Page 370 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

348 PART III Therapeutic Modalities for the Cancer Patient

genetic approaches that may uncover oncogenic pathways and • BOX 18.1 Suggested “Elements of Consent” to

targets more easily and inform discovery and application of per- Include in Informed Client Consent
sonalized medicine strategies.
VetBooks.ir 1. Purpose of research
Documents
Clinical Trial Ethics
2. Expected duration of participation
There are key ethical standards employed in clinical trial design, 3. Description of procedures
and the goal of all clinicians is to ensure standards are met when 4. Possible discomforts and risks
offering a trial to a client or enrolling a patient within a clini- 5. Possible benefits
cal trial. Many clinical trials provide partially or fully funded 6. Alternative treatment (or alternative to participation)
care for eligible pets with cancer. This is important because tra- 7. Extent of confidentiality of records
ditional veterinary oncology treatments, surgery, chemotherapy, 8. Compensation or therapy for injuries or adverse events
and radiation therapy, are expensive and costs are prohibitive for 9. Contact person for the study
10. Voluntary participation and right to withdraw
some clients. Clinical trial enrollment may present an opportu- 11. Termination of participation by the principal investigator
nity to help some clients who may not have the financial means 12. Unforeseen risks
to pursue treatment or receive care for their pet, or provide treat- 13. Financial obligations
ment to those pets that have progressed in the face of traditional 14. Hospital review committee contact person
therapies. When all medical options are described to clients as
far as care for their pet’s disease, some may choose clinical trials Modified with permission from Morris Animal Foundation: www.morrisanimalfoundation.org.
to make an impact for future pets or people with cancer. This
altruism (by proxy) drives the decision-making process for many
caregivers. Some veterinary hospitals also have Clinical Review Boards that
Informed consent defines a trial’s purpose and the require- function similarly to human IRBs as described previously. In
ments for the client to return with their pet for future follow-up some cases, pet dogs are receiving “first in dog” drugs and AEs
procedures/appointments, and is required for all patients to enroll are expected, with grade V events (fatality) possible. Although this
in a clinical trial. This consent is a written acknowledgment, cre- would be predicted to reflect what is seen in an aged and ill cancer
ated by a trial’s PIs and signed by a client, of the possible positive population, it is an important element to be detailed in informed
and conversely AEs (known or unknown) of an investigational consent. The grading and reporting of AEs in clinical trials include
agent. Goals for clinical trials must be clearly outlined so true uniform common toxicity criteria for AEs (e.g., VCOG-CTCAE
informed consent can be obtained. Although AEs outside of those version 1.1) and ethical care includes treatment for any such
10
described are always possible, informed consent ensures that cli- events. Clients also have the option to withdraw their pets from
ents understand that in many trials the outcome/side effects are a clinical trial at any time without penalty. All of these provisions
as yet unknown. Ethical considerations also require rigorous are designed to ensure safety for trial participants and the ethical
informed consent of study procedures, especially in biologically conduct of clinical research.
intensive trials, because repeated invasive procedures or even serial
imaging may result in the false perception of a stronger therapeu- Trial Reporting
tic intent. 93 The transparent reporting of clinical trials has received consid-
As the treatment of companion animals with cancer is purely erable attention in the past several years. For randomized trials,
a client-driven choice, there are no true “standards of care” in the current “gold standard” guidelines for reporting of data is the
veterinary oncology. Although there are proven active regimes Consolidated Standards of Reporting Trials (CONSORT; www.
for the care of common cancers in dogs (i.e., cyclophosphamide, consort-statement.org). In these guidelines, logical and stepwise
hydroxydaunorubicin (doxorubicin), vincristine [Oncovin], and guides to the reporting of patient enrollment, patient allocation
prednisone [CHOP]-based chemotherapy in lymphoma, plati- (between and within treatment groups), patient follow-up, and
num or anthracyclines in OSA), these therapies are not required. data analysis are clearly spelled out. Anyone devising, performing,
Therefore veterinary and comparative oncology trials can offer and indeed critically appraising clinical trials should be well versed
investigational therapies in naïve disease. Clinical trials can ran- in these guidelines.
domize patients to placebo arms if there is an interest in compar-
ing a novel therapy to no therapy. Although, as in human trials, Conclusions
informed consent must clearly state the inclusion of a placebo
arm, the protocol design may include an allowance for crossover Clinical trials are an important research discipline to improve care
to study drug or traditional therapies either at a defined interval or and outcome for cancer patients in both human and veterinary
in documented progressive disease. Requirements for early stop- oncology. Steps should be made to ensure study aims are achiev-
ping rules can also alleviate some of these ethical concerns when able within a crafted study design and protocol. Rules governing
94
overt drug inactivity or activity is evident. Box 18.1 defines the design are prospective and involve questions of dose and schedule
suggested elements that should be included in any clinical trial selection, toxicity, activity, and comparison to known effective
informed consent document. 1 therapies. Statistical expertise is also necessary to ensure appropri-
Many regulatory safeguards have been put in place to promote ate clinical trial design. Regulatory oversight of veterinary oncol-
the welfare and interests of animals used in biomedical and clini- ogy trials is increasing, and new approval of veterinary oncology
cal research. Protocols to use animal subjects in clinical research agents will emphasize these processes over the next decade. Com-
must be approved by Institutional Animal Care and Use Commit- parative oncology trials also are key to the inclusion of pet ani-
tees (IACUCs), and these bodies are also involved in oversight of mals in the evaluation of novel anticancer therapeutics, imaging
research study conduct to ensure ethical standards are maintained. strategies, and medical devices. Consortia groups will continue to