; identify and score (relative weighting) general characteristics of an ‘ excellent ’ study and study protocol; review gaps in the knowledge base for treatment of the disease and clinical practice; identify and develop proposed research questions to address gaps in the knowledge base; prioritise proposed research questions, using weightings derived in the previous session; and agree on subsequent steps in protocol development, identify ‘ working party ’ membership and required ongoing communications within the group.

Minutes were recorded from the fi rst and subsequent meetings. The minutes were analysed to identify new knowledge created as part of the collaborative process that would potentially add value to the organisation and improve the use of the specifi c medicine. All requirements for

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advisory board conduct detailed in the Medicines Australia Code of Conduct, edition 15, were adhered to. 9

Feedback through an online questionnaire was also sought from participants about individual perceptions of the collaborative approach in terms of the value placed on this type of interaction and physician ’ s role in the development of research protocols. Of particular interest was feedback on knowledge sharing that did or did not occur during meetings, and the value, or lack thereof, placed on such a collaborative approach to protocol development. It was anticipated that this feedback could then be used to improve the collaborative process to further advance knowledge creation.

RESULTS

Knowledge creation At the beginning of the advisory board, the physicians were asked about their expectations and desired outcomes of the meeting and phase IV research protocols. Physicians expressed curiosity about formulating a suitable research question and a desire to generate evidence to support and / or improve clinical practice. They identifi ed a need for meaningful, clinically important outcomes and the opportunity to improve their understanding of the disease process. By participating in study design, the physicians recognised their potential to infl uence the outcome of future studies by identifying more / less appropriate treatment regimens and study endpoints. They indicated that they wish to infl uence how patients are recruited for studies (for example, active involvement of advocacy groups). They reported a desire to infl uence study design to ensure that the design is ethical from a clinical standpoint. They wanted to ensure that realistic questions are asked in

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pharmaceutical-sponsored studies, such as whether drug supply would continue after a research trial concluded, particularly if the indication of interest was not funded under the pharmaceutical benefi ts scheme. They also suggested that any phase IIIb / IV clinical trial should acknowledge the clinical context in which it is run, without disadvantaging the control group.

The participating physicians identifi ed a number of important factors that would infl uence their decision to participate in future trials ( Table 1 ). The physicians listed both positive and negative factors. Among these factors, the clinical impact of the research question was rated as most important, whereas adequate funding was ranked as least important ( Table 2 ).

After lengthy discussion, the group could not identify gaps in the knowledge base relating to the disease that could form the basis of a new research protocol. The group decided that additional information about the disease status before any treatment modality is considered would help to evaluate the potential for a suitable research question. This information would also help to determine whether the area of medicine in question is a genuine problem requiring a solution. Most physicians keep such information hospital databases, but do not share this

data because no central database exists. Group members subsequently extracted this information in their own time, from their hospital databases, and actively shared the data. An additional meeting was arranged to further discuss possible research questions and study endpoints in light of this new shared knowledge. The fi nal outcome of the teleconference was that there were no unanswered questions, and creating a research protocol could be a ‘ waste ’ of research funding for the pharmaceutical company. Comments from participants included ‘ Mortality and morbidity is what really matters and this requires a long-term study ’ , and ‘ From the data we provided, the disease status is not really an issue ’ that requires active research.

Despite these fi ndings, participating physicians acknowledged that some unanswered questions may exist that could form the basis of a research protocol,

Table 1 : Factors infl uencing physicians ’ decision to participate in pharmaceutical company-sponsored research protocols

Transparency of the clinical trial process Receive adequate funds Studies should be educative, as are investigator meetings and advisory boards Direct company involvement is preferred compared to the use of third parties (for example, Contract Research

Organisations) Clinical studies should improve the intensity of patient management Answer interesting questions (novel, clinically important, resulting in a change in clinical practice) Study design should consider patient burden Studies should generate patient enthusiasm Marketing studies should be avoided unless they answer clinically relevant questions Comprehensive, well-written documentation that is fl exible to individual concerns Simplistic protocols with realistic primary endpoints It is essential that trial results are published in a reputable journal Not only the question but also its implementation should be feasible Effi cient data management A pre-specifi ed plan / timeline for data management, reporting and write up is essential

Table 2 : Physicians ’ assessment of the fi ve most important factors associated with phase IV research protocols

1. Interesting question with clinical impact. 2. Takes the patient burden into consideration. 3. Feasibility of question – simplicity of endpoint /

realistic endpoints. 4. Data management that avoids third party

involvement. 5. Adequate budget.

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although this work is exploratory in nature and might best be conducted within the clinical setting on a small scale. In this case, the pharmaceutical company could create grant funding to enable this research to occur independently within the clinical research setting.

Using their own knowledge of the disease and current treatment options, the physicians outlined fi ve important ideas for small-scale projects investigating further treatment options. These ideas focused on both early and late phases of the disease process, key endpoints to evaluate and areas of current uncertainty.

DISCUSSION The aim of this research was to explore the potential for physicians and industry representatives to collaborate and create clinical trial protocols of mutual benefi t and interest. Also of interest was whether this collaboration could create knowledge that the pharmaceutical company could then use to increase quality use of the medicine in question. Discussion and information sharing helped the physicians to formulate fi ve ideas for future small-scale research.

The physicians agreed to share their own knowledge with industry representatives to achieve a research protocol that was clinically relevant. The physicians agreed to collaborate because they believed that they can positively infl uence the relevance of future research and ensure that the outcomes foster improved patient care. Furthermore, the physicians believed that they introduced an element of ‘ realism ’ into study designs. This observation suggests that physicians believe that protocols designed without their input may lack clinical signifi cance, and are perhaps more focused on the specifi c objectives of the sponsoring company. Aitken contends that physicians are primarily motivated to participate in research to enhance patient care and

deliver public benefi ts. 10 In contrast, the main incentive for pharmaceutical companies to participate in research is to develop products in a timely fashion that will increase fi nancial return and shareholder value. 10 In this study, physicians and industry representatives were able to overcome these differing motives and collaborate to develop a research protocol that could satisfy both parties. Bodenheimer 11 asserts that despite company sponsored trials being ‘ tainted by the profi t incentive, they do contain the potential for balance between the commercial interests of industry and the scientifi c goals of investigators ’ . The ‘ scientifi c ’ goals asserted by the physicians involved in this collaboration were associated with ensuring the potential of the outcomes were to improve patient care.

Linking research to action is essential in the clinical trial process. 12 If physicians can incorporate research fi ndings into clinical practice, then the pharmaceutical company could benefi t from appropriate increased use of their product, thus creating a ‘ balance ’ in outcomes and supporting the concept of quality use of medicines. Not only can physicians introduce clinical relevance into research protocols, they can also provide valuable, experienced-based knowledge about patient treatment patterns.

Physicians in this study shared information stored on internal databases to fi ll a gap in existing knowledge about the disease and current treatment patterns. This information proved critical for formulating new research ideas that (a) may not have otherwise been considered and (b) might provide clinically relevant, patient-focussed outcomes. They concluded that a pharmaceutical-sponsored study was not appropriate, and any potential research should be conducted on a small clinical setting. This was not the intended outcome of the meeting. However, the pharmaceutical company

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involved could have spent approximately $ 1 million / year on a project that the physicians might not have considered important if this knowledge was not available or the collaboration was not formed. To meet this alternative need, the pharmaceutical company could support several small, independent research protocols by grants. This approach may create an opportunity for ongoing dialogue that, in turn, could form the basis of future collaboration between the physicians and the company. This collaboration could then create a shared context for future knowledge exchange.

Tacit physician knowledge, whether it is information stored on personal databases or information based upon personal experience, is a potential source of information for pharmaceutical companies to create knowledge that otherwise does not exist within their own organisations. The pharmaceutical industry is under increasing pressure to bring innovative products to market in a timely manner. 13 Without access to information from individuals outside the industry, this task is all the more diffi cult. To prosper and continue to create innovative products, organisations must learn from ‘ outside ’ information. 5

The fl ow of information into the pharmaceutical industry depends upon physicians interacting with industry. The importance of obtaining external input from those with current knowledge and skills should be to challenge internal norms and assumptions. 14 This type of feedback could enable those working internally to incorporate new information and revise existing assumptions. In terms of product development, this approach could assist with creating new products or modifying existing products to increase appropriate product uptake. Physician input into research design could also facilitate improved use of medicines because physicians may have a greater

understanding of the product benefi ts (developed early through involvement in research design). Such collaboration throughout the product lifecycle could see greater alignment between pharmaceutical company and physician goals. In this manner, the joint vision or shared context is improved patient outcomes.

In this study, interaction between physicians the pharmaceutical company formed the basis for knowledge creation. Knowledge creation is not an individually focused process; it has a collective and collaborative focus. 15 In this study, a group of physicians with the common concern came together with industry representatives who also had a similar concern. As part of the process, new knowledge was created through interaction. Indeed, increased interaction between interested groups will have the greatest impact on knowledge creation. 15 The results of this study support this view from the perspective of physician – industry interactions.

Several limitations of this study are worth discussing. First, this study involved a small number of physicians working in a highly specialised area of medicine. As this area of medicine deals closely with immediate life and death circumstances, there may be greater emphasis and interest around research protocols. Secondly, it should be noted that it is often a self-selecting group of physicians that become involved in these types of collaborative efforts. Consequently, the physicians selected in our study may be more open to working with industry to develop research protocols than physicians working in other areas of medicine. Lastly, a lack of publications about knowledge creation between physicians and the pharmaceutical industry make the results diffi cult to compare and generalise. Despite these limitations, this study highlights the benefi ts that are possible when successful collaborations are formed.

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In conclusion, this research showed that physicians were willing to collaborate with industry to create a research protocol. Interaction between the physicians and industry representatives was successful for creating new knowledge. A key component of knowledge creation was that the physicians shared tacit knowledge. Both physicians and industry representatives could ultimately use this knowledge to improve patient care by increasing the quality use of a specifi c medicine.

REFERENCES 1 Yamada , T . ( 2005 ) Academia-industry collaboration:

A dynamic partnership on behalf of patients . Journal of Clinical Investigations 115 : 2944 – 2947 .

2 Glass , H . ( 2003 ) Physician participation in market support clinical studies and subsequent prescribing behavior . Journal of Pharmaceutical Marketing and Management 15 (4) : 3 – 16 .

3 Pharmaceuticals Industry Council . ( 2009 ) R & D taskforce 2009 forum: The future in context , http://www.pharmacouncil.com.au/resources.php , accessed 7 April 2009 .

4 Malek , J . and Breggar , M . ( 2001 ) The new R & D paradigm . Pharmaceutical Executive 21 (2) : 78 – 86 .

5 Drucker , P . F . ( 2002 ) Managing in the Next Society . Oxford: Butterworth-Heinemann .

6 Murtaugh , T . , Furey , D . and Steen , R . ( 2002 ) What marketers want . Pharmaceutical Executive 12 : 90 – 96 .

7 Checkland , P . and Holwell , S . ( 1998 ) Action research: Its nature and validity . Systemic Practice and Action Research 11 (1) : 9 – 21 .

8 Duvall , D . ( 2006 ) Confl ict of interest or ideological divide: The need for ongoing collaboration between physicians and industry . Current Medical Research and Opinion 22 : 1807 – 1812 .

9 Medicines Australia . ( 2007 ) Code of Conduct , 15th edn. Canberra. Medicines Australia .

10 Aiken , P . and Katona , C . ( 2006 ) Working with the drug industry – is your reputation at risk? BMJ Careers 330 (7488) : 73 – 75 .

11 Bodenheimer , T . ( 2000 ) Uneasy alliance: Clinical investigators and the pharmaceutical industry . The New England Journal of Medicine 342 : 1539 – 1544 .

12 Nuyens , Y . and Lansang , M . A . ( 2006 ) Knowledge translation: Linking the past to the future . Bulletin of the World Health Organization 84 (8) : 590 .

13 Cacciotti , J . and Shew , B . ( 2006 ) Pharma’s next top model: Slimmer business models . Pharmaceutical Executive 26 (3) : 82 – 86 .

14 Buchel , B . ( 2007 ) Knowledge creation and transfer; from team to the whole organization . In: K. Ichijo and I. Nonaka (eds.) Knowledge Creation and Management New Challenges for Managers . New York: Oxford University Press .

15 Allee , V . ( 2003 ) The Future of Knowledge: Increasing Prosperity Through the Value of Networks . Burlington, VT: Elsevier .

Collaboration in Research Protocol

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