and Morals

Pre-trial obligations

(1) Convene an independent ethics advisory board

(2) Confirm individual trials are properly funded and devise contingency plans if needed

(3) Assess how potential financial failure might harm stakeholders outside the company and devise plans to insulate them from the identified harms

Intra-trial obligations

(4) Be vigilant for signs of impending financial problems

(5) Refrain from hype as an investigational product enters a clinical trial

Obligations if the research has been abandoned for financial reasons

(6) Fulfill obligations to patients and researchers. Transfer data and disseminate results

Obligations of non-corporate stakeholders

(7) Review and approve protocols based on a collective, patient-centered ethic

10.1 Pre-trial Obligations

  • (Recommendation 1)Convene an independent ethics advisory board.

Given the novelty and ethical sensitivity surrounding the use of hESC’s, it is interesting to note that, while Geron began its hESC program with ethics advice, it is unclear whether such advice was sought when the human research was started or when the research was abandoned (Eaton 2004).4 Nonetheless, many biomedical companies, understanding the ethical complexity of their work, have incorporated ethics into their decision-making. Geron Bio-Med’s Chief Executive Officer Simon Best recognized the need for ethics advice when he said, “We in the industry are not experts in ethics . Forming an ethics advisory board to deal with both scientific discoveries and the conduct of business is therefore a strategic and moral necessity” (Brower 2002). This statement is a recognition that ethics advisory boards (EABs) can play an important role in assisting companies to ensure that safeguards for stakeholders are in place before human trials begin (Eaton 2007). In addition, EABs can expand their usefulness by assisting companies in executing their obligations in the event that a trial ends prematurely.

Specific to our main concern, EABs should examine whether the financial commitment, resources, and track record exist for a company to complete a planned trial. Financial experts can be appointed to the EAB to assist this deliberation. The language of informed consent should also be clear about the risk of stopping a trial for all reasonably foreseeable causes, including economic. Also, the consent should describe the consequences, plans, and funding for follow-up care if the trial ends prematurely. Any clause signaling the right of the sponsor to discontinue any study for any reasons at any time should be eliminated.

  • (Recommendation 2) Ensure individual trials are properly funded.

An objective, good faith analysis of the ability to fund a trial to completion is required. Sponsors certainly plan for financial success and strive to guard against losses from unsuccessful clinical programs, but they should also design trials within the company’s means and plan for any reasonably foreseeable financial contingencies that may require abandoning the trial. These include avoiding overly optimistic cost and time projections, lack of sufficient funds, unrealistic faith in the ability to raise money during the trial, emerging competing products that would make this product obsolete or inadequate, and inability to meet milestone requirements of a major funder of the research. If any of these factors pose a significant risk of financial failure, the company should re-consider proceeding and devise contingency plans to better assure successful study completion. We note the likelihood that clinical research will cost more and/or take longer to complete when the therapeutic in question is novel, unique, or associated with ethical or political controversy, thereby increasing the difficulty of making these determinations. We also note that novel therapeutics associated with significant scientific concern that first-in-human research is premature also have a higher likelihood of failure.

  • (Recommendation 3) Assess how potential financial failure might harm stakeholders outside the company and devise plans to insulate them from the identified harms.

After an investigation of the likely consequences, informed consents should reveal to subjects and stakeholders any significant risk of abandonment for financial reasons. Patients and researchers should be told not just that the company reserves the right to abandon the trial, but that there is a risk of this particular kind of failure and the consequences that may result. If it is likely that the subjects will have ongoing medical needs after the research has been stopped, the company could consider funding a trust to pay for the costs of that future medical treatment. If these medical needs stem from exposure to a unique or first-in-human therapeutic, the company may want to identify and/or train those physicians best placed to provide competent care for the subjects. These measures can promote confidence in human volunteers and researchers and improve the willingness to participate in clinical trials.

Sponsors should also decide in advance what it would do to preserve the data and the technology if the company steps away, providing that both retain their value to society. Investigating opportunities for sale, transfer, and/or license of the intellectual property rights should be a component of this obligation. A commitment to publish the results should be made if the trial ends prematurely or if the program is abandoned.

Once the company has assured itself that it has a good faith belief that it can fund the trial to completion and that protective contingencies are in place, managers need to make a commitment to finish the trial in order to prevent the harms discussed here. If the company cannot assure itself of these factors, it should not initiate the trial.

10.2 Intra-trial Obligations

  • (Recommendation 4) Be vigilant for signs of impending financial problems.

It is by no means a given that markets have the same optimism in the research progress as does the company conducting it. Neither should the company assume that there is an unending appetite to fund the company’s continuing research. Early detection of signs that the funding will run out should lead the company to execute contingency plans in the event that market forces impede trial progress. Such plans may take the form of the identification of better-funded research partners, co-licensing technology, or merger with another company in the same financial sector.

  • (Recommendation 5) Refrain from hype as a product enters a clinical trial.

Companies are always motivated to project an optimistic view of their technology, since shareholders, investors, and the marketplace value the start of an approved clinical trial. During product development, companies use optimism to drive shareholder value and raise money. They reason, correctly, that any indication that a research program is in trouble destroys value.

However, overly optimistic statements are unfairly misleading and unethical. Inflating the promise of the investigational product can also induce patients to unwisely volunteer for the research and as such violate moral norms of protecting the vulnerable (Goodin 1998; Hawkins and Emanuel 2008). Even if optimistic statements result in the infusion of capital investments, values will plunge when unembellished research data emerge or studies are abandoned.

10.3 Obligations if the Research Has Been Abandoned for Financial Reasons

  • (Recommendation 6) Fulfill obligations to patients and researchers. Transfer data and disseminate results.

If the company has taken reasonable steps in advance to address this possibility, mitigating the resultant harm will be much less problematic. Prior commitments to subjects and researchers can be fulfilled, the protocols can be transferred if possible, the data disclosed, and the intellectual property made available to others who have the capability of making use of it.